From Memora Health (Dr. Flyckt and Dr. Colbert), San Francisco, CA; and Harvard Medical School (Dr. Colbert), Boston, MA.

A close relative was recently diagnosed with follicular lymphoma. He was cared for at a high-ranked cancer center by physicians with demonstrated expertise, and even had the support of a care navigator. Still, he was often left feeling overwhelmed and confused, holding an inch-thick stack of papers, instructions, and pamphlets. As he left his treatment planning visit, reeling from the emotional burden of his diagnosis and all the unfamiliar terminology, he didn’t know what to do or what to expect. Later, when he experienced early signs of tumor lysis syndrome, he struggled to reach his care team for triage and guidance. When he went to the emergency room, his oncologist was never informed.

This scenario is unfortunately common, and versions of this scenario play out thousands of times each day across the US health system. Within the clinic and hospital setting, patients receive excellent care from their providers, but a disconnect emerges once the patient leaves these medical settings: patients at home struggle to find guidance and support, while care teams lack the tools to engage patients between visits or monitor their health across care settings, providers, or episodes of care.

Leveraging Technology to Move From Episodes of Care to Complex Care Journeys

The use of automated messaging, artificial intelligence and natural language processing–driven chat experiences, and text-based support is becoming more common. However, health care lags behind other industries in the adoption of these technologies.^1,2 The slow pace can be warranted, given that health care is more complicated and higher risk than inquiring about a lost package, ordering groceries, or applying for a mortgage. At the same time, many of the consumer engagement tools used to guide an applicant through the multiple steps and complexities of their home loan process or to prompt viewers to select new shows to binge have applications in health care.

Over the past few years, technologies have emerged that guide patients through complex care journeys and allow care teams to monitor and engage patients between visits. These solutions come in different formats, but generally patients can receive messages on their phones that contain disease-specific educational content, prompts to fill prescriptions and take medications, and reminders and guidance on how to prepare for appointments and procedures. These programs also collect relevant data from patients through survey and electronic patient-reported outcomes instruments, as well as connected patient monitoring devices, that help track patient progress and identify issues as they arise. Many programs also incorporate symptom triage pathways and use natural language processing to respond automatically to patient questions and concerns.^3,4

These technology solutions can automate many tasks that in the past required a care team member to spend hours on the phone. Newly freed from such repetitive tasks, care teams can now focus on more in-depth interactions with those patients who are most in need—the types of interactions that are more satisfying and rewarding. Such assistance is particularly needed today with the staffing shortages faced by most health systems.⁵

In addition, technology allows teams to see the panel of patients they are caring for and to quickly identify and take action on any specific needs or issues. Care teams can focus on any patient and see where they are in their journey. When appropriate, some solutions also allow care teams to engage directly with patients through text-messaging, creating a seamless experience and unified communication channel. Ideally, these solutions should be linked or embedded within the electronic health record or other primary system of record, so that teams can easily access these tools through their existing workflows and avoid creating yet another interface to navigate.

The Impact of Low-Tech Solutions to Deliver High-Touch Support

There is evidence showing that digital patient navigation tools impact patient care. In the oncology setting, patients with a digital navigator have achieved over 95% adherence rates with complex oral chemotherapy regimens (Memora Health Unpublished Data. 2022.). In the postpartum setting, a text message–based program improved screening rates for postpartum depression and did so with very high patient satisfaction ratings.⁶ Particularly notable is the fact that this depression screening program achieved these results in a population that was predominantly low income, with more than half belonging to underrepresented minority populations.⁶

We believe these digital patient navigation technologies, specifically low-tech solutions that don’t require app downloads, portal log-ins, or high-speed internet, will transform care delivery over the next 5 to 10 years. Successful management of complex conditions like diabetes or cancer requires more than 3 hours of care each day,⁷ yet most patients spend only 1 or 2 hours per month directly interacting with their health care providers. However, most patients carry their phones with them at all times, and artificial intelligence–enabled text support is “always on” to provide support, monitoring, and guidance, wherever a patient happens to be when assistance is needed.

Shifting the Model to Support a Lifetime of Care

While still in the early stages of development, these tools have the potential to radically alter the practice of medicine, shifting the focus from episodic interactions to continuous journey-based care delivery. Outside of an acute event bringing a patient into the clinic or emergency room, many patients go a year or more without seeing their primary care providers.⁸ During that time, an immense amount of information is underreported or completely lost. Capturing this information in real-time and more holistically over a person’s lifetime of care could provide physicians better insight to both better manage and more fully evaluate the success of treatment plans by tracking patient symptoms, pain, and functional status over time. With this more longitudinal view of the patient, we see a pathway towards achieving the Quadruple Aim: patients who are more supported will achieve better outcomes at lower cost, they will have a better experience, and care teams will be empowered to focus their time on more satisfying activities rather than repetitive administrative tasks.

Corresponding author: James A. Colbert, MD, MBA; [email protected]

Disclosures: Dr. Flyckt and Dr. Colbert are employed by Memora Health, an organization that helps health care systems digitize and automate care journeys.

From Memora Health (Dr. Flyckt and Dr. Colbert), San Francisco, CA; and Harvard Medical School (Dr. Colbert), Boston, MA.

A close relative was recently diagnosed with follicular lymphoma. He was cared for at a high-ranked cancer center by physicians with demonstrated expertise, and even had the support of a care navigator. Still, he was often left feeling overwhelmed and confused, holding an inch-thick stack of papers, instructions, and pamphlets. As he left his treatment planning visit, reeling from the emotional burden of his diagnosis and all the unfamiliar terminology, he didn’t know what to do or what to expect. Later, when he experienced early signs of tumor lysis syndrome, he struggled to reach his care team for triage and guidance. When he went to the emergency room, his oncologist was never informed.

This scenario is unfortunately common, and versions of this scenario play out thousands of times each day across the US health system. Within the clinic and hospital setting, patients receive excellent care from their providers, but a disconnect emerges once the patient leaves these medical settings: patients at home struggle to find guidance and support, while care teams lack the tools to engage patients between visits or monitor their health across care settings, providers, or episodes of care.

Leveraging Technology to Move From Episodes of Care to Complex Care Journeys

The use of automated messaging, artificial intelligence and natural language processing–driven chat experiences, and text-based support is becoming more common. However, health care lags behind other industries in the adoption of these technologies.^1,2 The slow pace can be warranted, given that health care is more complicated and higher risk than inquiring about a lost package, ordering groceries, or applying for a mortgage. At the same time, many of the consumer engagement tools used to guide an applicant through the multiple steps and complexities of their home loan process or to prompt viewers to select new shows to binge have applications in health care.

Over the past few years, technologies have emerged that guide patients through complex care journeys and allow care teams to monitor and engage patients between visits. These solutions come in different formats, but generally patients can receive messages on their phones that contain disease-specific educational content, prompts to fill prescriptions and take medications, and reminders and guidance on how to prepare for appointments and procedures. These programs also collect relevant data from patients through survey and electronic patient-reported outcomes instruments, as well as connected patient monitoring devices, that help track patient progress and identify issues as they arise. Many programs also incorporate symptom triage pathways and use natural language processing to respond automatically to patient questions and concerns.^3,4

These technology solutions can automate many tasks that in the past required a care team member to spend hours on the phone. Newly freed from such repetitive tasks, care teams can now focus on more in-depth interactions with those patients who are most in need—the types of interactions that are more satisfying and rewarding. Such assistance is particularly needed today with the staffing shortages faced by most health systems.⁵

In addition, technology allows teams to see the panel of patients they are caring for and to quickly identify and take action on any specific needs or issues. Care teams can focus on any patient and see where they are in their journey. When appropriate, some solutions also allow care teams to engage directly with patients through text-messaging, creating a seamless experience and unified communication channel. Ideally, these solutions should be linked or embedded within the electronic health record or other primary system of record, so that teams can easily access these tools through their existing workflows and avoid creating yet another interface to navigate.

The Impact of Low-Tech Solutions to Deliver High-Touch Support

There is evidence showing that digital patient navigation tools impact patient care. In the oncology setting, patients with a digital navigator have achieved over 95% adherence rates with complex oral chemotherapy regimens (Memora Health Unpublished Data. 2022.). In the postpartum setting, a text message–based program improved screening rates for postpartum depression and did so with very high patient satisfaction ratings.⁶ Particularly notable is the fact that this depression screening program achieved these results in a population that was predominantly low income, with more than half belonging to underrepresented minority populations.⁶

We believe these digital patient navigation technologies, specifically low-tech solutions that don’t require app downloads, portal log-ins, or high-speed internet, will transform care delivery over the next 5 to 10 years. Successful management of complex conditions like diabetes or cancer requires more than 3 hours of care each day,⁷ yet most patients spend only 1 or 2 hours per month directly interacting with their health care providers. However, most patients carry their phones with them at all times, and artificial intelligence–enabled text support is “always on” to provide support, monitoring, and guidance, wherever a patient happens to be when assistance is needed.

Shifting the Model to Support a Lifetime of Care

While still in the early stages of development, these tools have the potential to radically alter the practice of medicine, shifting the focus from episodic interactions to continuous journey-based care delivery. Outside of an acute event bringing a patient into the clinic or emergency room, many patients go a year or more without seeing their primary care providers.⁸ During that time, an immense amount of information is underreported or completely lost. Capturing this information in real-time and more holistically over a person’s lifetime of care could provide physicians better insight to both better manage and more fully evaluate the success of treatment plans by tracking patient symptoms, pain, and functional status over time. With this more longitudinal view of the patient, we see a pathway towards achieving the Quadruple Aim: patients who are more supported will achieve better outcomes at lower cost, they will have a better experience, and care teams will be empowered to focus their time on more satisfying activities rather than repetitive administrative tasks.

Corresponding author: James A. Colbert, MD, MBA; [email protected]

Disclosures: Dr. Flyckt and Dr. Colbert are employed by Memora Health, an organization that helps health care systems digitize and automate care journeys.

From Memora Health (Dr. Flyckt and Dr. Colbert), San Francisco, CA; and Harvard Medical School (Dr. Colbert), Boston, MA.

A close relative was recently diagnosed with follicular lymphoma. He was cared for at a high-ranked cancer center by physicians with demonstrated expertise, and even had the support of a care navigator. Still, he was often left feeling overwhelmed and confused, holding an inch-thick stack of papers, instructions, and pamphlets. As he left his treatment planning visit, reeling from the emotional burden of his diagnosis and all the unfamiliar terminology, he didn’t know what to do or what to expect. Later, when he experienced early signs of tumor lysis syndrome, he struggled to reach his care team for triage and guidance. When he went to the emergency room, his oncologist was never informed.

This scenario is unfortunately common, and versions of this scenario play out thousands of times each day across the US health system. Within the clinic and hospital setting, patients receive excellent care from their providers, but a disconnect emerges once the patient leaves these medical settings: patients at home struggle to find guidance and support, while care teams lack the tools to engage patients between visits or monitor their health across care settings, providers, or episodes of care.

Leveraging Technology to Move From Episodes of Care to Complex Care Journeys

The use of automated messaging, artificial intelligence and natural language processing–driven chat experiences, and text-based support is becoming more common. However, health care lags behind other industries in the adoption of these technologies.^1,2 The slow pace can be warranted, given that health care is more complicated and higher risk than inquiring about a lost package, ordering groceries, or applying for a mortgage. At the same time, many of the consumer engagement tools used to guide an applicant through the multiple steps and complexities of their home loan process or to prompt viewers to select new shows to binge have applications in health care.

Over the past few years, technologies have emerged that guide patients through complex care journeys and allow care teams to monitor and engage patients between visits. These solutions come in different formats, but generally patients can receive messages on their phones that contain disease-specific educational content, prompts to fill prescriptions and take medications, and reminders and guidance on how to prepare for appointments and procedures. These programs also collect relevant data from patients through survey and electronic patient-reported outcomes instruments, as well as connected patient monitoring devices, that help track patient progress and identify issues as they arise. Many programs also incorporate symptom triage pathways and use natural language processing to respond automatically to patient questions and concerns.^3,4

These technology solutions can automate many tasks that in the past required a care team member to spend hours on the phone. Newly freed from such repetitive tasks, care teams can now focus on more in-depth interactions with those patients who are most in need—the types of interactions that are more satisfying and rewarding. Such assistance is particularly needed today with the staffing shortages faced by most health systems.⁵

In addition, technology allows teams to see the panel of patients they are caring for and to quickly identify and take action on any specific needs or issues. Care teams can focus on any patient and see where they are in their journey. When appropriate, some solutions also allow care teams to engage directly with patients through text-messaging, creating a seamless experience and unified communication channel. Ideally, these solutions should be linked or embedded within the electronic health record or other primary system of record, so that teams can easily access these tools through their existing workflows and avoid creating yet another interface to navigate.

The Impact of Low-Tech Solutions to Deliver High-Touch Support

There is evidence showing that digital patient navigation tools impact patient care. In the oncology setting, patients with a digital navigator have achieved over 95% adherence rates with complex oral chemotherapy regimens (Memora Health Unpublished Data. 2022.). In the postpartum setting, a text message–based program improved screening rates for postpartum depression and did so with very high patient satisfaction ratings.⁶ Particularly notable is the fact that this depression screening program achieved these results in a population that was predominantly low income, with more than half belonging to underrepresented minority populations.⁶

We believe these digital patient navigation technologies, specifically low-tech solutions that don’t require app downloads, portal log-ins, or high-speed internet, will transform care delivery over the next 5 to 10 years. Successful management of complex conditions like diabetes or cancer requires more than 3 hours of care each day,⁷ yet most patients spend only 1 or 2 hours per month directly interacting with their health care providers. However, most patients carry their phones with them at all times, and artificial intelligence–enabled text support is “always on” to provide support, monitoring, and guidance, wherever a patient happens to be when assistance is needed.

Shifting the Model to Support a Lifetime of Care

While still in the early stages of development, these tools have the potential to radically alter the practice of medicine, shifting the focus from episodic interactions to continuous journey-based care delivery. Outside of an acute event bringing a patient into the clinic or emergency room, many patients go a year or more without seeing their primary care providers.⁸ During that time, an immense amount of information is underreported or completely lost. Capturing this information in real-time and more holistically over a person’s lifetime of care could provide physicians better insight to both better manage and more fully evaluate the success of treatment plans by tracking patient symptoms, pain, and functional status over time. With this more longitudinal view of the patient, we see a pathway towards achieving the Quadruple Aim: patients who are more supported will achieve better outcomes at lower cost, they will have a better experience, and care teams will be empowered to focus their time on more satisfying activities rather than repetitive administrative tasks.

Corresponding author: James A. Colbert, MD, MBA; [email protected]

Disclosures: Dr. Flyckt and Dr. Colbert are employed by Memora Health, an organization that helps health care systems digitize and automate care journeys.

This issue of the Journal of Clinical Outcomes (JCOM) debuts a new cover design that brings forward the articles and features in each issue. Although the Journal’s cover has a new look, JCOM’s goals remain the same—improving care by disseminating evidence of quality improvement in health care and sharing access to the medical literature with our readers. We continue our mission to promote the best medical practice by providing clinicians with updates and communicating advances that lead to measurable improvement in health care delivery, quality, and outcomes.

As we continue the work of improving health care quality, knowledge gaps and unmet needs in the literature remain. These unmet needs are evident throughout all phases of health care delivery. Moreover, the Institutes of Medicine report that centered on efforts to build a safer health care environment by redesigning health care processes remains salient.¹ The journey to continuous improvement in health care, where we achieve threshold change in the quality of each process and across the entire health care system, requires collective effort. Such efforts include establishing clear metrics and measurements for improvement goals throughout the patient’s journey through diagnosis, treatment, transitions of care, and disease management.^2,3 To address evidence and knowledge gaps in the literature, JCOM publishes reports of original studies and quality improvement projects as well as reviews, providing its 30,000 readers with new evidence to implement in daily practice. We welcome submissions of original research reports, reports of quality improvement projects that follow the SQUIRE 2.0 standards,⁴ and perspectives on developments and innovations in health care delivery.

The next chapter in health care delivery improvement will encompass value-based care.⁵ This new era of clinical outcomes management will dictate the metrics and outcomes reporting⁶ and how to plan future investments. The value-based phase will increase innovation and shape policies that advance population health, transforming every step in the care delivery journey.⁷ The next phase in health care delivery will also create a viable financial structure while implementing effective performance measures for optimal outcomes through patient-centered care and optimization of cost and care strategies. In light of health care’s evolution toward a value-based model, JCOM welcomes submissions of manuscripts that explore themes central to this model, including patient-centered care, implementation of best practices, system design, safety, cost-effectiveness, and the balance between cost optimization and quality. For JCOM’s authors and readers, our editorial team remains commited to the highest standards in timely publishing to support our community through our collective expertise and dedication to quality improvement.

Corresponding author: Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA; [email protected]

This issue of the Journal of Clinical Outcomes (JCOM) debuts a new cover design that brings forward the articles and features in each issue. Although the Journal’s cover has a new look, JCOM’s goals remain the same—improving care by disseminating evidence of quality improvement in health care and sharing access to the medical literature with our readers. We continue our mission to promote the best medical practice by providing clinicians with updates and communicating advances that lead to measurable improvement in health care delivery, quality, and outcomes.

As we continue the work of improving health care quality, knowledge gaps and unmet needs in the literature remain. These unmet needs are evident throughout all phases of health care delivery. Moreover, the Institutes of Medicine report that centered on efforts to build a safer health care environment by redesigning health care processes remains salient.¹ The journey to continuous improvement in health care, where we achieve threshold change in the quality of each process and across the entire health care system, requires collective effort. Such efforts include establishing clear metrics and measurements for improvement goals throughout the patient’s journey through diagnosis, treatment, transitions of care, and disease management.^2,3 To address evidence and knowledge gaps in the literature, JCOM publishes reports of original studies and quality improvement projects as well as reviews, providing its 30,000 readers with new evidence to implement in daily practice. We welcome submissions of original research reports, reports of quality improvement projects that follow the SQUIRE 2.0 standards,⁴ and perspectives on developments and innovations in health care delivery.

The next chapter in health care delivery improvement will encompass value-based care.⁵ This new era of clinical outcomes management will dictate the metrics and outcomes reporting⁶ and how to plan future investments. The value-based phase will increase innovation and shape policies that advance population health, transforming every step in the care delivery journey.⁷ The next phase in health care delivery will also create a viable financial structure while implementing effective performance measures for optimal outcomes through patient-centered care and optimization of cost and care strategies. In light of health care’s evolution toward a value-based model, JCOM welcomes submissions of manuscripts that explore themes central to this model, including patient-centered care, implementation of best practices, system design, safety, cost-effectiveness, and the balance between cost optimization and quality. For JCOM’s authors and readers, our editorial team remains commited to the highest standards in timely publishing to support our community through our collective expertise and dedication to quality improvement.

Corresponding author: Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA; [email protected]

This issue of the Journal of Clinical Outcomes (JCOM) debuts a new cover design that brings forward the articles and features in each issue. Although the Journal’s cover has a new look, JCOM’s goals remain the same—improving care by disseminating evidence of quality improvement in health care and sharing access to the medical literature with our readers. We continue our mission to promote the best medical practice by providing clinicians with updates and communicating advances that lead to measurable improvement in health care delivery, quality, and outcomes.

As we continue the work of improving health care quality, knowledge gaps and unmet needs in the literature remain. These unmet needs are evident throughout all phases of health care delivery. Moreover, the Institutes of Medicine report that centered on efforts to build a safer health care environment by redesigning health care processes remains salient.¹ The journey to continuous improvement in health care, where we achieve threshold change in the quality of each process and across the entire health care system, requires collective effort. Such efforts include establishing clear metrics and measurements for improvement goals throughout the patient’s journey through diagnosis, treatment, transitions of care, and disease management.^2,3 To address evidence and knowledge gaps in the literature, JCOM publishes reports of original studies and quality improvement projects as well as reviews, providing its 30,000 readers with new evidence to implement in daily practice. We welcome submissions of original research reports, reports of quality improvement projects that follow the SQUIRE 2.0 standards,⁴ and perspectives on developments and innovations in health care delivery.

The next chapter in health care delivery improvement will encompass value-based care.⁵ This new era of clinical outcomes management will dictate the metrics and outcomes reporting⁶ and how to plan future investments. The value-based phase will increase innovation and shape policies that advance population health, transforming every step in the care delivery journey.⁷ The next phase in health care delivery will also create a viable financial structure while implementing effective performance measures for optimal outcomes through patient-centered care and optimization of cost and care strategies. In light of health care’s evolution toward a value-based model, JCOM welcomes submissions of manuscripts that explore themes central to this model, including patient-centered care, implementation of best practices, system design, safety, cost-effectiveness, and the balance between cost optimization and quality. For JCOM’s authors and readers, our editorial team remains commited to the highest standards in timely publishing to support our community through our collective expertise and dedication to quality improvement.

Corresponding author: Ebrahim Barkoudah, MD, MPH, Department of Medicine, Brigham and Women’s Hospital, Boston, MA; [email protected]

Study 1 Overview (Park et al)

Objective: To examine whether implementation of a geriatric trauma clinical pathway is associated with reduced rates of delirium in older adults with traumatic injury.

Design: Retrospective case-control study of electronic health records.

Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and did not undergo an operation. A Geriatric Trauma Care Pathway was developed by a multidisciplinary Stanford Quality Pathways team and formally launched on November 1, 2018. The clinical pathway was designed to incorporate geriatric best practices, which included order sets (eg, age-appropriate nonpharmacological interventions and pharmacological dosages), guidelines (eg, Institute for Healthcare Improvement Age-Friendly Health systems 4M framework), automated consultations (comprehensive geriatric assessment), and escalation pathways executed by a multidisciplinary team (eg, pain, bowel, and sleep regulation). The clinical pathway began with admission to the emergency department (ED) (ie, automatic trigger of geriatric trauma care admission order set), daily multidisciplinary team meetings during acute hospitalization, and a transitional care team consultation for postdischarge follow-up or home visit.

Main outcome measures: The primary outcome was delirium as determined by a positive Confusion Assessment Method (CAM) score or a diagnosis of delirium by the clinical team. The secondary outcome was hospital length of stay (LOS). Process measures for pathway compliance (eg, achieving adequate pain control, early mobilization, advance care planning) were assessed. Outcome measures were compared between patients who underwent the Geriatric Trauma Care Pathway intervention (postimplementation group) vs patients who were treated prior to pathway implementation (baseline pre-implementation group).

Main results: Of the 859 eligible patients, 712 were included in the analysis (442 [62.1%] in the baseline pre-implementation group and 270 [37.9%] in the postimplementation group); mean (SD) age was 81.4 (9.1) years, and 394 (55.3%) were women. The injury mechanism was similar between groups, with falls being the most common cause of injury (247 [55.9%] in the baseline group vs 162 [60.0%] in the postimplementation group; P = .43). Injuries as measured by Injury Severity Score (ISS) were minor or moderate in both groups (261 [59.0%] in baseline group vs 168 [62.2%] in postimplementation group; P = .87). The adjusted odds ratio (OR) for delirium in the postimplementation group was lower compared to the baseline pre-implementation group (OR, 0.54; 95% CI, 0.37-0.80; P < .001). Measures of advance care planning in the postimplementation group improved, including more frequent goals-of-care documentation (53.7% in postimplementation group vs 16.7% in baseline group; P < .001) and a shortened time to first goals-of-care discussion upon presenting to the ED (36 hours in postimplementation group vs 50 hours in baseline group; P = .03).

Conclusion: Implementation of a multidisciplinary geriatric trauma clinical pathway for older adults with traumatic injury at a single level I trauma center was associated with reduced rates of delirium.

Study 2 Overview (Bryant et al)

Objective: To determine whether an interdisciplinary care pathway for frail trauma patients can improve in-hospital mortality, complications, and 30-day readmissions.

Design: Retrospective cohort study of frail patients.

Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and survived more than 24 hours; admitted to and discharged from the trauma unit; and determined to be pre-frail or frail by a geriatrician’s assessment. A Frailty Identification and Care Pathway designed to reduce delirium and complications in frail older trauma patients was developed by a multidisciplinary team and implemented in 2016. The standardized evidence-based interdisciplinary care pathway included utilization of order sets and interventions for delirium prevention, early ambulation, bowel and pain regimens, nutrition and physical therapy consults, medication management, care-goal setting, and geriatric assessments.

Main outcome measures: The main outcomes were delirium as determined by a positive CAM score, major complications as defined by the Trauma Quality Improvement Project, in-hospital mortality, and 30-day hospital readmission. Outcome measures were compared between patients who underwent Frailty Identification and Care Pathway intervention (postintervention group) vs patients who were treated prior to pathway implementation (pre-intervention group).

Main results: A total of 269 frail patients were included in the analysis (125 in pre-intervention group vs 144 in postintervention group). Patient demographic and admission characteristics were similar between the 2 groups: mean age was 83.5 (7.1) years, 60.6% were women, and median ISS was 10 (interquartile range [IQR], 9-14). The injury mechanism was similar between groups, with falls accounting for 92.8% and 86.1% of injuries in the pre-intervention and postintervention groups, respectively (P = .07). In univariate analysis, the Frailty Identification and Care Pathway intervention was associated with a significant reduction in delirium (12.5% vs 21.6%, P = .04) and 30-day hospital readmission (2.7% vs 9.6%, P = .01) compared to patients in the pre-intervention group. However, rates of major complications (28.5% vs 28.0%, P = 0.93) and in-hospital mortality (4.2% vs 7.2%, P = .28) were similar between the pre-intervention and postintervention groups. In multivariate logistic regression models adjusted for patient characteristics (age, sex, race, ISS), patients in the postintervention group had lower delirium (OR, 0.44; 95% CI, 0.22-0.88; P = .02) and 30-day hospital readmission (OR, 0.25; 95% CI, 0.07-0.84; P = .02) rates compared to those in the pre-intervention group.

Conclusion: Implementation of an interdisciplinary care protocol for frail geriatric trauma patients significantly decreased their risks for in-hospital delirium and 30-day hospital readmission.

Commentary

Traumatic injuries in older adults are associated with higher morbidity and mortality compared to younger patients, with falls and motor vehicle accidents accounting for a majority of these injuries. Astoundingly, up to one-third of this vulnerable population presenting to hospitals with an ISS greater than 15 may die during hospitalization.¹ As a result, a large number of studies and clinical trials have focused on interventions that are designed to reduce fall risks, and hence reduce adverse consequences of traumatic injuries that may arise after falls.² However, this emphasis on falls prevention has overshadowed a need to develop effective geriatric-centered clinical interventions that aim to improve outcomes in older adults who present to hospitals with traumatic injuries. Furthermore, frailty—a geriatric syndrome indicative of an increased state of vulnerability and predictive of adverse outcomes such as delirium—is highly prevalent in older patients with traumatic injury.³ Thus, there is an urgent need to develop novel, hospital-based, traumatic injury–targeting strategies that incorporate a thoughtful redesign of the care framework that includes evidence-based interventions for geriatric syndromes such as delirium and frailty.

The study reported by Park et al (Study 1) represents the latest effort to evaluate inpatient management strategies designed to improve outcomes in hospitalized older adults who have sustained traumatic injury. Through the implementation of a novel multidisciplinary Geriatric Trauma Care Pathway that incorporates geriatric best practices, this intervention was found to be associated with a 46% lower risk of in-hospital delirium. Because of the inclusion of all age-eligible patients across all strata of traumatic injuries, rather than preselecting for those at the highest risk for poor clinical outcomes, the benefits of this intervention extend to those with minor or moderate injury severity. Furthermore, the improvement in delirium (ie, the primary outcome) is particularly meaningful given that delirium is one of the most common hospital-associated complications that increase hospital LOS, discharge to an institution, and mortality in older adults. Finally, the study’s observed reduced time to a first goals-of-care discussion and increased frequency of goals-of-care documentation after intervention should not be overlooked. The improvements in these 2 process measures are highly significant given that advanced care planning, an intervention that helps to align patients’ values, goals, and treatments, is completed at substantially lower rates in older adults in the acute hospital setting.⁴

Similarly, in an earlier published study, Bryant and colleagues (Study 2) also show that a geriatric-focused interdisciplinary trauma care pathway is associated with delirium risk reduction in hospitalized older trauma patients. Much like Study 1, the Frailty Identification and Care Pathway utilized in Study 2 is an evidence-based interdisciplinary care pathway that includes the use of geriatric assessments, order sets, and geriatric best practices. Moreover, its exclusive inclusion of pre-frail and frail older patients (ie, those at higher risk for poor outcomes) with moderate injury severity (median ISS of 10 [IQR, 9-14]) suggests that this type of care pathway benefits hospitalized older trauma patients, who are particularly vulnerable to adverse complications such as delirium. Moreover, the successful utilization of the FRAIL questionnaire, a validated frailty screening tool, by surgical residents in the ED to initiate this care pathway demonstrates the feasibility of its use in expediting frailty screening in older patients in trauma care.

Application for Clinical Practice and System Implementation

Findings from the 2 studies discussed in this review indicate that implementation of interdisciplinary clinical care pathways predicated on evidence-based geriatric principles and best practices is a promising approach to reduce delirium in hospitalized older trauma patients. These studies have helped to lay the groundwork in outlining the roadmaps (eg, processes and infrastructures) needed to create such clinical pathways. These key elements include: (1) integration of a multidisciplinary committee (eg, representation from trauma, emergency, and geriatric medicine, nursing, physical and occupational therapy, pharmacy, social work) in pathway design and implementation; (2) adaption of evidence-based geriatric best practices (eg, the Institute for Healthcare Improvement Age-Friendly Health System 4M framework [medication, mentation, mobility, what matters]) to prioritize interventions and to design a pathway that incorporates these features; (3) incorporation of comprehensive geriatric assessment by interdisciplinary providers; (4) utilization of validated clinical instruments to assess physical and cognitive functions, frailty, delirium, and social determinants of health; (5) modification of electronic health record systems to encompass order sets that incorporate evidence-based, nonpharmacological and pharmacological interventions to manage symptoms (eg, delirium, pain, bowel movement, sleep, immobility, polypharmacy) essential to quality geriatric care; and (6) integration of patient and caregiver preferences via goals-of-care discussions and corresponding documentation and communication of these goals.

Additionally, these 2 studies imparted some strategies that may facilitate the implementation of interdisciplinary clinical care pathways in trauma care. Examples of such facilitators include: (1) collaboration with champions within each specialty to reinforce education and buy-in; (2) creation of automatically triggered order sets upon patient presentation to the ED that unites distinct features of clinical pathways; (3) adaption and reorganization of existing hospital infrastructures and resources to meet the needs of clinical pathways implementation (eg, utilizing information technology resources to develop electronic health record order sets; using quality department to develop clinical pathway guidelines and electronic outcome dashboards); and (4) development of individualized patient and caregiver education materials based on care needs (eg, principles of delirium prevention and preservation of mobility during hospitalization) to prepare and engage these stakeholders in patient care and recovery.

Practice Points

• A geriatric interdisciplinary care model can be effectively applied to the management of acute trauma in older patients.
• Interdisciplinary clinical pathways should incorporate geriatric best practices and guidelines and age-appropriate order sets to prioritize and integrate care.

—Fred Ko, MD, MS

Study 1 Overview (Park et al)

Objective: To examine whether implementation of a geriatric trauma clinical pathway is associated with reduced rates of delirium in older adults with traumatic injury.

Design: Retrospective case-control study of electronic health records.

Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and did not undergo an operation. A Geriatric Trauma Care Pathway was developed by a multidisciplinary Stanford Quality Pathways team and formally launched on November 1, 2018. The clinical pathway was designed to incorporate geriatric best practices, which included order sets (eg, age-appropriate nonpharmacological interventions and pharmacological dosages), guidelines (eg, Institute for Healthcare Improvement Age-Friendly Health systems 4M framework), automated consultations (comprehensive geriatric assessment), and escalation pathways executed by a multidisciplinary team (eg, pain, bowel, and sleep regulation). The clinical pathway began with admission to the emergency department (ED) (ie, automatic trigger of geriatric trauma care admission order set), daily multidisciplinary team meetings during acute hospitalization, and a transitional care team consultation for postdischarge follow-up or home visit.

Main outcome measures: The primary outcome was delirium as determined by a positive Confusion Assessment Method (CAM) score or a diagnosis of delirium by the clinical team. The secondary outcome was hospital length of stay (LOS). Process measures for pathway compliance (eg, achieving adequate pain control, early mobilization, advance care planning) were assessed. Outcome measures were compared between patients who underwent the Geriatric Trauma Care Pathway intervention (postimplementation group) vs patients who were treated prior to pathway implementation (baseline pre-implementation group).

Main results: Of the 859 eligible patients, 712 were included in the analysis (442 [62.1%] in the baseline pre-implementation group and 270 [37.9%] in the postimplementation group); mean (SD) age was 81.4 (9.1) years, and 394 (55.3%) were women. The injury mechanism was similar between groups, with falls being the most common cause of injury (247 [55.9%] in the baseline group vs 162 [60.0%] in the postimplementation group; P = .43). Injuries as measured by Injury Severity Score (ISS) were minor or moderate in both groups (261 [59.0%] in baseline group vs 168 [62.2%] in postimplementation group; P = .87). The adjusted odds ratio (OR) for delirium in the postimplementation group was lower compared to the baseline pre-implementation group (OR, 0.54; 95% CI, 0.37-0.80; P < .001). Measures of advance care planning in the postimplementation group improved, including more frequent goals-of-care documentation (53.7% in postimplementation group vs 16.7% in baseline group; P < .001) and a shortened time to first goals-of-care discussion upon presenting to the ED (36 hours in postimplementation group vs 50 hours in baseline group; P = .03).

Conclusion: Implementation of a multidisciplinary geriatric trauma clinical pathway for older adults with traumatic injury at a single level I trauma center was associated with reduced rates of delirium.

Study 2 Overview (Bryant et al)

Objective: To determine whether an interdisciplinary care pathway for frail trauma patients can improve in-hospital mortality, complications, and 30-day readmissions.

Design: Retrospective cohort study of frail patients.

Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and survived more than 24 hours; admitted to and discharged from the trauma unit; and determined to be pre-frail or frail by a geriatrician’s assessment. A Frailty Identification and Care Pathway designed to reduce delirium and complications in frail older trauma patients was developed by a multidisciplinary team and implemented in 2016. The standardized evidence-based interdisciplinary care pathway included utilization of order sets and interventions for delirium prevention, early ambulation, bowel and pain regimens, nutrition and physical therapy consults, medication management, care-goal setting, and geriatric assessments.

Main outcome measures: The main outcomes were delirium as determined by a positive CAM score, major complications as defined by the Trauma Quality Improvement Project, in-hospital mortality, and 30-day hospital readmission. Outcome measures were compared between patients who underwent Frailty Identification and Care Pathway intervention (postintervention group) vs patients who were treated prior to pathway implementation (pre-intervention group).

Main results: A total of 269 frail patients were included in the analysis (125 in pre-intervention group vs 144 in postintervention group). Patient demographic and admission characteristics were similar between the 2 groups: mean age was 83.5 (7.1) years, 60.6% were women, and median ISS was 10 (interquartile range [IQR], 9-14). The injury mechanism was similar between groups, with falls accounting for 92.8% and 86.1% of injuries in the pre-intervention and postintervention groups, respectively (P = .07). In univariate analysis, the Frailty Identification and Care Pathway intervention was associated with a significant reduction in delirium (12.5% vs 21.6%, P = .04) and 30-day hospital readmission (2.7% vs 9.6%, P = .01) compared to patients in the pre-intervention group. However, rates of major complications (28.5% vs 28.0%, P = 0.93) and in-hospital mortality (4.2% vs 7.2%, P = .28) were similar between the pre-intervention and postintervention groups. In multivariate logistic regression models adjusted for patient characteristics (age, sex, race, ISS), patients in the postintervention group had lower delirium (OR, 0.44; 95% CI, 0.22-0.88; P = .02) and 30-day hospital readmission (OR, 0.25; 95% CI, 0.07-0.84; P = .02) rates compared to those in the pre-intervention group.

Conclusion: Implementation of an interdisciplinary care protocol for frail geriatric trauma patients significantly decreased their risks for in-hospital delirium and 30-day hospital readmission.

Commentary

Traumatic injuries in older adults are associated with higher morbidity and mortality compared to younger patients, with falls and motor vehicle accidents accounting for a majority of these injuries. Astoundingly, up to one-third of this vulnerable population presenting to hospitals with an ISS greater than 15 may die during hospitalization.¹ As a result, a large number of studies and clinical trials have focused on interventions that are designed to reduce fall risks, and hence reduce adverse consequences of traumatic injuries that may arise after falls.² However, this emphasis on falls prevention has overshadowed a need to develop effective geriatric-centered clinical interventions that aim to improve outcomes in older adults who present to hospitals with traumatic injuries. Furthermore, frailty—a geriatric syndrome indicative of an increased state of vulnerability and predictive of adverse outcomes such as delirium—is highly prevalent in older patients with traumatic injury.³ Thus, there is an urgent need to develop novel, hospital-based, traumatic injury–targeting strategies that incorporate a thoughtful redesign of the care framework that includes evidence-based interventions for geriatric syndromes such as delirium and frailty.

The study reported by Park et al (Study 1) represents the latest effort to evaluate inpatient management strategies designed to improve outcomes in hospitalized older adults who have sustained traumatic injury. Through the implementation of a novel multidisciplinary Geriatric Trauma Care Pathway that incorporates geriatric best practices, this intervention was found to be associated with a 46% lower risk of in-hospital delirium. Because of the inclusion of all age-eligible patients across all strata of traumatic injuries, rather than preselecting for those at the highest risk for poor clinical outcomes, the benefits of this intervention extend to those with minor or moderate injury severity. Furthermore, the improvement in delirium (ie, the primary outcome) is particularly meaningful given that delirium is one of the most common hospital-associated complications that increase hospital LOS, discharge to an institution, and mortality in older adults. Finally, the study’s observed reduced time to a first goals-of-care discussion and increased frequency of goals-of-care documentation after intervention should not be overlooked. The improvements in these 2 process measures are highly significant given that advanced care planning, an intervention that helps to align patients’ values, goals, and treatments, is completed at substantially lower rates in older adults in the acute hospital setting.⁴

Similarly, in an earlier published study, Bryant and colleagues (Study 2) also show that a geriatric-focused interdisciplinary trauma care pathway is associated with delirium risk reduction in hospitalized older trauma patients. Much like Study 1, the Frailty Identification and Care Pathway utilized in Study 2 is an evidence-based interdisciplinary care pathway that includes the use of geriatric assessments, order sets, and geriatric best practices. Moreover, its exclusive inclusion of pre-frail and frail older patients (ie, those at higher risk for poor outcomes) with moderate injury severity (median ISS of 10 [IQR, 9-14]) suggests that this type of care pathway benefits hospitalized older trauma patients, who are particularly vulnerable to adverse complications such as delirium. Moreover, the successful utilization of the FRAIL questionnaire, a validated frailty screening tool, by surgical residents in the ED to initiate this care pathway demonstrates the feasibility of its use in expediting frailty screening in older patients in trauma care.

Application for Clinical Practice and System Implementation

Findings from the 2 studies discussed in this review indicate that implementation of interdisciplinary clinical care pathways predicated on evidence-based geriatric principles and best practices is a promising approach to reduce delirium in hospitalized older trauma patients. These studies have helped to lay the groundwork in outlining the roadmaps (eg, processes and infrastructures) needed to create such clinical pathways. These key elements include: (1) integration of a multidisciplinary committee (eg, representation from trauma, emergency, and geriatric medicine, nursing, physical and occupational therapy, pharmacy, social work) in pathway design and implementation; (2) adaption of evidence-based geriatric best practices (eg, the Institute for Healthcare Improvement Age-Friendly Health System 4M framework [medication, mentation, mobility, what matters]) to prioritize interventions and to design a pathway that incorporates these features; (3) incorporation of comprehensive geriatric assessment by interdisciplinary providers; (4) utilization of validated clinical instruments to assess physical and cognitive functions, frailty, delirium, and social determinants of health; (5) modification of electronic health record systems to encompass order sets that incorporate evidence-based, nonpharmacological and pharmacological interventions to manage symptoms (eg, delirium, pain, bowel movement, sleep, immobility, polypharmacy) essential to quality geriatric care; and (6) integration of patient and caregiver preferences via goals-of-care discussions and corresponding documentation and communication of these goals.

Additionally, these 2 studies imparted some strategies that may facilitate the implementation of interdisciplinary clinical care pathways in trauma care. Examples of such facilitators include: (1) collaboration with champions within each specialty to reinforce education and buy-in; (2) creation of automatically triggered order sets upon patient presentation to the ED that unites distinct features of clinical pathways; (3) adaption and reorganization of existing hospital infrastructures and resources to meet the needs of clinical pathways implementation (eg, utilizing information technology resources to develop electronic health record order sets; using quality department to develop clinical pathway guidelines and electronic outcome dashboards); and (4) development of individualized patient and caregiver education materials based on care needs (eg, principles of delirium prevention and preservation of mobility during hospitalization) to prepare and engage these stakeholders in patient care and recovery.

Practice Points

• A geriatric interdisciplinary care model can be effectively applied to the management of acute trauma in older patients.
• Interdisciplinary clinical pathways should incorporate geriatric best practices and guidelines and age-appropriate order sets to prioritize and integrate care.

—Fred Ko, MD, MS

Study 1 Overview (Park et al)

Objective: To examine whether implementation of a geriatric trauma clinical pathway is associated with reduced rates of delirium in older adults with traumatic injury.

Design: Retrospective case-control study of electronic health records.

Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and did not undergo an operation. A Geriatric Trauma Care Pathway was developed by a multidisciplinary Stanford Quality Pathways team and formally launched on November 1, 2018. The clinical pathway was designed to incorporate geriatric best practices, which included order sets (eg, age-appropriate nonpharmacological interventions and pharmacological dosages), guidelines (eg, Institute for Healthcare Improvement Age-Friendly Health systems 4M framework), automated consultations (comprehensive geriatric assessment), and escalation pathways executed by a multidisciplinary team (eg, pain, bowel, and sleep regulation). The clinical pathway began with admission to the emergency department (ED) (ie, automatic trigger of geriatric trauma care admission order set), daily multidisciplinary team meetings during acute hospitalization, and a transitional care team consultation for postdischarge follow-up or home visit.

Main outcome measures: The primary outcome was delirium as determined by a positive Confusion Assessment Method (CAM) score or a diagnosis of delirium by the clinical team. The secondary outcome was hospital length of stay (LOS). Process measures for pathway compliance (eg, achieving adequate pain control, early mobilization, advance care planning) were assessed. Outcome measures were compared between patients who underwent the Geriatric Trauma Care Pathway intervention (postimplementation group) vs patients who were treated prior to pathway implementation (baseline pre-implementation group).

Main results: Of the 859 eligible patients, 712 were included in the analysis (442 [62.1%] in the baseline pre-implementation group and 270 [37.9%] in the postimplementation group); mean (SD) age was 81.4 (9.1) years, and 394 (55.3%) were women. The injury mechanism was similar between groups, with falls being the most common cause of injury (247 [55.9%] in the baseline group vs 162 [60.0%] in the postimplementation group; P = .43). Injuries as measured by Injury Severity Score (ISS) were minor or moderate in both groups (261 [59.0%] in baseline group vs 168 [62.2%] in postimplementation group; P = .87). The adjusted odds ratio (OR) for delirium in the postimplementation group was lower compared to the baseline pre-implementation group (OR, 0.54; 95% CI, 0.37-0.80; P < .001). Measures of advance care planning in the postimplementation group improved, including more frequent goals-of-care documentation (53.7% in postimplementation group vs 16.7% in baseline group; P < .001) and a shortened time to first goals-of-care discussion upon presenting to the ED (36 hours in postimplementation group vs 50 hours in baseline group; P = .03).

Conclusion: Implementation of a multidisciplinary geriatric trauma clinical pathway for older adults with traumatic injury at a single level I trauma center was associated with reduced rates of delirium.

Study 2 Overview (Bryant et al)

Objective: To determine whether an interdisciplinary care pathway for frail trauma patients can improve in-hospital mortality, complications, and 30-day readmissions.

Design: Retrospective cohort study of frail patients.

Setting and participants: Eligible patients were persons aged 65 years or older who were admitted to the trauma service and survived more than 24 hours; admitted to and discharged from the trauma unit; and determined to be pre-frail or frail by a geriatrician’s assessment. A Frailty Identification and Care Pathway designed to reduce delirium and complications in frail older trauma patients was developed by a multidisciplinary team and implemented in 2016. The standardized evidence-based interdisciplinary care pathway included utilization of order sets and interventions for delirium prevention, early ambulation, bowel and pain regimens, nutrition and physical therapy consults, medication management, care-goal setting, and geriatric assessments.

Main outcome measures: The main outcomes were delirium as determined by a positive CAM score, major complications as defined by the Trauma Quality Improvement Project, in-hospital mortality, and 30-day hospital readmission. Outcome measures were compared between patients who underwent Frailty Identification and Care Pathway intervention (postintervention group) vs patients who were treated prior to pathway implementation (pre-intervention group).

Main results: A total of 269 frail patients were included in the analysis (125 in pre-intervention group vs 144 in postintervention group). Patient demographic and admission characteristics were similar between the 2 groups: mean age was 83.5 (7.1) years, 60.6% were women, and median ISS was 10 (interquartile range [IQR], 9-14). The injury mechanism was similar between groups, with falls accounting for 92.8% and 86.1% of injuries in the pre-intervention and postintervention groups, respectively (P = .07). In univariate analysis, the Frailty Identification and Care Pathway intervention was associated with a significant reduction in delirium (12.5% vs 21.6%, P = .04) and 30-day hospital readmission (2.7% vs 9.6%, P = .01) compared to patients in the pre-intervention group. However, rates of major complications (28.5% vs 28.0%, P = 0.93) and in-hospital mortality (4.2% vs 7.2%, P = .28) were similar between the pre-intervention and postintervention groups. In multivariate logistic regression models adjusted for patient characteristics (age, sex, race, ISS), patients in the postintervention group had lower delirium (OR, 0.44; 95% CI, 0.22-0.88; P = .02) and 30-day hospital readmission (OR, 0.25; 95% CI, 0.07-0.84; P = .02) rates compared to those in the pre-intervention group.

Conclusion: Implementation of an interdisciplinary care protocol for frail geriatric trauma patients significantly decreased their risks for in-hospital delirium and 30-day hospital readmission.

Commentary

Traumatic injuries in older adults are associated with higher morbidity and mortality compared to younger patients, with falls and motor vehicle accidents accounting for a majority of these injuries. Astoundingly, up to one-third of this vulnerable population presenting to hospitals with an ISS greater than 15 may die during hospitalization.¹ As a result, a large number of studies and clinical trials have focused on interventions that are designed to reduce fall risks, and hence reduce adverse consequences of traumatic injuries that may arise after falls.² However, this emphasis on falls prevention has overshadowed a need to develop effective geriatric-centered clinical interventions that aim to improve outcomes in older adults who present to hospitals with traumatic injuries. Furthermore, frailty—a geriatric syndrome indicative of an increased state of vulnerability and predictive of adverse outcomes such as delirium—is highly prevalent in older patients with traumatic injury.³ Thus, there is an urgent need to develop novel, hospital-based, traumatic injury–targeting strategies that incorporate a thoughtful redesign of the care framework that includes evidence-based interventions for geriatric syndromes such as delirium and frailty.

The study reported by Park et al (Study 1) represents the latest effort to evaluate inpatient management strategies designed to improve outcomes in hospitalized older adults who have sustained traumatic injury. Through the implementation of a novel multidisciplinary Geriatric Trauma Care Pathway that incorporates geriatric best practices, this intervention was found to be associated with a 46% lower risk of in-hospital delirium. Because of the inclusion of all age-eligible patients across all strata of traumatic injuries, rather than preselecting for those at the highest risk for poor clinical outcomes, the benefits of this intervention extend to those with minor or moderate injury severity. Furthermore, the improvement in delirium (ie, the primary outcome) is particularly meaningful given that delirium is one of the most common hospital-associated complications that increase hospital LOS, discharge to an institution, and mortality in older adults. Finally, the study’s observed reduced time to a first goals-of-care discussion and increased frequency of goals-of-care documentation after intervention should not be overlooked. The improvements in these 2 process measures are highly significant given that advanced care planning, an intervention that helps to align patients’ values, goals, and treatments, is completed at substantially lower rates in older adults in the acute hospital setting.⁴

Similarly, in an earlier published study, Bryant and colleagues (Study 2) also show that a geriatric-focused interdisciplinary trauma care pathway is associated with delirium risk reduction in hospitalized older trauma patients. Much like Study 1, the Frailty Identification and Care Pathway utilized in Study 2 is an evidence-based interdisciplinary care pathway that includes the use of geriatric assessments, order sets, and geriatric best practices. Moreover, its exclusive inclusion of pre-frail and frail older patients (ie, those at higher risk for poor outcomes) with moderate injury severity (median ISS of 10 [IQR, 9-14]) suggests that this type of care pathway benefits hospitalized older trauma patients, who are particularly vulnerable to adverse complications such as delirium. Moreover, the successful utilization of the FRAIL questionnaire, a validated frailty screening tool, by surgical residents in the ED to initiate this care pathway demonstrates the feasibility of its use in expediting frailty screening in older patients in trauma care.

Application for Clinical Practice and System Implementation

Findings from the 2 studies discussed in this review indicate that implementation of interdisciplinary clinical care pathways predicated on evidence-based geriatric principles and best practices is a promising approach to reduce delirium in hospitalized older trauma patients. These studies have helped to lay the groundwork in outlining the roadmaps (eg, processes and infrastructures) needed to create such clinical pathways. These key elements include: (1) integration of a multidisciplinary committee (eg, representation from trauma, emergency, and geriatric medicine, nursing, physical and occupational therapy, pharmacy, social work) in pathway design and implementation; (2) adaption of evidence-based geriatric best practices (eg, the Institute for Healthcare Improvement Age-Friendly Health System 4M framework [medication, mentation, mobility, what matters]) to prioritize interventions and to design a pathway that incorporates these features; (3) incorporation of comprehensive geriatric assessment by interdisciplinary providers; (4) utilization of validated clinical instruments to assess physical and cognitive functions, frailty, delirium, and social determinants of health; (5) modification of electronic health record systems to encompass order sets that incorporate evidence-based, nonpharmacological and pharmacological interventions to manage symptoms (eg, delirium, pain, bowel movement, sleep, immobility, polypharmacy) essential to quality geriatric care; and (6) integration of patient and caregiver preferences via goals-of-care discussions and corresponding documentation and communication of these goals.

Additionally, these 2 studies imparted some strategies that may facilitate the implementation of interdisciplinary clinical care pathways in trauma care. Examples of such facilitators include: (1) collaboration with champions within each specialty to reinforce education and buy-in; (2) creation of automatically triggered order sets upon patient presentation to the ED that unites distinct features of clinical pathways; (3) adaption and reorganization of existing hospital infrastructures and resources to meet the needs of clinical pathways implementation (eg, utilizing information technology resources to develop electronic health record order sets; using quality department to develop clinical pathway guidelines and electronic outcome dashboards); and (4) development of individualized patient and caregiver education materials based on care needs (eg, principles of delirium prevention and preservation of mobility during hospitalization) to prepare and engage these stakeholders in patient care and recovery.

Practice Points

• A geriatric interdisciplinary care model can be effectively applied to the management of acute trauma in older patients.
• Interdisciplinary clinical pathways should incorporate geriatric best practices and guidelines and age-appropriate order sets to prioritize and integrate care.

—Fred Ko, MD, MS

Study 1 Overview (Cortés et al)

Objective: To compare the efficacy and safety of trastuzumab deruxtecan with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane.

Design: Phase 3, multicenter, open-label randomized trial conducted at 169 centers and 15 countries.

Setting and participants: Eligible patients had to have unresectable or metastatic HER2-positive breast cancer that had progressed during or after treatment with trastuzumab and a taxane or had disease that progressed within 6 months after neoadjuvant or adjuvant treatment involving trastuzumab or taxane. Patients with stable or previously treated brain metastases were eligible. Patients were not eligible for the study if they had symptomatic brain metastases, prior exposure to trastuzumab emtansine, or a history of interstitial lung disease.

Intervention: Patients were randomized in a 1-to-1 fashion to receive either trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or trastuzumab emtansine 3.6 mg/kg every 3 weeks. Patients were stratified according to hormone-receptor status, prior treatment with epratuzumab, and the presence or absence of visceral disease.

Main outcome measures: The primary endpoint of the study was progression-free survival as determined by an independent central review. Secondary endpoints included overall survival, overall response, and safety.

Main results: A total of 524 patients were enrolled in the study, with 261 patients randomized to trastuzumab deruxtecan and 263 patients randomized to trastuzumab emtansine. The demographic and baseline characteristics were similar between the 2 cohorts, and 60% of patients in both groups received prior epratuzumab therapy. Stable brain metastases were present in around 20% of patients in each group, and 70% of patients in each group had visceral disease. The median duration of follow-up was 16.2 months with trastuzumab deruxtecan and 15.3 months with trastuzumab emtansine.

The median progression-free survival was not reached in the trastuzumab deruxtecan group and was 6.8 months in the trastuzumab emtansine group (95% CI, 5.6-8.2). At 12 months the percentage of patients alive without disease progression was significantly larger in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. The hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22-0.37; P < .001). Subgroup analyses showed a benefit in progression-free survival with trastuzumab deruxtecan across all subgroups.

At the time of this analysis, the percentage of patients who were alive at 12 months was 94% with trastuzumab deruxtecan and 85.9% with trastuzumab emtansine. The response rates were significantly higher with trastuzumab deruxtecan compared with trastuzumab emtansine (79.7% vs 34.2%). A complete response was seen in 16% of patients in the trastuzumab deruxtecan arm, compared with 8.7% of patients in the trastuzumab emtansine group. The disease control rate (complete response, partial response, or stable disease) was higher in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group (96.6% vs 76.8%).

Serious adverse events were reported in 19% of patients in the trastuzumab deruxtecan group and 18% of patients in the trastuzumab emtansine group. Discontinuation due to adverse events was higher in the trastuzumab deruxtecan group, with 13.6% of patients discontinuing trastuzumab deruxtecan. Grade 3 or higher adverse events were seen in 52% of patients treated with trastuzumab deruxtecan and 48% of patients treated with trastuzumab emtansine. The most commonly reported adverse event with trastuzumab deruxtecan was nausea/vomiting and fatigue. These adverse events were seen more in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. No drug-related grade 5 adverse events were reported.

In the trastuzumab deruxtecan group, 10.5% of patients receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis. Seven patients had grade 1 events, 18 patients had grade 2 events, and 2 patients had grade 3 events. No grade 4 or 5 events were noted in either treatment group. The median time to onset of interstitial lung disease or pneumonitis in those receiving trastuzumab deruxtecan was 168 days (range, 33-507). Discontinuation of therapy due to interstitial lung disease or pneumonitis occurred in 8% of patients receiving trastuzumab deruxtecan and 1% of patients receiving trastuzumab emtansine.

Conclusion: Trastuzumab deruxtecan significantly decreases the risk of disease progression or death compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and taxane-based therapy.

Study 2 Overview (Modi et al)

Objective: To assess the efficacy of trastuzumab deruxtecan in patients with unresectable or metastatic breast cancer with low levels of HER2 expression.

Design: This was a randomized, 2-group, open-label, phase 3 trial.

Setting and participants: The trial was designed with a planned enrollment of 480 patients with hormone receptor–positive disease and 60 patients with hormone receptor–negative disease. Patients were randomized in a 2:1 ratio. Randomization was stratified according to HER2 status (immunohistochemical [IHC] 1+ vs IHC 2+/in situ hybridization [ISH] negative), number of prior lines of therapy, and hormone-receptor status. IHC scores for HER2 expression were determined through central testing. Specimens that had HER2 IHC scores of 2+ were reflexed to ISH. Specimens were considered HER2-low-expressing if they had an IHC score of 1+ or if they had an IHC score of 2+ and were ISH negative.

Eligible patients had to have received chemotherapy for metastatic disease or had disease recurrence during or within 6 months after completing adjuvant chemotherapy. Patients with hormone receptor–positive disease must have had at least 1 line of endocrine therapy. Patients were eligible if they had stable brain metastases. Patients with interstitial lung disease were excluded.

Intervention: Patients were randomized to receive trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).

Main outcome measures: The primary endpoint was progression-free survival in patients with hormone receptor–positive disease. Secondary endpoints were progression-free survival among all patients, overall survival in hormone receptor–positive patients, and overall survival in all patients. Additional secondary endpoints included objective response rates, duration of response, and efficacy in hormone receptor–negative patients.

Main results: A total of 373 patients were assigned to the trastuzumab deruxtecan group and 184 patients were assigned to the physician’s choice chemotherapy group; 88% of patients in each cohort were hormone receptor–positive. In the physician’s choice chemotherapy group, 51% received eribulin, 20% received capecitabine, 10% received nab-paclitaxel, 10% received gemcitabine, and 8% received paclitaxel. The demographic and baseline characteristics were similar between both cohorts. The median duration of follow-up was 18.4 months.

The median progression-free survival in the hormone receptor–positive cohort was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice chemotherapy group (HR, 0.51; 95% CI, 0.4-0.64). Subgroup analyses revealed a benefit across all subgroups. The median progression-free survival among patients with a HER2 IHC score of 1+ and those with a HER2 IHC score of 2+/negative ISH were identical. In patients who received a prior CDK 4/6 inhibitor, the median progression-free survival was also 10 months in the trastuzumab deruxtecan group. In those who were CDK 4/6- naïve, the progression-free survival was 11.7 months. The progression-free survival in all patients was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice chemotherapy group (HR, 0.46; 95% CI, 0.24-0.89).

The median overall survival in the hormone receptor–positive cohort was 23.9 months in the trastuzumab deruxtecan group compared with 17.5 months in the physician’s choice chemotherapy group (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median overall survival in the entire population was 23.4 months in the trastuzumab deruxtecan group vs 16.8 months in the physician’s choice chemotherapy group. In the hormone receptor–negative cohort, the median overall survival was 18.2 months in the trastuzumab deruxtecan group and 8.3 months in the physician’s choice chemotherapy group. Complete responses were seen in 3.6% in the trastuzumab deruxtecan group and 0.6% and the physician’s choice chemotherapy group. The median duration of response was 10.7 months in the trastuzumab deruxtecan group and 6.8 months in the physician’s choice chemotherapy group.

Incidence of serious adverse events was 27% in the trastuzumab deruxtecan group and 25% in the physician’s choice chemotherapy group. Grade 3 or higher events occurred in 52% of the trastuzumab deruxtecan group and 67% of the physician’s choice chemotherapy group. Discontinuation due to adverse events occurred in 16% in the trastuzumab deruxtecan group and 18% in the physician’s choice chemotherapy group; 14 patients in the trastuzumab deruxtecan group and 5 patients in the physician’s choice chemotherapy group had an adverse event that was associated with death. Death due to pneumonitis in the trastuzumab deruxtecan group occurred in 2 patients. Drug-related interstitial lung disease or pneumonitis occurred in 45 patients who received trastuzumab deruxtecan. The majority of these events were grade 1 and grade 2. However, 3 patients had grade 5 interstitial lung disease or pneumonitis.

Conclusion: Treatment with trastuzumab deruxtecan led to a significant improvement in progression-free survival compared to physician’s choice chemotherapy in patients with HER2-low metastatic breast cancer.

Commentary

Trastuzumab deruxtecan is an antibody drug conjugate that consists of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase 1 inhibitor. This antibody drug conjugate is unique compared with prior antibody drug conjugates such as trastuzumab emtansine in that it has a high drug-to-antibody ratio (~8). Furthermore, there appears to be a unique bystander effect resulting in off-target cytotoxicity to neighboring tumor cells, enhancing the efficacy of this novel therapy. Prior studies of trastuzumab deruxtecan have shown durable activity in heavily pretreated patients with metastatic HER2-positive breast cancer.¹

HER2-positive breast cancer represents approximately 20% of breast cancer cases in women.² Historically, HER2 positivity has been defined by strong HER2 expression with IHC staining (ie, score 3+) or HER2 amplification through ISH. Conversely, HER2-negative disease has historically been defined as those with IHC scores of 0 or 1+. This group represents approximately 60% of HER2-negative metastatic breast cancer patients.³ These patients have limited targeted treatment options after progressing on primary therapy. Prior data has shown that patients with low HER2 expression represent a heterogeneous population and thus, the historic categorization of HER2 status as positive or negative may in fact not adequately characterize the proportion of patients who may derive clinical benefit from HER2-directed therapies. Nevertheless, there have been no data to date that have shown improved outcomes in low HER2 expressers with anti-HER2 therapies.

The current studies add to the rapidly growing body of literature outlining the efficacy of the novel antibody drug conjugate trastuzumab deruxtecan. The implications of the data presented in these 2 studies are immediately practice changing.

In the DESTINY-Breast03 trial, Cortéz and colleagues show that trastuzumab deruxtecan therapy significantly prolongs progression-free survival compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on first-line trastuzumab and taxane-based therapy. With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in this trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer. The overall survival in this trial was immature at the time of this analysis, and thus continued follow-up to validate the results noted here are warranted.

The DESTINY-Breast04 trial by Modi et al expands the cohort of patients who benefit from trastuzumab deruxtecan profoundly. This study defines a population of patients with HER2-low metastatic breast cancer who will now be eligible for HER2-directed therapies. These data show that therapy with trastuzumab deruxtecan leads to a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy in patients with metastatic breast cancer with low expression of HER2. This benefit was seen in both the estrogen receptor–positive cohort as well as the entire population, including pre-treated triple-negative disease. Furthermore, this study does not define a threshold of HER2 expression by IHC that predicts benefit with trastuzumab deruxtecan. Patients with an IHC score of 1+ as well as those with a score of 2+/ISH negative both benefit to a similar extent from trastuzumab deruxtecan. Interestingly, in the DAISY trial, antitumor activity was noted with trastuzumab deruxtecan even in those without any detectable HER2 expression on IHC.⁴ Given the inconsistency and potential false negatives of IHC along with heterogeneous HER2 expression, further work is needed to better identify patients with low levels of HER2 expression who may benefit from this novel antibody drug conjugate. Thus, a reliable test to quantitatively assess the level of HER2 expression is needed in order to determine more accurately which patients will benefit from trastuzumab deruxtecan.

Last, trastuzumab deruxtecan has been associated with interstitial lung disease and pneumonitis. Interstitial lung disease and pneumonitis occurred in approximately 10% of patients who received trastuzumab deruxtecan in the DESTINY-Breast03 trial and about 12% of patients in the DESTINY-Breast04 trial. Most of these events were grade 1 and grade 2. Nevertheless, clinicians must be aware of this risk and monitor patients frequently for the development of pneumonitis or interstitial lung disease.

Application for Clinical Practice and System Implementation

The results of the current studies show a longer progression-free survival with trastuzumab deruxtecan in both HER2-low expressing metastatic breast cancer and HER2-positive metastatic breast cancer following taxane and trastuzumab-based therapy. These results are clearly practice changing and represent a new standard of care in these patient populations. It is incumbent upon treating oncologists to work with our pathology colleagues to assess HER2 IHC thoroughly in order to identify all potential patients who may benefit from trastuzumab deruxtecan in the metastatic setting. The continued advancement of anti-HER2 therapy will undoubtedly have a significant impact on patient outcomes going forward.

Practice Points

• With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in the DESTINY-Breast03 trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer.
• In the DESTINY-Breast04 trial, a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy was seen in patients with metastatic breast cancer with low expression of HER2, including both the estrogen receptor–positive cohort as well as the entire population, including those with pre-treated triple-negative disease.

­—Daniel Isaac, DO, MS

Study 1 Overview (Cortés et al)

Objective: To compare the efficacy and safety of trastuzumab deruxtecan with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane.

Design: Phase 3, multicenter, open-label randomized trial conducted at 169 centers and 15 countries.

Setting and participants: Eligible patients had to have unresectable or metastatic HER2-positive breast cancer that had progressed during or after treatment with trastuzumab and a taxane or had disease that progressed within 6 months after neoadjuvant or adjuvant treatment involving trastuzumab or taxane. Patients with stable or previously treated brain metastases were eligible. Patients were not eligible for the study if they had symptomatic brain metastases, prior exposure to trastuzumab emtansine, or a history of interstitial lung disease.

Intervention: Patients were randomized in a 1-to-1 fashion to receive either trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or trastuzumab emtansine 3.6 mg/kg every 3 weeks. Patients were stratified according to hormone-receptor status, prior treatment with epratuzumab, and the presence or absence of visceral disease.

Main outcome measures: The primary endpoint of the study was progression-free survival as determined by an independent central review. Secondary endpoints included overall survival, overall response, and safety.

Main results: A total of 524 patients were enrolled in the study, with 261 patients randomized to trastuzumab deruxtecan and 263 patients randomized to trastuzumab emtansine. The demographic and baseline characteristics were similar between the 2 cohorts, and 60% of patients in both groups received prior epratuzumab therapy. Stable brain metastases were present in around 20% of patients in each group, and 70% of patients in each group had visceral disease. The median duration of follow-up was 16.2 months with trastuzumab deruxtecan and 15.3 months with trastuzumab emtansine.

The median progression-free survival was not reached in the trastuzumab deruxtecan group and was 6.8 months in the trastuzumab emtansine group (95% CI, 5.6-8.2). At 12 months the percentage of patients alive without disease progression was significantly larger in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. The hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22-0.37; P < .001). Subgroup analyses showed a benefit in progression-free survival with trastuzumab deruxtecan across all subgroups.

At the time of this analysis, the percentage of patients who were alive at 12 months was 94% with trastuzumab deruxtecan and 85.9% with trastuzumab emtansine. The response rates were significantly higher with trastuzumab deruxtecan compared with trastuzumab emtansine (79.7% vs 34.2%). A complete response was seen in 16% of patients in the trastuzumab deruxtecan arm, compared with 8.7% of patients in the trastuzumab emtansine group. The disease control rate (complete response, partial response, or stable disease) was higher in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group (96.6% vs 76.8%).

Serious adverse events were reported in 19% of patients in the trastuzumab deruxtecan group and 18% of patients in the trastuzumab emtansine group. Discontinuation due to adverse events was higher in the trastuzumab deruxtecan group, with 13.6% of patients discontinuing trastuzumab deruxtecan. Grade 3 or higher adverse events were seen in 52% of patients treated with trastuzumab deruxtecan and 48% of patients treated with trastuzumab emtansine. The most commonly reported adverse event with trastuzumab deruxtecan was nausea/vomiting and fatigue. These adverse events were seen more in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. No drug-related grade 5 adverse events were reported.

In the trastuzumab deruxtecan group, 10.5% of patients receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis. Seven patients had grade 1 events, 18 patients had grade 2 events, and 2 patients had grade 3 events. No grade 4 or 5 events were noted in either treatment group. The median time to onset of interstitial lung disease or pneumonitis in those receiving trastuzumab deruxtecan was 168 days (range, 33-507). Discontinuation of therapy due to interstitial lung disease or pneumonitis occurred in 8% of patients receiving trastuzumab deruxtecan and 1% of patients receiving trastuzumab emtansine.

Conclusion: Trastuzumab deruxtecan significantly decreases the risk of disease progression or death compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and taxane-based therapy.

Study 2 Overview (Modi et al)

Objective: To assess the efficacy of trastuzumab deruxtecan in patients with unresectable or metastatic breast cancer with low levels of HER2 expression.

Design: This was a randomized, 2-group, open-label, phase 3 trial.

Setting and participants: The trial was designed with a planned enrollment of 480 patients with hormone receptor–positive disease and 60 patients with hormone receptor–negative disease. Patients were randomized in a 2:1 ratio. Randomization was stratified according to HER2 status (immunohistochemical [IHC] 1+ vs IHC 2+/in situ hybridization [ISH] negative), number of prior lines of therapy, and hormone-receptor status. IHC scores for HER2 expression were determined through central testing. Specimens that had HER2 IHC scores of 2+ were reflexed to ISH. Specimens were considered HER2-low-expressing if they had an IHC score of 1+ or if they had an IHC score of 2+ and were ISH negative.

Eligible patients had to have received chemotherapy for metastatic disease or had disease recurrence during or within 6 months after completing adjuvant chemotherapy. Patients with hormone receptor–positive disease must have had at least 1 line of endocrine therapy. Patients were eligible if they had stable brain metastases. Patients with interstitial lung disease were excluded.

Intervention: Patients were randomized to receive trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).

Main outcome measures: The primary endpoint was progression-free survival in patients with hormone receptor–positive disease. Secondary endpoints were progression-free survival among all patients, overall survival in hormone receptor–positive patients, and overall survival in all patients. Additional secondary endpoints included objective response rates, duration of response, and efficacy in hormone receptor–negative patients.

Main results: A total of 373 patients were assigned to the trastuzumab deruxtecan group and 184 patients were assigned to the physician’s choice chemotherapy group; 88% of patients in each cohort were hormone receptor–positive. In the physician’s choice chemotherapy group, 51% received eribulin, 20% received capecitabine, 10% received nab-paclitaxel, 10% received gemcitabine, and 8% received paclitaxel. The demographic and baseline characteristics were similar between both cohorts. The median duration of follow-up was 18.4 months.

The median progression-free survival in the hormone receptor–positive cohort was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice chemotherapy group (HR, 0.51; 95% CI, 0.4-0.64). Subgroup analyses revealed a benefit across all subgroups. The median progression-free survival among patients with a HER2 IHC score of 1+ and those with a HER2 IHC score of 2+/negative ISH were identical. In patients who received a prior CDK 4/6 inhibitor, the median progression-free survival was also 10 months in the trastuzumab deruxtecan group. In those who were CDK 4/6- naïve, the progression-free survival was 11.7 months. The progression-free survival in all patients was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice chemotherapy group (HR, 0.46; 95% CI, 0.24-0.89).

The median overall survival in the hormone receptor–positive cohort was 23.9 months in the trastuzumab deruxtecan group compared with 17.5 months in the physician’s choice chemotherapy group (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median overall survival in the entire population was 23.4 months in the trastuzumab deruxtecan group vs 16.8 months in the physician’s choice chemotherapy group. In the hormone receptor–negative cohort, the median overall survival was 18.2 months in the trastuzumab deruxtecan group and 8.3 months in the physician’s choice chemotherapy group. Complete responses were seen in 3.6% in the trastuzumab deruxtecan group and 0.6% and the physician’s choice chemotherapy group. The median duration of response was 10.7 months in the trastuzumab deruxtecan group and 6.8 months in the physician’s choice chemotherapy group.

Incidence of serious adverse events was 27% in the trastuzumab deruxtecan group and 25% in the physician’s choice chemotherapy group. Grade 3 or higher events occurred in 52% of the trastuzumab deruxtecan group and 67% of the physician’s choice chemotherapy group. Discontinuation due to adverse events occurred in 16% in the trastuzumab deruxtecan group and 18% in the physician’s choice chemotherapy group; 14 patients in the trastuzumab deruxtecan group and 5 patients in the physician’s choice chemotherapy group had an adverse event that was associated with death. Death due to pneumonitis in the trastuzumab deruxtecan group occurred in 2 patients. Drug-related interstitial lung disease or pneumonitis occurred in 45 patients who received trastuzumab deruxtecan. The majority of these events were grade 1 and grade 2. However, 3 patients had grade 5 interstitial lung disease or pneumonitis.

Conclusion: Treatment with trastuzumab deruxtecan led to a significant improvement in progression-free survival compared to physician’s choice chemotherapy in patients with HER2-low metastatic breast cancer.

Commentary

Trastuzumab deruxtecan is an antibody drug conjugate that consists of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase 1 inhibitor. This antibody drug conjugate is unique compared with prior antibody drug conjugates such as trastuzumab emtansine in that it has a high drug-to-antibody ratio (~8). Furthermore, there appears to be a unique bystander effect resulting in off-target cytotoxicity to neighboring tumor cells, enhancing the efficacy of this novel therapy. Prior studies of trastuzumab deruxtecan have shown durable activity in heavily pretreated patients with metastatic HER2-positive breast cancer.¹

HER2-positive breast cancer represents approximately 20% of breast cancer cases in women.² Historically, HER2 positivity has been defined by strong HER2 expression with IHC staining (ie, score 3+) or HER2 amplification through ISH. Conversely, HER2-negative disease has historically been defined as those with IHC scores of 0 or 1+. This group represents approximately 60% of HER2-negative metastatic breast cancer patients.³ These patients have limited targeted treatment options after progressing on primary therapy. Prior data has shown that patients with low HER2 expression represent a heterogeneous population and thus, the historic categorization of HER2 status as positive or negative may in fact not adequately characterize the proportion of patients who may derive clinical benefit from HER2-directed therapies. Nevertheless, there have been no data to date that have shown improved outcomes in low HER2 expressers with anti-HER2 therapies.

The current studies add to the rapidly growing body of literature outlining the efficacy of the novel antibody drug conjugate trastuzumab deruxtecan. The implications of the data presented in these 2 studies are immediately practice changing.

In the DESTINY-Breast03 trial, Cortéz and colleagues show that trastuzumab deruxtecan therapy significantly prolongs progression-free survival compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on first-line trastuzumab and taxane-based therapy. With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in this trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer. The overall survival in this trial was immature at the time of this analysis, and thus continued follow-up to validate the results noted here are warranted.

The DESTINY-Breast04 trial by Modi et al expands the cohort of patients who benefit from trastuzumab deruxtecan profoundly. This study defines a population of patients with HER2-low metastatic breast cancer who will now be eligible for HER2-directed therapies. These data show that therapy with trastuzumab deruxtecan leads to a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy in patients with metastatic breast cancer with low expression of HER2. This benefit was seen in both the estrogen receptor–positive cohort as well as the entire population, including pre-treated triple-negative disease. Furthermore, this study does not define a threshold of HER2 expression by IHC that predicts benefit with trastuzumab deruxtecan. Patients with an IHC score of 1+ as well as those with a score of 2+/ISH negative both benefit to a similar extent from trastuzumab deruxtecan. Interestingly, in the DAISY trial, antitumor activity was noted with trastuzumab deruxtecan even in those without any detectable HER2 expression on IHC.⁴ Given the inconsistency and potential false negatives of IHC along with heterogeneous HER2 expression, further work is needed to better identify patients with low levels of HER2 expression who may benefit from this novel antibody drug conjugate. Thus, a reliable test to quantitatively assess the level of HER2 expression is needed in order to determine more accurately which patients will benefit from trastuzumab deruxtecan.

Last, trastuzumab deruxtecan has been associated with interstitial lung disease and pneumonitis. Interstitial lung disease and pneumonitis occurred in approximately 10% of patients who received trastuzumab deruxtecan in the DESTINY-Breast03 trial and about 12% of patients in the DESTINY-Breast04 trial. Most of these events were grade 1 and grade 2. Nevertheless, clinicians must be aware of this risk and monitor patients frequently for the development of pneumonitis or interstitial lung disease.

Application for Clinical Practice and System Implementation

The results of the current studies show a longer progression-free survival with trastuzumab deruxtecan in both HER2-low expressing metastatic breast cancer and HER2-positive metastatic breast cancer following taxane and trastuzumab-based therapy. These results are clearly practice changing and represent a new standard of care in these patient populations. It is incumbent upon treating oncologists to work with our pathology colleagues to assess HER2 IHC thoroughly in order to identify all potential patients who may benefit from trastuzumab deruxtecan in the metastatic setting. The continued advancement of anti-HER2 therapy will undoubtedly have a significant impact on patient outcomes going forward.

Practice Points

• With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in the DESTINY-Breast03 trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer.
• In the DESTINY-Breast04 trial, a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy was seen in patients with metastatic breast cancer with low expression of HER2, including both the estrogen receptor–positive cohort as well as the entire population, including those with pre-treated triple-negative disease.

­—Daniel Isaac, DO, MS

Study 1 Overview (Cortés et al)

Objective: To compare the efficacy and safety of trastuzumab deruxtecan with those of trastuzumab emtansine in patients with HER2-positive metastatic breast cancer previously treated with trastuzumab and taxane.

Design: Phase 3, multicenter, open-label randomized trial conducted at 169 centers and 15 countries.

Setting and participants: Eligible patients had to have unresectable or metastatic HER2-positive breast cancer that had progressed during or after treatment with trastuzumab and a taxane or had disease that progressed within 6 months after neoadjuvant or adjuvant treatment involving trastuzumab or taxane. Patients with stable or previously treated brain metastases were eligible. Patients were not eligible for the study if they had symptomatic brain metastases, prior exposure to trastuzumab emtansine, or a history of interstitial lung disease.

Intervention: Patients were randomized in a 1-to-1 fashion to receive either trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or trastuzumab emtansine 3.6 mg/kg every 3 weeks. Patients were stratified according to hormone-receptor status, prior treatment with epratuzumab, and the presence or absence of visceral disease.

Main outcome measures: The primary endpoint of the study was progression-free survival as determined by an independent central review. Secondary endpoints included overall survival, overall response, and safety.

Main results: A total of 524 patients were enrolled in the study, with 261 patients randomized to trastuzumab deruxtecan and 263 patients randomized to trastuzumab emtansine. The demographic and baseline characteristics were similar between the 2 cohorts, and 60% of patients in both groups received prior epratuzumab therapy. Stable brain metastases were present in around 20% of patients in each group, and 70% of patients in each group had visceral disease. The median duration of follow-up was 16.2 months with trastuzumab deruxtecan and 15.3 months with trastuzumab emtansine.

The median progression-free survival was not reached in the trastuzumab deruxtecan group and was 6.8 months in the trastuzumab emtansine group (95% CI, 5.6-8.2). At 12 months the percentage of patients alive without disease progression was significantly larger in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. The hazard ratio for disease progression or death from any cause was 0.28 (95% CI, 0.22-0.37; P < .001). Subgroup analyses showed a benefit in progression-free survival with trastuzumab deruxtecan across all subgroups.

At the time of this analysis, the percentage of patients who were alive at 12 months was 94% with trastuzumab deruxtecan and 85.9% with trastuzumab emtansine. The response rates were significantly higher with trastuzumab deruxtecan compared with trastuzumab emtansine (79.7% vs 34.2%). A complete response was seen in 16% of patients in the trastuzumab deruxtecan arm, compared with 8.7% of patients in the trastuzumab emtansine group. The disease control rate (complete response, partial response, or stable disease) was higher in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group (96.6% vs 76.8%).

Serious adverse events were reported in 19% of patients in the trastuzumab deruxtecan group and 18% of patients in the trastuzumab emtansine group. Discontinuation due to adverse events was higher in the trastuzumab deruxtecan group, with 13.6% of patients discontinuing trastuzumab deruxtecan. Grade 3 or higher adverse events were seen in 52% of patients treated with trastuzumab deruxtecan and 48% of patients treated with trastuzumab emtansine. The most commonly reported adverse event with trastuzumab deruxtecan was nausea/vomiting and fatigue. These adverse events were seen more in the trastuzumab deruxtecan group compared with the trastuzumab emtansine group. No drug-related grade 5 adverse events were reported.

In the trastuzumab deruxtecan group, 10.5% of patients receiving trastuzumab deruxtecan developed interstitial lung disease or pneumonitis. Seven patients had grade 1 events, 18 patients had grade 2 events, and 2 patients had grade 3 events. No grade 4 or 5 events were noted in either treatment group. The median time to onset of interstitial lung disease or pneumonitis in those receiving trastuzumab deruxtecan was 168 days (range, 33-507). Discontinuation of therapy due to interstitial lung disease or pneumonitis occurred in 8% of patients receiving trastuzumab deruxtecan and 1% of patients receiving trastuzumab emtansine.

Conclusion: Trastuzumab deruxtecan significantly decreases the risk of disease progression or death compared to trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on prior trastuzumab and taxane-based therapy.

Study 2 Overview (Modi et al)

Objective: To assess the efficacy of trastuzumab deruxtecan in patients with unresectable or metastatic breast cancer with low levels of HER2 expression.

Design: This was a randomized, 2-group, open-label, phase 3 trial.

Setting and participants: The trial was designed with a planned enrollment of 480 patients with hormone receptor–positive disease and 60 patients with hormone receptor–negative disease. Patients were randomized in a 2:1 ratio. Randomization was stratified according to HER2 status (immunohistochemical [IHC] 1+ vs IHC 2+/in situ hybridization [ISH] negative), number of prior lines of therapy, and hormone-receptor status. IHC scores for HER2 expression were determined through central testing. Specimens that had HER2 IHC scores of 2+ were reflexed to ISH. Specimens were considered HER2-low-expressing if they had an IHC score of 1+ or if they had an IHC score of 2+ and were ISH negative.

Eligible patients had to have received chemotherapy for metastatic disease or had disease recurrence during or within 6 months after completing adjuvant chemotherapy. Patients with hormone receptor–positive disease must have had at least 1 line of endocrine therapy. Patients were eligible if they had stable brain metastases. Patients with interstitial lung disease were excluded.

Intervention: Patients were randomized to receive trastuzumab deruxtecan 5.4 mg/kg every 3 weeks or physician’s choice of chemotherapy (capecitabine, eribulin, gemcitabine, paclitaxel, or nab-paclitaxel).

Main outcome measures: The primary endpoint was progression-free survival in patients with hormone receptor–positive disease. Secondary endpoints were progression-free survival among all patients, overall survival in hormone receptor–positive patients, and overall survival in all patients. Additional secondary endpoints included objective response rates, duration of response, and efficacy in hormone receptor–negative patients.

Main results: A total of 373 patients were assigned to the trastuzumab deruxtecan group and 184 patients were assigned to the physician’s choice chemotherapy group; 88% of patients in each cohort were hormone receptor–positive. In the physician’s choice chemotherapy group, 51% received eribulin, 20% received capecitabine, 10% received nab-paclitaxel, 10% received gemcitabine, and 8% received paclitaxel. The demographic and baseline characteristics were similar between both cohorts. The median duration of follow-up was 18.4 months.

The median progression-free survival in the hormone receptor–positive cohort was 10.1 months in the trastuzumab deruxtecan group and 5.4 months in the physician’s choice chemotherapy group (HR, 0.51; 95% CI, 0.4-0.64). Subgroup analyses revealed a benefit across all subgroups. The median progression-free survival among patients with a HER2 IHC score of 1+ and those with a HER2 IHC score of 2+/negative ISH were identical. In patients who received a prior CDK 4/6 inhibitor, the median progression-free survival was also 10 months in the trastuzumab deruxtecan group. In those who were CDK 4/6- naïve, the progression-free survival was 11.7 months. The progression-free survival in all patients was 9.9 months in the trastuzumab deruxtecan group and 5.1 months in the physician’s choice chemotherapy group (HR, 0.46; 95% CI, 0.24-0.89).

The median overall survival in the hormone receptor–positive cohort was 23.9 months in the trastuzumab deruxtecan group compared with 17.5 months in the physician’s choice chemotherapy group (HR, 0.64; 95% CI, 0.48-0.86; P = .003). The median overall survival in the entire population was 23.4 months in the trastuzumab deruxtecan group vs 16.8 months in the physician’s choice chemotherapy group. In the hormone receptor–negative cohort, the median overall survival was 18.2 months in the trastuzumab deruxtecan group and 8.3 months in the physician’s choice chemotherapy group. Complete responses were seen in 3.6% in the trastuzumab deruxtecan group and 0.6% and the physician’s choice chemotherapy group. The median duration of response was 10.7 months in the trastuzumab deruxtecan group and 6.8 months in the physician’s choice chemotherapy group.

Incidence of serious adverse events was 27% in the trastuzumab deruxtecan group and 25% in the physician’s choice chemotherapy group. Grade 3 or higher events occurred in 52% of the trastuzumab deruxtecan group and 67% of the physician’s choice chemotherapy group. Discontinuation due to adverse events occurred in 16% in the trastuzumab deruxtecan group and 18% in the physician’s choice chemotherapy group; 14 patients in the trastuzumab deruxtecan group and 5 patients in the physician’s choice chemotherapy group had an adverse event that was associated with death. Death due to pneumonitis in the trastuzumab deruxtecan group occurred in 2 patients. Drug-related interstitial lung disease or pneumonitis occurred in 45 patients who received trastuzumab deruxtecan. The majority of these events were grade 1 and grade 2. However, 3 patients had grade 5 interstitial lung disease or pneumonitis.

Conclusion: Treatment with trastuzumab deruxtecan led to a significant improvement in progression-free survival compared to physician’s choice chemotherapy in patients with HER2-low metastatic breast cancer.

Commentary

Trastuzumab deruxtecan is an antibody drug conjugate that consists of a humanized anti-HER2 monoclonal antibody linked to a topoisomerase 1 inhibitor. This antibody drug conjugate is unique compared with prior antibody drug conjugates such as trastuzumab emtansine in that it has a high drug-to-antibody ratio (~8). Furthermore, there appears to be a unique bystander effect resulting in off-target cytotoxicity to neighboring tumor cells, enhancing the efficacy of this novel therapy. Prior studies of trastuzumab deruxtecan have shown durable activity in heavily pretreated patients with metastatic HER2-positive breast cancer.¹

HER2-positive breast cancer represents approximately 20% of breast cancer cases in women.² Historically, HER2 positivity has been defined by strong HER2 expression with IHC staining (ie, score 3+) or HER2 amplification through ISH. Conversely, HER2-negative disease has historically been defined as those with IHC scores of 0 or 1+. This group represents approximately 60% of HER2-negative metastatic breast cancer patients.³ These patients have limited targeted treatment options after progressing on primary therapy. Prior data has shown that patients with low HER2 expression represent a heterogeneous population and thus, the historic categorization of HER2 status as positive or negative may in fact not adequately characterize the proportion of patients who may derive clinical benefit from HER2-directed therapies. Nevertheless, there have been no data to date that have shown improved outcomes in low HER2 expressers with anti-HER2 therapies.

The current studies add to the rapidly growing body of literature outlining the efficacy of the novel antibody drug conjugate trastuzumab deruxtecan. The implications of the data presented in these 2 studies are immediately practice changing.

In the DESTINY-Breast03 trial, Cortéz and colleagues show that trastuzumab deruxtecan therapy significantly prolongs progression-free survival compared with trastuzumab emtansine in patients with HER2-positive metastatic breast cancer who have progressed on first-line trastuzumab and taxane-based therapy. With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in this trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer. The overall survival in this trial was immature at the time of this analysis, and thus continued follow-up to validate the results noted here are warranted.

The DESTINY-Breast04 trial by Modi et al expands the cohort of patients who benefit from trastuzumab deruxtecan profoundly. This study defines a population of patients with HER2-low metastatic breast cancer who will now be eligible for HER2-directed therapies. These data show that therapy with trastuzumab deruxtecan leads to a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy in patients with metastatic breast cancer with low expression of HER2. This benefit was seen in both the estrogen receptor–positive cohort as well as the entire population, including pre-treated triple-negative disease. Furthermore, this study does not define a threshold of HER2 expression by IHC that predicts benefit with trastuzumab deruxtecan. Patients with an IHC score of 1+ as well as those with a score of 2+/ISH negative both benefit to a similar extent from trastuzumab deruxtecan. Interestingly, in the DAISY trial, antitumor activity was noted with trastuzumab deruxtecan even in those without any detectable HER2 expression on IHC.⁴ Given the inconsistency and potential false negatives of IHC along with heterogeneous HER2 expression, further work is needed to better identify patients with low levels of HER2 expression who may benefit from this novel antibody drug conjugate. Thus, a reliable test to quantitatively assess the level of HER2 expression is needed in order to determine more accurately which patients will benefit from trastuzumab deruxtecan.

Last, trastuzumab deruxtecan has been associated with interstitial lung disease and pneumonitis. Interstitial lung disease and pneumonitis occurred in approximately 10% of patients who received trastuzumab deruxtecan in the DESTINY-Breast03 trial and about 12% of patients in the DESTINY-Breast04 trial. Most of these events were grade 1 and grade 2. Nevertheless, clinicians must be aware of this risk and monitor patients frequently for the development of pneumonitis or interstitial lung disease.

Application for Clinical Practice and System Implementation

The results of the current studies show a longer progression-free survival with trastuzumab deruxtecan in both HER2-low expressing metastatic breast cancer and HER2-positive metastatic breast cancer following taxane and trastuzumab-based therapy. These results are clearly practice changing and represent a new standard of care in these patient populations. It is incumbent upon treating oncologists to work with our pathology colleagues to assess HER2 IHC thoroughly in order to identify all potential patients who may benefit from trastuzumab deruxtecan in the metastatic setting. The continued advancement of anti-HER2 therapy will undoubtedly have a significant impact on patient outcomes going forward.

Practice Points

• With a hazard ratio of 0.28 for disease progression or death, the efficacy of trastuzumab deruxtecan highlighted in the DESTINY-Breast03 trial clearly makes this the standard of care in the second-line setting for patients with metastatic HER2-positive breast cancer.
• In the DESTINY-Breast04 trial, a significant and clinically meaningful improvement in both progression-free survival and overall survival compared with chemotherapy was seen in patients with metastatic breast cancer with low expression of HER2, including both the estrogen receptor–positive cohort as well as the entire population, including those with pre-treated triple-negative disease.

­—Daniel Isaac, DO, MS

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

Midlife women who are of normal weight or are overweight should routinely receive counseling aimed at limiting weight gain and preventing obesity and its associated health risks, a new clinical guideline states.

The recommendation, issued by the Women’s Preventive Services Initiative (WPSI) of the American College of Obstetricians and Gynecologists (ACOG), supports regular lifestyle counseling for women aged 40-60 years with normal or overweight body mass index of 18.5-29.9 kg/m². Counseling could include individualized discussion of healthy eating and physical activity initiated by health professionals involved in preventive care.

Published online in Annals of Internal Medicine, the guideline addresses the prevalence and health burdens of obesity in U.S. women of middle age and seeks to reduce the known harms of obesity with an intervention of minimal anticipated harms. High BMI increases the risk for many chronic conditions including hypertension, dyslipidemia, type 2 diabetes, coronary artery disease, stroke, and all-cause mortality.

The best way to counsel, however, remains unclear. “Although the optimal approach could not be discerned from existing trials, a range of interventions of varying duration, frequency, and intensity showed benefit with potential clinical significance,” wrote the WPSI guideline panel, led by David P. Chelmow, MD, chair of the department of obstetrics and gynecology at Virginia Commonwealth University in Richmond.

The guideline rests on a systematic literature review led by family doctor Amy G. Cantor, MD, MPH, of the Pacific Northwest Evidence-based Practice Center, at Oregon Health & Science University in Portland, suggesting moderate reductions in weight could be achieved by offering advice to this age group.

The federally supported WPSI was launched by ACOG in 2016. The guideline fills a gap in current recommendations in that it targets a specific risk group and specifies individual counseling based on its effectiveness and applicability in primary care settings.

In another benefit of routine counseling, the panel stated, “Normalizing counseling about healthy diet and physical activity by providing it to all midlife women may also mitigate concerns about weight stigma resulting from only counseling women with obesity.”

The panelists noted that during 2017-2018, the prevalence of obesity (BMI ≥ 30.0 kg/m²) was 43.3% among U.S. women aged 40-59 years, while the prevalence of severe obesity (BMI ≥ 40.0 kg/m²) was highest in this age group at 11.5%. “Midlife women gain weight at an average of approximately 1.5 pounds per year, which increases their risk for transitioning from normal or overweight to obese BMI,” the panelists wrote.

The review

Dr. Cantor’s group analyzed seven randomized controlled trials (RCTs) published up to October 2021 from 12 publications involving 51,638 participants. Although the trials were largely small and heterogeneous, they suggested that counseling may result in modest differences in weight change without causing important harms.

Four RCTs showed significant favorable weight changes for counseling over no-counseling control groups, with a mean difference of 0.87 to 2.5 kg, whereas one trial of counseling and two trials of exercise showed no differences. One of two RCTs reported improved quality-of-life measures.

As for harms, while interventions did not increase measures of depression or stress in one trial, self-reported falls (37% vs. 29%, P < .001) and injuries (19% vs. 14%, P = .03) were more frequent with exercise counseling in one trial.

“More research is needed to determine optimal content, frequency, length, and number of sessions required and should include additional patient populations,” Dr. Cantor and associates wrote.

In terms of limitations, the authors acknowledged that trials of behavioral interventions in maintaining or reducing weight in midlife women demonstrate small magnitudes of effect.

Offering a nonparticipant’s perspective on the WPSI guideline for this news organization, JoAnn E. Manson, MD, DrPH, MACP, chief of the division of preventive medicine at Brigham and Women’s Hospital in Boston, said its message is of prime importance for women of middle age and it goes beyond concern about pounds lost or gained.

“Midlife and the transition to menopause are high-risk periods for women in terms of typical changes in body composition that increase the risk of adverse cardiometabolic outcomes,” said Dr. Manson, professor of women’s health at Harvard Medical School, Boston. “Counseling women should be a priority for physicians in clinical practice. And it’s not just whether weight gain is reflected on the scales or not but whether there’s an increase in central abdominal fat, a decrease in lean muscle mass, and an increase in adverse glucose tolerance.”

It is essential for women to be vigilant at this time, she added, and their exercise regimens should include strength and resistance training to preserve lean muscle mass and boost metabolic rate. Dr. Manson’s group has issued several statements stressing how important it is for clinicians to take decisive action on the counseling front and how they can do this in very little time during routine practice.

Also in full support of the guideline is Mary L. Rosser, MD, PhD, assistant professor of women’s health in obstetrics and gynecology at Columbia University Irving Medical Center in New York. “Midlife is a wonderful opportunity to encourage patients to assess their overall health status and make changes to impact their future health. Women in middle age tend to experience weight gain due to a variety of factors including aging and lifestyle,” said Dr. Rosser, who was not involved in the writing of the review or guideline.

While aging and genetics cannot be altered, behaviors can, and in her view, favorable behaviors would also include stress reduction and adequate sleep.

“The importance of reducing obesity with early intervention and prevention must focus on all women,” Dr. Rosser said. “We must narrow the inequities gap in care especially for high-risk minority groups and underserved populations. This will reduce disease and death and provide women the gift of active living and feeling better.”

The WPSI authors have made available a summary of the review and guideline for patients.

The systematic review and clinical guideline were funded by the federal Health Resources and Services Administration through ACOG. The authors of the guideline and the review authors disclosed no relevant financial conflicts of interest. Dr. Manson and Dr. Rosser disclosed no relevant competing interests with regard to their comments.

New results with quadruple drug therapy in the frontline treatment of multiple myeloma (MM) are prompting experts to speculate that stem cell transplantation may soon be able to take a back seat in the treatment of newly diagnosed disease.

“It is not a big leap of faith to imagine that, in the near future, with the availability of quadruplets and T-cell therapies, the role of high-dose melphalan and autologous stem cell transplant will be diminished,” said Dickran Kazandjian, MD, and Ola Landgren, MD, PhD, of the myeloma division, Sylvester Comprehensive Cancer Center, University of Miami.

They commented in a editorial in JAMA Oncology, prompted by a paper describing new results with a novel quadruple combination of therapies. These treatments included the monoclonal antibody elotuzumab (Empliciti) added onto the established backbone of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (known as KRd).

“Regardless of what the future holds for elotuzumab-based combinations, it is clear that the new treatment paradigm of newly diagnosed MM will incorporate antibody-based quadruplet regimens,” the editorialists commented.

“Novel immunotherapies are here to stay,” they added, “as they are already transforming the lives of patients with multiple MM and bringing a bright horizon to the treatment landscape.”
 

Study details

The trial of the novel quadruplet regimen was a multicenter, single-arm, phase 2 study that involved 46 patients with newly diagnosed multiple myeloma, explain first author Benjamin A. Derman, MD, of the University of Chicago Medical Center, and colleagues.

These patients had a median age of 62; more than two-thirds were male (72%) and White (70%). About half (48%) had high-risk cytogenetic abnormalities.

All patients were treated with 12 cycles of the quadruple therapy Elo-KRd regimen. They underwent bone marrow assessment of measurable residual disease (MRD; with 10-5 sensitivity) after cycle 8 and cycle 12.

“An MRD-adapted treatment approach is rational because it may identify which patients can be administered shorter courses of intensive therapy without compromising efficacy,” the authors explained.

Patients who had MRD negativity at both time points did not receive further Elo-KRd, while patients who converted from MRD positivity to negativity in between cycles 8 and 12 received 6 additional cycles of Elo-KRd. Those who remained MRD positive or converted to positivity after 12 cycles received an additional 12 cycles of Elo-KRd.

Following Elo-KRd treatment, all patients transitioned to triple therapy with Elo-Rd (with no carfilzomib), for indefinite maintenance therapy or until disease progression.

For the primary endpoint, the rate of stringent complete response and/or MRD-negativity after cycle 8 was 58% (26 of 45), meeting the predefined definition of efficacy. 

Importantly, 26% of patients converted from MRD positivity after cycle 8 to negativity at a later time point, while 50% of patients reached 1-year sustained MRD negativity.

Overall, the estimated 3-year, progression-free survival was 72%, and the rate was 92% for patients with MRD-negativity at cycle 8. The overall survival rate was 78%.

The most common grade 3 or 4 adverse events were lung and nonpulmonary infections (13% and 11%, respectively), and one patient had a grade 5 MI. Three patients discontinued the treatment because of intolerance.

“An MRD-adapted design using elotuzumab and weekly KRd without autologous stem cell transplantation showed a high rate of stringent complete response (sCR) and/or MRD-negativity and durable responses,” the authors wrote.

“This approach provides support for further evaluation of MRD-guided de-escalation of therapy to decrease treatment exposure while sustaining deep responses.”

To better assess the difference of the therapy versus treatment including stem cell transplantation, a phase 3, randomized trial is currently underway to compare the Elo-KRd regimen against KRd with autologous stem cell transplant in newly diagnosed MM.

“If Elo-KRd proves superior, a randomized comparison of Elo versus anti-CD38 mAb-based quadruplets would help determine the optimal combination of therapies in the frontline setting,” the authors noted.
 

Randomized trial anticipated to clarify benefit

In their editorial, Dr. Kazandjian and Dr. Landgren agreed with the authors that the role of elotuzumab needs to be better clarified in a randomized trial setting.

Elotuzumab received FDA approval in 2015 based on results from the ELOQUENT-2 study, which showed improved progression-free survival and overall survival with the addition of elotuzumab to lenalidomide and dexamethasone in patients with multiple myeloma who have previously received one to three other therapies.

However, the editorialists pointed out that recently published results from the randomized ELOQUENT-1 trial of lenalidomide and dexamethasone with and without elotuzumab showed the addition of elotuzumab was not associated with a statistically significant difference in progression-free survival.

The editorialists also pointed out that, in the setting of newly diagnosed multiple myeloma, another recent, similarly designed study found that the backbone regimen of carfilzomib, lenalidomide, and dexamethasone – on its own – was also associated with a favorable MRD-negative rate of 62%.

In addition, several studies involving novel quadruple treatments with the monoclonal antibody daratumumab (Darzalex) instead of elotuzumab, have also shown benefit in newly diagnosed multiple myeloma, resulting in high rates of MRD negativity.

Collectively, the findings bode well for the quadruple regimens in the treatment of MM, the editorialists emphasized.

“Importantly, with the rate of deep remissions observed with antibody-based quadruplet therapies, one may question the role of using early high-dose melphalan and autologous stem cell transplant in every patient, especially in those who have achieved MRD negativity with the quadruplet alone,” they added.

The study was sponsored in part by Amgen, Bristol-Myers Squibb, and the Multiple Myeloma Research Consortium. Dr. Derman reported advisory board fees from Sanofi, Janssen, and COTA Healthcare; honoraria from PleXus Communications and MJH Life Sciences. Dr. Kazandjian declares receiving advisory board or consulting fees from Bristol-Myers Squibb, Sanofi, and Arcellx outside the submitted work. Dr. Landgren has received grant support from numerous organizations and pharmaceutical companies. Dr. Landgren has also received honoraria for scientific talks/participated in advisory boards for Adaptive Biotech, Amgen, Binding Site, Bristol-Myers Squibb, Celgene, Cellectis, Glenmark, Janssen, Juno, and Pfizer, and served on independent data monitoring committees for international randomized trials by Takeda, Merck, Janssen, and Theradex.

A version of this article first appeared on Medscape.com.

New results with quadruple drug therapy in the frontline treatment of multiple myeloma (MM) are prompting experts to speculate that stem cell transplantation may soon be able to take a back seat in the treatment of newly diagnosed disease.

“It is not a big leap of faith to imagine that, in the near future, with the availability of quadruplets and T-cell therapies, the role of high-dose melphalan and autologous stem cell transplant will be diminished,” said Dickran Kazandjian, MD, and Ola Landgren, MD, PhD, of the myeloma division, Sylvester Comprehensive Cancer Center, University of Miami.

They commented in a editorial in JAMA Oncology, prompted by a paper describing new results with a novel quadruple combination of therapies. These treatments included the monoclonal antibody elotuzumab (Empliciti) added onto the established backbone of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (known as KRd).

“Regardless of what the future holds for elotuzumab-based combinations, it is clear that the new treatment paradigm of newly diagnosed MM will incorporate antibody-based quadruplet regimens,” the editorialists commented.

“Novel immunotherapies are here to stay,” they added, “as they are already transforming the lives of patients with multiple MM and bringing a bright horizon to the treatment landscape.”
 

Study details

The trial of the novel quadruplet regimen was a multicenter, single-arm, phase 2 study that involved 46 patients with newly diagnosed multiple myeloma, explain first author Benjamin A. Derman, MD, of the University of Chicago Medical Center, and colleagues.

These patients had a median age of 62; more than two-thirds were male (72%) and White (70%). About half (48%) had high-risk cytogenetic abnormalities.

All patients were treated with 12 cycles of the quadruple therapy Elo-KRd regimen. They underwent bone marrow assessment of measurable residual disease (MRD; with 10-5 sensitivity) after cycle 8 and cycle 12.

“An MRD-adapted treatment approach is rational because it may identify which patients can be administered shorter courses of intensive therapy without compromising efficacy,” the authors explained.

Patients who had MRD negativity at both time points did not receive further Elo-KRd, while patients who converted from MRD positivity to negativity in between cycles 8 and 12 received 6 additional cycles of Elo-KRd. Those who remained MRD positive or converted to positivity after 12 cycles received an additional 12 cycles of Elo-KRd.

Following Elo-KRd treatment, all patients transitioned to triple therapy with Elo-Rd (with no carfilzomib), for indefinite maintenance therapy or until disease progression.

For the primary endpoint, the rate of stringent complete response and/or MRD-negativity after cycle 8 was 58% (26 of 45), meeting the predefined definition of efficacy. 

Importantly, 26% of patients converted from MRD positivity after cycle 8 to negativity at a later time point, while 50% of patients reached 1-year sustained MRD negativity.

Overall, the estimated 3-year, progression-free survival was 72%, and the rate was 92% for patients with MRD-negativity at cycle 8. The overall survival rate was 78%.

The most common grade 3 or 4 adverse events were lung and nonpulmonary infections (13% and 11%, respectively), and one patient had a grade 5 MI. Three patients discontinued the treatment because of intolerance.

“An MRD-adapted design using elotuzumab and weekly KRd without autologous stem cell transplantation showed a high rate of stringent complete response (sCR) and/or MRD-negativity and durable responses,” the authors wrote.

“This approach provides support for further evaluation of MRD-guided de-escalation of therapy to decrease treatment exposure while sustaining deep responses.”

To better assess the difference of the therapy versus treatment including stem cell transplantation, a phase 3, randomized trial is currently underway to compare the Elo-KRd regimen against KRd with autologous stem cell transplant in newly diagnosed MM.

“If Elo-KRd proves superior, a randomized comparison of Elo versus anti-CD38 mAb-based quadruplets would help determine the optimal combination of therapies in the frontline setting,” the authors noted.
 

Randomized trial anticipated to clarify benefit

In their editorial, Dr. Kazandjian and Dr. Landgren agreed with the authors that the role of elotuzumab needs to be better clarified in a randomized trial setting.

Elotuzumab received FDA approval in 2015 based on results from the ELOQUENT-2 study, which showed improved progression-free survival and overall survival with the addition of elotuzumab to lenalidomide and dexamethasone in patients with multiple myeloma who have previously received one to three other therapies.

However, the editorialists pointed out that recently published results from the randomized ELOQUENT-1 trial of lenalidomide and dexamethasone with and without elotuzumab showed the addition of elotuzumab was not associated with a statistically significant difference in progression-free survival.

The editorialists also pointed out that, in the setting of newly diagnosed multiple myeloma, another recent, similarly designed study found that the backbone regimen of carfilzomib, lenalidomide, and dexamethasone – on its own – was also associated with a favorable MRD-negative rate of 62%.

In addition, several studies involving novel quadruple treatments with the monoclonal antibody daratumumab (Darzalex) instead of elotuzumab, have also shown benefit in newly diagnosed multiple myeloma, resulting in high rates of MRD negativity.

Collectively, the findings bode well for the quadruple regimens in the treatment of MM, the editorialists emphasized.

“Importantly, with the rate of deep remissions observed with antibody-based quadruplet therapies, one may question the role of using early high-dose melphalan and autologous stem cell transplant in every patient, especially in those who have achieved MRD negativity with the quadruplet alone,” they added.

The study was sponsored in part by Amgen, Bristol-Myers Squibb, and the Multiple Myeloma Research Consortium. Dr. Derman reported advisory board fees from Sanofi, Janssen, and COTA Healthcare; honoraria from PleXus Communications and MJH Life Sciences. Dr. Kazandjian declares receiving advisory board or consulting fees from Bristol-Myers Squibb, Sanofi, and Arcellx outside the submitted work. Dr. Landgren has received grant support from numerous organizations and pharmaceutical companies. Dr. Landgren has also received honoraria for scientific talks/participated in advisory boards for Adaptive Biotech, Amgen, Binding Site, Bristol-Myers Squibb, Celgene, Cellectis, Glenmark, Janssen, Juno, and Pfizer, and served on independent data monitoring committees for international randomized trials by Takeda, Merck, Janssen, and Theradex.

A version of this article first appeared on Medscape.com.

New results with quadruple drug therapy in the frontline treatment of multiple myeloma (MM) are prompting experts to speculate that stem cell transplantation may soon be able to take a back seat in the treatment of newly diagnosed disease.

“It is not a big leap of faith to imagine that, in the near future, with the availability of quadruplets and T-cell therapies, the role of high-dose melphalan and autologous stem cell transplant will be diminished,” said Dickran Kazandjian, MD, and Ola Landgren, MD, PhD, of the myeloma division, Sylvester Comprehensive Cancer Center, University of Miami.

They commented in a editorial in JAMA Oncology, prompted by a paper describing new results with a novel quadruple combination of therapies. These treatments included the monoclonal antibody elotuzumab (Empliciti) added onto the established backbone of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (known as KRd).

“Regardless of what the future holds for elotuzumab-based combinations, it is clear that the new treatment paradigm of newly diagnosed MM will incorporate antibody-based quadruplet regimens,” the editorialists commented.

“Novel immunotherapies are here to stay,” they added, “as they are already transforming the lives of patients with multiple MM and bringing a bright horizon to the treatment landscape.”
 

Study details

The trial of the novel quadruplet regimen was a multicenter, single-arm, phase 2 study that involved 46 patients with newly diagnosed multiple myeloma, explain first author Benjamin A. Derman, MD, of the University of Chicago Medical Center, and colleagues.

These patients had a median age of 62; more than two-thirds were male (72%) and White (70%). About half (48%) had high-risk cytogenetic abnormalities.

All patients were treated with 12 cycles of the quadruple therapy Elo-KRd regimen. They underwent bone marrow assessment of measurable residual disease (MRD; with 10-5 sensitivity) after cycle 8 and cycle 12.

“An MRD-adapted treatment approach is rational because it may identify which patients can be administered shorter courses of intensive therapy without compromising efficacy,” the authors explained.

Patients who had MRD negativity at both time points did not receive further Elo-KRd, while patients who converted from MRD positivity to negativity in between cycles 8 and 12 received 6 additional cycles of Elo-KRd. Those who remained MRD positive or converted to positivity after 12 cycles received an additional 12 cycles of Elo-KRd.

Following Elo-KRd treatment, all patients transitioned to triple therapy with Elo-Rd (with no carfilzomib), for indefinite maintenance therapy or until disease progression.

For the primary endpoint, the rate of stringent complete response and/or MRD-negativity after cycle 8 was 58% (26 of 45), meeting the predefined definition of efficacy. 

Importantly, 26% of patients converted from MRD positivity after cycle 8 to negativity at a later time point, while 50% of patients reached 1-year sustained MRD negativity.

Overall, the estimated 3-year, progression-free survival was 72%, and the rate was 92% for patients with MRD-negativity at cycle 8. The overall survival rate was 78%.

The most common grade 3 or 4 adverse events were lung and nonpulmonary infections (13% and 11%, respectively), and one patient had a grade 5 MI. Three patients discontinued the treatment because of intolerance.

“An MRD-adapted design using elotuzumab and weekly KRd without autologous stem cell transplantation showed a high rate of stringent complete response (sCR) and/or MRD-negativity and durable responses,” the authors wrote.

“This approach provides support for further evaluation of MRD-guided de-escalation of therapy to decrease treatment exposure while sustaining deep responses.”

To better assess the difference of the therapy versus treatment including stem cell transplantation, a phase 3, randomized trial is currently underway to compare the Elo-KRd regimen against KRd with autologous stem cell transplant in newly diagnosed MM.

“If Elo-KRd proves superior, a randomized comparison of Elo versus anti-CD38 mAb-based quadruplets would help determine the optimal combination of therapies in the frontline setting,” the authors noted.
 

Randomized trial anticipated to clarify benefit

In their editorial, Dr. Kazandjian and Dr. Landgren agreed with the authors that the role of elotuzumab needs to be better clarified in a randomized trial setting.

Elotuzumab received FDA approval in 2015 based on results from the ELOQUENT-2 study, which showed improved progression-free survival and overall survival with the addition of elotuzumab to lenalidomide and dexamethasone in patients with multiple myeloma who have previously received one to three other therapies.

However, the editorialists pointed out that recently published results from the randomized ELOQUENT-1 trial of lenalidomide and dexamethasone with and without elotuzumab showed the addition of elotuzumab was not associated with a statistically significant difference in progression-free survival.

The editorialists also pointed out that, in the setting of newly diagnosed multiple myeloma, another recent, similarly designed study found that the backbone regimen of carfilzomib, lenalidomide, and dexamethasone – on its own – was also associated with a favorable MRD-negative rate of 62%.

In addition, several studies involving novel quadruple treatments with the monoclonal antibody daratumumab (Darzalex) instead of elotuzumab, have also shown benefit in newly diagnosed multiple myeloma, resulting in high rates of MRD negativity.

Collectively, the findings bode well for the quadruple regimens in the treatment of MM, the editorialists emphasized.

“Importantly, with the rate of deep remissions observed with antibody-based quadruplet therapies, one may question the role of using early high-dose melphalan and autologous stem cell transplant in every patient, especially in those who have achieved MRD negativity with the quadruplet alone,” they added.

The study was sponsored in part by Amgen, Bristol-Myers Squibb, and the Multiple Myeloma Research Consortium. Dr. Derman reported advisory board fees from Sanofi, Janssen, and COTA Healthcare; honoraria from PleXus Communications and MJH Life Sciences. Dr. Kazandjian declares receiving advisory board or consulting fees from Bristol-Myers Squibb, Sanofi, and Arcellx outside the submitted work. Dr. Landgren has received grant support from numerous organizations and pharmaceutical companies. Dr. Landgren has also received honoraria for scientific talks/participated in advisory boards for Adaptive Biotech, Amgen, Binding Site, Bristol-Myers Squibb, Celgene, Cellectis, Glenmark, Janssen, Juno, and Pfizer, and served on independent data monitoring committees for international randomized trials by Takeda, Merck, Janssen, and Theradex.

A version of this article first appeared on Medscape.com.

SAN DIEGO – For the first time, the Alzheimer’s Association has released recommendations for the use of blood-based biomarkers in clinical trials and certain clinical situations. The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.

The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.

During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.

The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
 

Guidance for clinical trials and memory clinics

The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.

The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.

However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.

The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.

Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.

In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.
 

More work to be done

Dr. Hansson noted that 50%-70% of patients with Alzheimer’s disease are misdiagnosed in primary care, showing a clear need for biomarkers that could improve diagnosis. However, he stressed that blood-based biomarkers are not yet ready for use in that setting.

Still, they could eventually become a boon. “The majority of patients now do not get any biomarker support to diagnosis. They do not have access to amyloid PET or [CSF] biomarkers, but when the blood-based biomarkers are good enough, that means that biomarker support for an Alzheimer’s diagnosis [will be] available to many patients … across the globe,” said Dr. van der Flier.

There are numerous research efforts underway to validate blood-based biomarkers in more diverse groups of patients. That’s because the retrospective studies typically used to identify and validate biomarkers tend to recruit carefully selected patients, with clearly defined cases and good CSF characterization, according to Charlotte Teunissen, PhD, who is also a coauthor of the guidelines and professor of neuropsychiatry at Amsterdam University Medical Center. “Now we want to go one step further to go real-life practice, and there are several initiatives,” she said.

Dr. Hansson, Dr. Tenuissen, and Dr. van der Flier have no relevant financial disclosures.

SAN DIEGO – For the first time, the Alzheimer’s Association has released recommendations for the use of blood-based biomarkers in clinical trials and certain clinical situations. The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.

The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.

During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.

The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
 

Guidance for clinical trials and memory clinics

The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.

The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.

However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.

The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.

Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.

In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.
 

More work to be done

Dr. Hansson noted that 50%-70% of patients with Alzheimer’s disease are misdiagnosed in primary care, showing a clear need for biomarkers that could improve diagnosis. However, he stressed that blood-based biomarkers are not yet ready for use in that setting.

Still, they could eventually become a boon. “The majority of patients now do not get any biomarker support to diagnosis. They do not have access to amyloid PET or [CSF] biomarkers, but when the blood-based biomarkers are good enough, that means that biomarker support for an Alzheimer’s diagnosis [will be] available to many patients … across the globe,” said Dr. van der Flier.

There are numerous research efforts underway to validate blood-based biomarkers in more diverse groups of patients. That’s because the retrospective studies typically used to identify and validate biomarkers tend to recruit carefully selected patients, with clearly defined cases and good CSF characterization, according to Charlotte Teunissen, PhD, who is also a coauthor of the guidelines and professor of neuropsychiatry at Amsterdam University Medical Center. “Now we want to go one step further to go real-life practice, and there are several initiatives,” she said.

Dr. Hansson, Dr. Tenuissen, and Dr. van der Flier have no relevant financial disclosures.

SAN DIEGO – For the first time, the Alzheimer’s Association has released recommendations for the use of blood-based biomarkers in clinical trials and certain clinical situations. The organization has previously published recommendations for use of amyloid positron emission tomography (PET) and cerebrospinal fluid (CSF) biomarkers for Alzheimer’s disease.

The recommendations were the subject of a presentation at the 2022 Alzheimer’s Association International Conference and were published online in Alzheimer’s & Dementia.

During his presentation, Oskar Hansson, MD, PhD, stressed that the document describes recommendations, not criteria, for use of blood-based biomarkers. He suggested that the recommendations will need to be updated within 9-12 months, and that criteria for blood-based biomarkers use could come within 2 years.

The new recommendations reflect the recent acceleration of progress in the field, according to Wiesje M. van der Flier, PhD, who moderated the session. “It’s just growing so quickly. I think within 5 years the whole field will have transformed. By starting to use them in specialized memory clinics first, but then also local memory clinics, and then finally, I think that they may also transform primary care,” said Dr. van der Flier, who is a professor of neurology at Amsterdam University Medical Center.
 

Guidance for clinical trials and memory clinics

The guidelines were created in part because blood-based biomarkers for Alzheimer’s disease have become increasingly available, and there has been a call from the community for guidance, according to Dr. Hansson. There is also a hazard that widespread adoption could interfere with the field itself, especially if physicians don’t understand how to interpret the results. That’s a particularly acute problem since Alzheimer’s disease pathology can precede symptoms. “It’s important to have some guidance about regulating their use so we don’t get the problem that they are misused and get a bad reputation,” said Dr. Hansson in an interview.

The current recommendations are for use in clinical trials to identify patients likely to have Alzheimer’s disease, as well as in memory clinics, though “we’re still a bit cautious. We still need to confirm it with other biomarkers. The reason for that is we still don’t know how these will perform in the clinical reality. So it’s a bit trying it out. You can start using these blood biomarkers to some degree,” said Dr. Hansson.

However, he offered the caveat that plasma-based biomarkers should only be used while confirming that the blood-based biomarkers agree with CSF tests, ideally more than 90% of the time. “If suddenly only 60% of the plasma biomarkers agree with CSF, you have a problem and you need to stop,” said Dr. Hansson.

The authors recommend that blood-based biomarkers be used in clinical trials to help select patients and identify healthy controls. Dr. Hansson said that there is not enough evidence that blood-based biomarkers have sufficient positive predictive value to be used as the sole criteria for clinical trial admission. However, they could also be used to inform decision-making in adaptive clinical trials.

Specifically, plasma Abeta42/Abeta40 and P-tau assays using established thresholds can be used in clinical studies first-screening step for clinical trials, though they should be confirmed by PET or CSF in those with abnormal blood biomarker levels. The biomarkers could also be used in non–Alzheimer’s disease clinical trials to exclude patients with probable Alzheimer’s disease copathology.

In memory clinics, the authors recommend that BBMs be used only in patients who are symptomatic and, when possible, should be confirmed by PET or CSF.
 

More work to be done

Dr. Hansson noted that 50%-70% of patients with Alzheimer’s disease are misdiagnosed in primary care, showing a clear need for biomarkers that could improve diagnosis. However, he stressed that blood-based biomarkers are not yet ready for use in that setting.

Still, they could eventually become a boon. “The majority of patients now do not get any biomarker support to diagnosis. They do not have access to amyloid PET or [CSF] biomarkers, but when the blood-based biomarkers are good enough, that means that biomarker support for an Alzheimer’s diagnosis [will be] available to many patients … across the globe,” said Dr. van der Flier.

There are numerous research efforts underway to validate blood-based biomarkers in more diverse groups of patients. That’s because the retrospective studies typically used to identify and validate biomarkers tend to recruit carefully selected patients, with clearly defined cases and good CSF characterization, according to Charlotte Teunissen, PhD, who is also a coauthor of the guidelines and professor of neuropsychiatry at Amsterdam University Medical Center. “Now we want to go one step further to go real-life practice, and there are several initiatives,” she said.

Dr. Hansson, Dr. Tenuissen, and Dr. van der Flier have no relevant financial disclosures.

Edgewell Personal Care Co., the maker of Banana Boat sunscreen, is recalling a scalp spray because it contains trace levels of benzene, a chemical that can cause cancer at high levels.

The company announced a voluntary recall for three batches of the Banana Boat Hair & Scalp Spray SPF 30, which came in 6-ounce bottles and was sold across the U.S. through various retailers and online, according to a recall alert by the Food and Drug Administration.

The three batches have a UPC label of 0-79656-04041-8 and fall under the lot codes 20016AF, 20084BF, and 21139AF, with the expiration dates of December 2022, February 2023, and April 2024, respectively.

“An internal review found that some samples of the product contained trace levels of benzene. While benzene is not an ingredient in any Banana Boat products, the review showed the unexpected levels of benzene came from the propellant that sprays the product out of the can,” according to the recall notice.

“Importantly, no other batches of Hair & Scalp (either before or after these batch codes) and no other Banana Boat products are in the scope of this recall and may continue to be used by consumers safely and as intended,” the company wrote.

Benzene is classified as a human carcinogen, the FDA wrote. Exposure to benzene can occur through the nose, mouth, and skin, and it can result in serious conditions such as leukemia, bone marrow cancer, and blood disorders.

“Benzene is ubiquitous in the environment. Humans around the world have daily exposures to it indoors and outdoors from multiple sources,” the company said. “Daily exposure to benzene in the recalled products would not be expected to cause adverse health consequences according to an independent health assessment using established exposure modeling guidelines.”

Edgewell said it hasn’t received any reports of bad events related to the recall. The company has told retailers to remove the affected batches from shelves.

Banana Boat will reimburse consumers who purchased a product with one of the affected lot codes, which are on the bottom of the can. In the meantime, consumers should stop using the affected product right away and discard it.

The recall comes a little over a year after Johnson & Johnson recalled five sunscreens due to low levels of benzene, according to The Associated Press. That recall included Aveeno and Neutrogena products in spray cans.

Consumers with questions about the recall can contact Edgewell Personal Care at 888-686-3988 Monday through Friday, 9 a.m. to 6 p.m. ET. People can also read more at the Banana Boat FAQ page or file for a refund directly on the Banana Boat Recall page.

A version of this article first appeared on WebMD.com.

Edgewell Personal Care Co., the maker of Banana Boat sunscreen, is recalling a scalp spray because it contains trace levels of benzene, a chemical that can cause cancer at high levels.

The company announced a voluntary recall for three batches of the Banana Boat Hair & Scalp Spray SPF 30, which came in 6-ounce bottles and was sold across the U.S. through various retailers and online, according to a recall alert by the Food and Drug Administration.

The three batches have a UPC label of 0-79656-04041-8 and fall under the lot codes 20016AF, 20084BF, and 21139AF, with the expiration dates of December 2022, February 2023, and April 2024, respectively.

“An internal review found that some samples of the product contained trace levels of benzene. While benzene is not an ingredient in any Banana Boat products, the review showed the unexpected levels of benzene came from the propellant that sprays the product out of the can,” according to the recall notice.

“Importantly, no other batches of Hair & Scalp (either before or after these batch codes) and no other Banana Boat products are in the scope of this recall and may continue to be used by consumers safely and as intended,” the company wrote.

Benzene is classified as a human carcinogen, the FDA wrote. Exposure to benzene can occur through the nose, mouth, and skin, and it can result in serious conditions such as leukemia, bone marrow cancer, and blood disorders.

“Benzene is ubiquitous in the environment. Humans around the world have daily exposures to it indoors and outdoors from multiple sources,” the company said. “Daily exposure to benzene in the recalled products would not be expected to cause adverse health consequences according to an independent health assessment using established exposure modeling guidelines.”

Edgewell said it hasn’t received any reports of bad events related to the recall. The company has told retailers to remove the affected batches from shelves.

Banana Boat will reimburse consumers who purchased a product with one of the affected lot codes, which are on the bottom of the can. In the meantime, consumers should stop using the affected product right away and discard it.

The recall comes a little over a year after Johnson & Johnson recalled five sunscreens due to low levels of benzene, according to The Associated Press. That recall included Aveeno and Neutrogena products in spray cans.

Consumers with questions about the recall can contact Edgewell Personal Care at 888-686-3988 Monday through Friday, 9 a.m. to 6 p.m. ET. People can also read more at the Banana Boat FAQ page or file for a refund directly on the Banana Boat Recall page.

A version of this article first appeared on WebMD.com.

Edgewell Personal Care Co., the maker of Banana Boat sunscreen, is recalling a scalp spray because it contains trace levels of benzene, a chemical that can cause cancer at high levels.

The company announced a voluntary recall for three batches of the Banana Boat Hair & Scalp Spray SPF 30, which came in 6-ounce bottles and was sold across the U.S. through various retailers and online, according to a recall alert by the Food and Drug Administration.

The three batches have a UPC label of 0-79656-04041-8 and fall under the lot codes 20016AF, 20084BF, and 21139AF, with the expiration dates of December 2022, February 2023, and April 2024, respectively.

“An internal review found that some samples of the product contained trace levels of benzene. While benzene is not an ingredient in any Banana Boat products, the review showed the unexpected levels of benzene came from the propellant that sprays the product out of the can,” according to the recall notice.

“Importantly, no other batches of Hair & Scalp (either before or after these batch codes) and no other Banana Boat products are in the scope of this recall and may continue to be used by consumers safely and as intended,” the company wrote.

Benzene is classified as a human carcinogen, the FDA wrote. Exposure to benzene can occur through the nose, mouth, and skin, and it can result in serious conditions such as leukemia, bone marrow cancer, and blood disorders.

“Benzene is ubiquitous in the environment. Humans around the world have daily exposures to it indoors and outdoors from multiple sources,” the company said. “Daily exposure to benzene in the recalled products would not be expected to cause adverse health consequences according to an independent health assessment using established exposure modeling guidelines.”

Edgewell said it hasn’t received any reports of bad events related to the recall. The company has told retailers to remove the affected batches from shelves.

Banana Boat will reimburse consumers who purchased a product with one of the affected lot codes, which are on the bottom of the can. In the meantime, consumers should stop using the affected product right away and discard it.

The recall comes a little over a year after Johnson & Johnson recalled five sunscreens due to low levels of benzene, according to The Associated Press. That recall included Aveeno and Neutrogena products in spray cans.

Consumers with questions about the recall can contact Edgewell Personal Care at 888-686-3988 Monday through Friday, 9 a.m. to 6 p.m. ET. People can also read more at the Banana Boat FAQ page or file for a refund directly on the Banana Boat Recall page.

A version of this article first appeared on WebMD.com.

“The Best of DDW” elicits in the minds of most readers a compilation of the most important clinical and scientific content presented at DDW.

But I am not referring to that.

The “Best of DDW 2022” was the American Gastroenterological Association Presidential Plenary Session thanks to the humanity and vision of outgoing AGA President John Inadomi, MD.1 I sat in the audience, misty eyed, as each presenter addressed issues that strike deep into our humanity – the social determinants of health that have festered for far too long, leading to intolerable differences in health outcomes based on accidents of birth, and amplified by racism.

As the table on stage slowly filled in, an amazing picture took shape. A majority of the speakers were Black gastroenterologists and hepatologists, and among them many were young women. As I watched the video of a group of young Black gastroenterologists and hepatologists reaching out to the community, I asked myself “Has anything like this ever happened at a major national medical association meeting in the United States? Ever?” And then it occurred to me: “And just imagine, this exactly 2 days before the 2-year anniversary of the death of George Floyd.”

The plenary session happened on May 23, and I was conscious about the dates because I will never forget that George Floyd was killed on May 25, 2020 – my 55th birthday. The juxtaposition of his death and my birthday 2 years ago shook me profoundly, prompting me to write down my reflections and my hope that, in the national reactions that followed, we were seeing the beginning of true change.2 Two years later, despite our national divisions and serious challenges, I have reasons for hope.

On May 24, I ran into a colleague who was a Black woman. I have stopped being afraid to bring up previously untouchable subjects. I asked her what she thought about the remarkable AGA Plenary. She said she was glad that she is here to see it – that her parents never got the chance.

I admitted to her that I often ask myself what more I could and should be doing. I’m trying to do what I can in recruitment, education, in my personal life. What more? She said that one thing we really need is for people who look like me to amplify the message.

So here it is: Readers, listen to the plenary talks if you were not there. At minimum, behold the following line-up of speakers and topics. Feel the history.

This was the Best of DDW 2022:

• Julius Friedenwald Recognition of Timothy Wang. – John Inadomi.
• Presidential Address: Don’t Talk: Act. The relevance of DEI to gastroenterologists and hepatologists and the imperative for action. – John Inadomi.
• AGA Equity Project: Accomplishments and what lies ahead. – Byron L. Cryer, Sandra M. Quezada.
• The genesis and goals of the Association of Black Gastroenterologists and Hepatologists. – Sophie M. Balzora.
• Increasing racial and ethnic diversity in clinical trials: What we need to do. – Monica Webb Hooper.
• Reducing disparities in colorectal cancer. – Rachel Blankson Issaka.
• Reducing disparities in liver disease. – Lauren Nephew.
• Reducing disparities in IBD. – Fernando Velayos.

Uri Ladabaum, MD, MS, is with the division of gastroenterology and hepatology in the department of medicine at Stanford (Calif.) University. He reports serving on the advisory board for UniversalDx and Lean Medical and as a consultant for Medtronic, Clinical Genomics, Guardant Health, and Freenome. Dr. Ladabaum made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

References

1. Inadomi JM. Gastroenterology. 2022 Jun;162(7):1855-7.

2. Ladabaum U. Ann Intern Med. 2020 Dec 1;173(11):938-9.

“The Best of DDW” elicits in the minds of most readers a compilation of the most important clinical and scientific content presented at DDW.

But I am not referring to that.

The “Best of DDW 2022” was the American Gastroenterological Association Presidential Plenary Session thanks to the humanity and vision of outgoing AGA President John Inadomi, MD.1 I sat in the audience, misty eyed, as each presenter addressed issues that strike deep into our humanity – the social determinants of health that have festered for far too long, leading to intolerable differences in health outcomes based on accidents of birth, and amplified by racism.

As the table on stage slowly filled in, an amazing picture took shape. A majority of the speakers were Black gastroenterologists and hepatologists, and among them many were young women. As I watched the video of a group of young Black gastroenterologists and hepatologists reaching out to the community, I asked myself “Has anything like this ever happened at a major national medical association meeting in the United States? Ever?” And then it occurred to me: “And just imagine, this exactly 2 days before the 2-year anniversary of the death of George Floyd.”

The plenary session happened on May 23, and I was conscious about the dates because I will never forget that George Floyd was killed on May 25, 2020 – my 55th birthday. The juxtaposition of his death and my birthday 2 years ago shook me profoundly, prompting me to write down my reflections and my hope that, in the national reactions that followed, we were seeing the beginning of true change.2 Two years later, despite our national divisions and serious challenges, I have reasons for hope.

On May 24, I ran into a colleague who was a Black woman. I have stopped being afraid to bring up previously untouchable subjects. I asked her what she thought about the remarkable AGA Plenary. She said she was glad that she is here to see it – that her parents never got the chance.

I admitted to her that I often ask myself what more I could and should be doing. I’m trying to do what I can in recruitment, education, in my personal life. What more? She said that one thing we really need is for people who look like me to amplify the message.

So here it is: Readers, listen to the plenary talks if you were not there. At minimum, behold the following line-up of speakers and topics. Feel the history.

This was the Best of DDW 2022:

• Julius Friedenwald Recognition of Timothy Wang. – John Inadomi.
• Presidential Address: Don’t Talk: Act. The relevance of DEI to gastroenterologists and hepatologists and the imperative for action. – John Inadomi.
• AGA Equity Project: Accomplishments and what lies ahead. – Byron L. Cryer, Sandra M. Quezada.
• The genesis and goals of the Association of Black Gastroenterologists and Hepatologists. – Sophie M. Balzora.
• Increasing racial and ethnic diversity in clinical trials: What we need to do. – Monica Webb Hooper.
• Reducing disparities in colorectal cancer. – Rachel Blankson Issaka.
• Reducing disparities in liver disease. – Lauren Nephew.
• Reducing disparities in IBD. – Fernando Velayos.

Uri Ladabaum, MD, MS, is with the division of gastroenterology and hepatology in the department of medicine at Stanford (Calif.) University. He reports serving on the advisory board for UniversalDx and Lean Medical and as a consultant for Medtronic, Clinical Genomics, Guardant Health, and Freenome. Dr. Ladabaum made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

References

1. Inadomi JM. Gastroenterology. 2022 Jun;162(7):1855-7.

2. Ladabaum U. Ann Intern Med. 2020 Dec 1;173(11):938-9.

“The Best of DDW” elicits in the minds of most readers a compilation of the most important clinical and scientific content presented at DDW.

But I am not referring to that.

The “Best of DDW 2022” was the American Gastroenterological Association Presidential Plenary Session thanks to the humanity and vision of outgoing AGA President John Inadomi, MD.1 I sat in the audience, misty eyed, as each presenter addressed issues that strike deep into our humanity – the social determinants of health that have festered for far too long, leading to intolerable differences in health outcomes based on accidents of birth, and amplified by racism.

As the table on stage slowly filled in, an amazing picture took shape. A majority of the speakers were Black gastroenterologists and hepatologists, and among them many were young women. As I watched the video of a group of young Black gastroenterologists and hepatologists reaching out to the community, I asked myself “Has anything like this ever happened at a major national medical association meeting in the United States? Ever?” And then it occurred to me: “And just imagine, this exactly 2 days before the 2-year anniversary of the death of George Floyd.”

The plenary session happened on May 23, and I was conscious about the dates because I will never forget that George Floyd was killed on May 25, 2020 – my 55th birthday. The juxtaposition of his death and my birthday 2 years ago shook me profoundly, prompting me to write down my reflections and my hope that, in the national reactions that followed, we were seeing the beginning of true change.2 Two years later, despite our national divisions and serious challenges, I have reasons for hope.

On May 24, I ran into a colleague who was a Black woman. I have stopped being afraid to bring up previously untouchable subjects. I asked her what she thought about the remarkable AGA Plenary. She said she was glad that she is here to see it – that her parents never got the chance.

I admitted to her that I often ask myself what more I could and should be doing. I’m trying to do what I can in recruitment, education, in my personal life. What more? She said that one thing we really need is for people who look like me to amplify the message.

So here it is: Readers, listen to the plenary talks if you were not there. At minimum, behold the following line-up of speakers and topics. Feel the history.

This was the Best of DDW 2022:

• Julius Friedenwald Recognition of Timothy Wang. – John Inadomi.
• Presidential Address: Don’t Talk: Act. The relevance of DEI to gastroenterologists and hepatologists and the imperative for action. – John Inadomi.
• AGA Equity Project: Accomplishments and what lies ahead. – Byron L. Cryer, Sandra M. Quezada.
• The genesis and goals of the Association of Black Gastroenterologists and Hepatologists. – Sophie M. Balzora.
• Increasing racial and ethnic diversity in clinical trials: What we need to do. – Monica Webb Hooper.
• Reducing disparities in colorectal cancer. – Rachel Blankson Issaka.
• Reducing disparities in liver disease. – Lauren Nephew.
• Reducing disparities in IBD. – Fernando Velayos.

Uri Ladabaum, MD, MS, is with the division of gastroenterology and hepatology in the department of medicine at Stanford (Calif.) University. He reports serving on the advisory board for UniversalDx and Lean Medical and as a consultant for Medtronic, Clinical Genomics, Guardant Health, and Freenome. Dr. Ladabaum made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

References

1. Inadomi JM. Gastroenterology. 2022 Jun;162(7):1855-7.

2. Ladabaum U. Ann Intern Med. 2020 Dec 1;173(11):938-9.

Assessing how race and other characteristics may impact the presentation and outcomes of patients with inflammatory bowel disease (IBD) is a powerful method for understanding the basic underpinnings of IBD (microbiome, environmental, immune, and genetic). Yet, exclusively viewing race with this biologic lens leaves out another critical explanation for potential differences in IBD presentation and outcomes, which is health disparities.

Health disparities are a specific type of health difference, linked with economic, social, or environmental disadvantages and in groups traditionally subjected to discrimination, exclusion, or disadvantages. These social determinants of health can, many times, have an even greater effect on disease presentation and outcomes than biological determinants. In the field of IBD, racial disparities are an underrecognized and understudied area. Yet what we do know is enough to demonstrate that critical disparities in IBD exist and that additional study and action are needed.

For example, surgery is more common in African Americans and Hispanics compared to Whites with IBD.¹ Despite these findings, African Americans and Hispanics tend to have low use of biologics early in the disease course. Surgical outcomes are also worse in African Americans and Hispanics, who experience increased morbidity, mortality, and readmission after surgery.²

While the above outcomes may be attributable to inherent biologic differences, disparities quite likely have an important role. African Americans for example are less likely to see a GI or IBD specialist, more likely use the emergency room for their IBD care, and more likely to delay health visits because of transportation and financial issues. Non-Whites are more often seen in low–IBD volume hospitals, which can affect surgical outcomes. African Americans and Hispanics more often have reduced health literacy, which could affect their confidence and understanding in starting biologic therapy.

Fortunately, understanding and eliminating disparities in IBD is increasingly recognized as a priority area for research and action by the AGA and funding societies. We can do our part in many ways. We can immediately impact what is in our control right now (asking patients what economic and social barriers they may have to accessing care). We can advocate where we may not have direct control (policies that improve health access and social determinants of health). Finally, we can better understand and study social determinants of health in our research to get a more complete picture of how health disparities affect IBD presentation and outcomes.

Dr. Velayos is chief of gastroenterology at San Francisco Medical Center of the Permanente Medical Group, regional lead for inflammatory bowel disease for Northern California Kaiser Permanente, and chair of the immunology, microbiology, and inflammatory bowel disease section for the American Gastroenterological Association. He has no relevant conflicts to declare. Dr. Velayos made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

References

1. Shi HY et al. Clin Gastroenterol Hepatol. 2018 Feb;16(2):190-7.

2. Booth A et al. Inflamm Bowel Dis. 2021 Sep 23. doi: 10.1093/ibd/izab237.

Assessing how race and other characteristics may impact the presentation and outcomes of patients with inflammatory bowel disease (IBD) is a powerful method for understanding the basic underpinnings of IBD (microbiome, environmental, immune, and genetic). Yet, exclusively viewing race with this biologic lens leaves out another critical explanation for potential differences in IBD presentation and outcomes, which is health disparities.

Health disparities are a specific type of health difference, linked with economic, social, or environmental disadvantages and in groups traditionally subjected to discrimination, exclusion, or disadvantages. These social determinants of health can, many times, have an even greater effect on disease presentation and outcomes than biological determinants. In the field of IBD, racial disparities are an underrecognized and understudied area. Yet what we do know is enough to demonstrate that critical disparities in IBD exist and that additional study and action are needed.

For example, surgery is more common in African Americans and Hispanics compared to Whites with IBD.¹ Despite these findings, African Americans and Hispanics tend to have low use of biologics early in the disease course. Surgical outcomes are also worse in African Americans and Hispanics, who experience increased morbidity, mortality, and readmission after surgery.²

While the above outcomes may be attributable to inherent biologic differences, disparities quite likely have an important role. African Americans for example are less likely to see a GI or IBD specialist, more likely use the emergency room for their IBD care, and more likely to delay health visits because of transportation and financial issues. Non-Whites are more often seen in low–IBD volume hospitals, which can affect surgical outcomes. African Americans and Hispanics more often have reduced health literacy, which could affect their confidence and understanding in starting biologic therapy.

Fortunately, understanding and eliminating disparities in IBD is increasingly recognized as a priority area for research and action by the AGA and funding societies. We can do our part in many ways. We can immediately impact what is in our control right now (asking patients what economic and social barriers they may have to accessing care). We can advocate where we may not have direct control (policies that improve health access and social determinants of health). Finally, we can better understand and study social determinants of health in our research to get a more complete picture of how health disparities affect IBD presentation and outcomes.

Dr. Velayos is chief of gastroenterology at San Francisco Medical Center of the Permanente Medical Group, regional lead for inflammatory bowel disease for Northern California Kaiser Permanente, and chair of the immunology, microbiology, and inflammatory bowel disease section for the American Gastroenterological Association. He has no relevant conflicts to declare. Dr. Velayos made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

References

1. Shi HY et al. Clin Gastroenterol Hepatol. 2018 Feb;16(2):190-7.

2. Booth A et al. Inflamm Bowel Dis. 2021 Sep 23. doi: 10.1093/ibd/izab237.

Assessing how race and other characteristics may impact the presentation and outcomes of patients with inflammatory bowel disease (IBD) is a powerful method for understanding the basic underpinnings of IBD (microbiome, environmental, immune, and genetic). Yet, exclusively viewing race with this biologic lens leaves out another critical explanation for potential differences in IBD presentation and outcomes, which is health disparities.

Health disparities are a specific type of health difference, linked with economic, social, or environmental disadvantages and in groups traditionally subjected to discrimination, exclusion, or disadvantages. These social determinants of health can, many times, have an even greater effect on disease presentation and outcomes than biological determinants. In the field of IBD, racial disparities are an underrecognized and understudied area. Yet what we do know is enough to demonstrate that critical disparities in IBD exist and that additional study and action are needed.

For example, surgery is more common in African Americans and Hispanics compared to Whites with IBD.¹ Despite these findings, African Americans and Hispanics tend to have low use of biologics early in the disease course. Surgical outcomes are also worse in African Americans and Hispanics, who experience increased morbidity, mortality, and readmission after surgery.²

While the above outcomes may be attributable to inherent biologic differences, disparities quite likely have an important role. African Americans for example are less likely to see a GI or IBD specialist, more likely use the emergency room for their IBD care, and more likely to delay health visits because of transportation and financial issues. Non-Whites are more often seen in low–IBD volume hospitals, which can affect surgical outcomes. African Americans and Hispanics more often have reduced health literacy, which could affect their confidence and understanding in starting biologic therapy.

Fortunately, understanding and eliminating disparities in IBD is increasingly recognized as a priority area for research and action by the AGA and funding societies. We can do our part in many ways. We can immediately impact what is in our control right now (asking patients what economic and social barriers they may have to accessing care). We can advocate where we may not have direct control (policies that improve health access and social determinants of health). Finally, we can better understand and study social determinants of health in our research to get a more complete picture of how health disparities affect IBD presentation and outcomes.

Dr. Velayos is chief of gastroenterology at San Francisco Medical Center of the Permanente Medical Group, regional lead for inflammatory bowel disease for Northern California Kaiser Permanente, and chair of the immunology, microbiology, and inflammatory bowel disease section for the American Gastroenterological Association. He has no relevant conflicts to declare. Dr. Velayos made these comments during the AGA Institute Presidential Plenary at the annual Digestive Disease Week®.

References

1. Shi HY et al. Clin Gastroenterol Hepatol. 2018 Feb;16(2):190-7.

2. Booth A et al. Inflamm Bowel Dis. 2021 Sep 23. doi: 10.1093/ibd/izab237.