Sharon Worcester

Enrollment in a supportive oncodermatology program was associated with improved quality of life in patients who experienced dermatologic effects from cancer therapy, according to a cross-sectional survey of participants.

The average quality of life score prior to program participation in 34 adult patients enrolled in the George Washington University Supportive Oncodermatology Clinic who responded to the survey was 6.5, indicating a moderate effect of their dermatologic symptoms on quality of life. After the beginning of treatment, the average score declined significantly to 3.8, indicating a small effect of the symptoms on quality of life, Leora Aizman, a medical student at George Washington University, Washington, and colleagues reported in the Journal of Drugs in Dermatology.

“On average, [quality of life] total scores were significantly reduced by 2.7 points after joining the supportive oncodermatology clinic,” the authors wrote.

Decreases were seen across all quality of life categories, including physical symptoms, embarrassment, clothes, social/leisure, work/school, and close relationships; the only score that didn’t decrease significantly was for physical symptoms of itch, pain, or soreness (1.43 vs. 1.1 before and after therapy), whereas the category that showed the greatest difference was embarrassment about the dermatologic condition (1.57 vs. 0.83 before and after therapy).

As for satisfaction with the program, the average participant satisfaction score was 4.15, indicating satisfaction with the program. The lowest – an average of 3.67, indicating neutral to satisfied – was related to the effects of the program on treatment adherence.

Survey respondents were adults aged over 18 years who received dermatologic care between the opening of the clinic in May 2017 and Nov. 1, 2019. The online survey included questions adapted from the Dermatology Life Quality Index and Patient Satisfaction Questionnaire.

The findings, though limited by the potential for recall bias and other factors inherent in a survey-based study, suggest that participation in a comprehensive, supportive program could be of benefit for cancer patients experiencing dermatologic conditions from cancer treatment, the authors wrote, explaining that such conditions can be disabling and are associated with negative psychosocial effects. In fact, more than half of all cancer patients experience treatment interruption because of such events.

The findings also underscore the importance of a close partnerships between dermatologists and oncologists as nearly 90% of the surveyed patients were referred to the clinic by their oncologist, the authors wrote. However, the uncertainty that survey respondents experienced with respect to the effects of program participation on treatment adherence highlights a need for further study.

“Our results highlight that supportive oncodermatology interventions improve the psychosocial wellness of patients but require further research on evidence-based preventive and active management strategies,” they wrote.

Additionally, more work is needed to “optimize treatment of secondary toxicities and allow for the continuation of life-prolonging anticancer therapy,” they noted, adding that “prospective, multicenter studies on the management of [dermatologic adverse events] are critical to better understand the effectiveness of these clinics.”

This study was funded by a La Roche–Posay grant. Ms. Aizman reported having no disclosures. One coauthor reported relationships involving consulting and/or honoraria with several companies, including La Roche–Posay.

[email protected]

SOURCE: Aizman L et al. J Drugs Dermatol. 2020 Apr 17. doi: 10.36849/JDD.2020.5040.

Enrollment in a supportive oncodermatology program was associated with improved quality of life in patients who experienced dermatologic effects from cancer therapy, according to a cross-sectional survey of participants.

The average quality of life score prior to program participation in 34 adult patients enrolled in the George Washington University Supportive Oncodermatology Clinic who responded to the survey was 6.5, indicating a moderate effect of their dermatologic symptoms on quality of life. After the beginning of treatment, the average score declined significantly to 3.8, indicating a small effect of the symptoms on quality of life, Leora Aizman, a medical student at George Washington University, Washington, and colleagues reported in the Journal of Drugs in Dermatology.

“On average, [quality of life] total scores were significantly reduced by 2.7 points after joining the supportive oncodermatology clinic,” the authors wrote.

Decreases were seen across all quality of life categories, including physical symptoms, embarrassment, clothes, social/leisure, work/school, and close relationships; the only score that didn’t decrease significantly was for physical symptoms of itch, pain, or soreness (1.43 vs. 1.1 before and after therapy), whereas the category that showed the greatest difference was embarrassment about the dermatologic condition (1.57 vs. 0.83 before and after therapy).

As for satisfaction with the program, the average participant satisfaction score was 4.15, indicating satisfaction with the program. The lowest – an average of 3.67, indicating neutral to satisfied – was related to the effects of the program on treatment adherence.

Survey respondents were adults aged over 18 years who received dermatologic care between the opening of the clinic in May 2017 and Nov. 1, 2019. The online survey included questions adapted from the Dermatology Life Quality Index and Patient Satisfaction Questionnaire.

The findings, though limited by the potential for recall bias and other factors inherent in a survey-based study, suggest that participation in a comprehensive, supportive program could be of benefit for cancer patients experiencing dermatologic conditions from cancer treatment, the authors wrote, explaining that such conditions can be disabling and are associated with negative psychosocial effects. In fact, more than half of all cancer patients experience treatment interruption because of such events.

The findings also underscore the importance of a close partnerships between dermatologists and oncologists as nearly 90% of the surveyed patients were referred to the clinic by their oncologist, the authors wrote. However, the uncertainty that survey respondents experienced with respect to the effects of program participation on treatment adherence highlights a need for further study.

“Our results highlight that supportive oncodermatology interventions improve the psychosocial wellness of patients but require further research on evidence-based preventive and active management strategies,” they wrote.

Additionally, more work is needed to “optimize treatment of secondary toxicities and allow for the continuation of life-prolonging anticancer therapy,” they noted, adding that “prospective, multicenter studies on the management of [dermatologic adverse events] are critical to better understand the effectiveness of these clinics.”

This study was funded by a La Roche–Posay grant. Ms. Aizman reported having no disclosures. One coauthor reported relationships involving consulting and/or honoraria with several companies, including La Roche–Posay.

[email protected]

SOURCE: Aizman L et al. J Drugs Dermatol. 2020 Apr 17. doi: 10.36849/JDD.2020.5040.

Enrollment in a supportive oncodermatology program was associated with improved quality of life in patients who experienced dermatologic effects from cancer therapy, according to a cross-sectional survey of participants.

The average quality of life score prior to program participation in 34 adult patients enrolled in the George Washington University Supportive Oncodermatology Clinic who responded to the survey was 6.5, indicating a moderate effect of their dermatologic symptoms on quality of life. After the beginning of treatment, the average score declined significantly to 3.8, indicating a small effect of the symptoms on quality of life, Leora Aizman, a medical student at George Washington University, Washington, and colleagues reported in the Journal of Drugs in Dermatology.

“On average, [quality of life] total scores were significantly reduced by 2.7 points after joining the supportive oncodermatology clinic,” the authors wrote.

Decreases were seen across all quality of life categories, including physical symptoms, embarrassment, clothes, social/leisure, work/school, and close relationships; the only score that didn’t decrease significantly was for physical symptoms of itch, pain, or soreness (1.43 vs. 1.1 before and after therapy), whereas the category that showed the greatest difference was embarrassment about the dermatologic condition (1.57 vs. 0.83 before and after therapy).

As for satisfaction with the program, the average participant satisfaction score was 4.15, indicating satisfaction with the program. The lowest – an average of 3.67, indicating neutral to satisfied – was related to the effects of the program on treatment adherence.

Survey respondents were adults aged over 18 years who received dermatologic care between the opening of the clinic in May 2017 and Nov. 1, 2019. The online survey included questions adapted from the Dermatology Life Quality Index and Patient Satisfaction Questionnaire.

The findings, though limited by the potential for recall bias and other factors inherent in a survey-based study, suggest that participation in a comprehensive, supportive program could be of benefit for cancer patients experiencing dermatologic conditions from cancer treatment, the authors wrote, explaining that such conditions can be disabling and are associated with negative psychosocial effects. In fact, more than half of all cancer patients experience treatment interruption because of such events.

The findings also underscore the importance of a close partnerships between dermatologists and oncologists as nearly 90% of the surveyed patients were referred to the clinic by their oncologist, the authors wrote. However, the uncertainty that survey respondents experienced with respect to the effects of program participation on treatment adherence highlights a need for further study.

“Our results highlight that supportive oncodermatology interventions improve the psychosocial wellness of patients but require further research on evidence-based preventive and active management strategies,” they wrote.

Additionally, more work is needed to “optimize treatment of secondary toxicities and allow for the continuation of life-prolonging anticancer therapy,” they noted, adding that “prospective, multicenter studies on the management of [dermatologic adverse events] are critical to better understand the effectiveness of these clinics.”

This study was funded by a La Roche–Posay grant. Ms. Aizman reported having no disclosures. One coauthor reported relationships involving consulting and/or honoraria with several companies, including La Roche–Posay.

[email protected]

SOURCE: Aizman L et al. J Drugs Dermatol. 2020 Apr 17. doi: 10.36849/JDD.2020.5040.

The Food and Drug Administration has expanded the indication for ibrutinib (Imbruvica) to allow its combination with rituximab for frontline treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adults.

The approval, announced April 21, was based on findings from the randomized, controlled, open-label, phase 3 E1912 trial of 529 patients, which demonstrated significantly improved progression-free survival (PFS) among those who received ibrutinib plus rituximab, compared with those who received fludarabine, cyclophosphamide, and rituximab (FCR) (87% vs. 75%; hazard ratio, 0.34). Median PFS was not reached in either arm after a median follow-up of 37 months.

E1912 was the first study to show superiority of a chemotherapy-free regimen over FCR chemoimmunotherapy, considered the gold standard for newly diagnosed CLL and SLL for the past 2 decades.

The recommended dosage for the newly approved combination is a once-daily 420-mg dose of ibrutinib taken with a glass of water, with rituximab initiation in the second cycle at doses of 50 mg/m2 on day 1, 325 mg/m2 on day 2, and 500 mg/m2 on days 1-5 of subsequent cycles for a total of six cycles.

This approval marks the 11th for ibrutinib across six disease areas, and its 6th in CLL.

[email protected]

The Food and Drug Administration has expanded the indication for ibrutinib (Imbruvica) to allow its combination with rituximab for frontline treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adults.

The approval, announced April 21, was based on findings from the randomized, controlled, open-label, phase 3 E1912 trial of 529 patients, which demonstrated significantly improved progression-free survival (PFS) among those who received ibrutinib plus rituximab, compared with those who received fludarabine, cyclophosphamide, and rituximab (FCR) (87% vs. 75%; hazard ratio, 0.34). Median PFS was not reached in either arm after a median follow-up of 37 months.

E1912 was the first study to show superiority of a chemotherapy-free regimen over FCR chemoimmunotherapy, considered the gold standard for newly diagnosed CLL and SLL for the past 2 decades.

The recommended dosage for the newly approved combination is a once-daily 420-mg dose of ibrutinib taken with a glass of water, with rituximab initiation in the second cycle at doses of 50 mg/m2 on day 1, 325 mg/m2 on day 2, and 500 mg/m2 on days 1-5 of subsequent cycles for a total of six cycles.

This approval marks the 11th for ibrutinib across six disease areas, and its 6th in CLL.

[email protected]

The Food and Drug Administration has expanded the indication for ibrutinib (Imbruvica) to allow its combination with rituximab for frontline treatment of chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) in adults.

The approval, announced April 21, was based on findings from the randomized, controlled, open-label, phase 3 E1912 trial of 529 patients, which demonstrated significantly improved progression-free survival (PFS) among those who received ibrutinib plus rituximab, compared with those who received fludarabine, cyclophosphamide, and rituximab (FCR) (87% vs. 75%; hazard ratio, 0.34). Median PFS was not reached in either arm after a median follow-up of 37 months.

E1912 was the first study to show superiority of a chemotherapy-free regimen over FCR chemoimmunotherapy, considered the gold standard for newly diagnosed CLL and SLL for the past 2 decades.

The recommended dosage for the newly approved combination is a once-daily 420-mg dose of ibrutinib taken with a glass of water, with rituximab initiation in the second cycle at doses of 50 mg/m2 on day 1, 325 mg/m2 on day 2, and 500 mg/m2 on days 1-5 of subsequent cycles for a total of six cycles.

This approval marks the 11th for ibrutinib across six disease areas, and its 6th in CLL.

[email protected]

Lung cancer patients should be prioritized for COVID-19 testing, according to an editorial published in Annals of Oncology.

In fact, treatment recommendations should call for baseline COVID-19 testing for all patients with lung cancer, Antonio Passaro, MD, PhD, of the European Institute of Oncology in Milan, Italy, and colleagues argued in the editorial.

“While all types of malignancies seem to be associated with high COVID-19 prevalence, morbidity, and mortality, lung cancer represents a specific scenario of cumulative risk factors for COVID-19 complications,” the authors wrote.

“[Lung cancer patients] are at a uniquely escalated risk of complications from COVID-19 due to the common features of smoking history, respiratory and cardiac disease, advanced age, and often predisposing risks from treatment, such as lung surgery and immunosuppressive chemotherapy,” said Howard (Jack) West, MD, of City of Hope Comprehensive Cancer Center in Duarte, Calif., who was not involved in the editorial.

“They also routinely experience a cough as well as chest imaging that may overlap between their underlying lung cancer, possible side effects of treatment, and potential COVID-19, leading to troubling ambiguity that can only be addressed by proactive and widespread testing of patients with lung cancer at the earliest opportunity and as a very high priority,” Dr. West added.

Dr. Passaro and colleagues’ editorial outlined these and other issues that suggest a need to prioritize testing in lung cancer patients.

Disease characteristics, treatment, and imaging

Lung cancer patients may have “defective pulmonary architecture,” such as mechanical obstruction from a tumor or previous lung surgery, that predisposes them to infection and can increase the risk of cytokine release. This is a concern because massive cytokine release during SARS-CoV-2 infection “has been postulated to be the major step in leading to the development of ARDS [acute respiratory distress syndrome],” Dr. Passaro and colleagues wrote.

The authors also argued that similar clinical symptoms among lung cancer patients and those with COVID-19 – such as cough, fever, and dyspnea – underscore the need for an accurate screening model to allow for early COVID-19 detection and potentially improve outcomes.

Similarly, lung cancer patients and COVID-19 patients may have overlapping findings on imaging. The radiologic effects of some common treatments for lung cancer can lead to the same kind of ground glass opacities and other findings seen in COVID-19 patients. Therefore, the authors predict an increase in “COVID-19-suspicious imaging, even in the absence of new symptoms” in the coming weeks.

Another issue to consider is the frequent use of corticosteroids in cancer patients. Corticosteroids may be harmful when used for COVID-19–related acute respiratory distress syndrome and could mask early symptoms of infection. Therefore, routine COVID-19 testing in patients receiving steroids may be warranted, according to Dr. Passaro and colleagues.

In addition, immunosuppression associated with cancer treatment “may impose specific consideration on the schedule and dose of cytotoxic chemotherapy for lung cancer patients in epidemic areas,” the authors wrote.

Increasing awareness: A registry and guidelines

“In the era of COVID-19, the optimal management of patients with lung cancer remains unknown, and the oncology community should have increased awareness to prevent the emergence of an increase in cancer-related and infectious mortality,” Dr. Passaro and colleagues wrote.

To that end, a novel global registry (TERAVOLT) has been launched and is collecting data worldwide with an aim of developing a tailored risk assessment strategy for lung cancer patients. The authors noted that developing international consensus with respect to COVID-19 testing in lung cancer is essential for achieving that goal.

The European Society for Medical Oncology recently released guidelines for treating lung cancer patients during the COVID-19 pandemic, but those guidelines do not include recommendations on COVID-19 testing.

“Baseline SARS-CoV-2 testing for all patients affected by lung cancer should be recommended,” Dr. Passaro and colleagues wrote. “In addition, for those patients with a negative swab test and new ground glass opacities detected on CT scan, with or without new respiratory symptoms, bronchoscopy should be considered to increase testing sensitivity.”

This work was partially supported by the Italian Ministry of Health. The authors reported having no relevant conflicts of interest. Dr. West is a regular correspondent for Medscape, which is owned by the same parent company as MDedge.

[email protected]

SOURCE: Passaro A et al. Annals of Oncology. doi: 10.1016/j.annonc.2020.04.002.

Lung cancer patients should be prioritized for COVID-19 testing, according to an editorial published in Annals of Oncology.

In fact, treatment recommendations should call for baseline COVID-19 testing for all patients with lung cancer, Antonio Passaro, MD, PhD, of the European Institute of Oncology in Milan, Italy, and colleagues argued in the editorial.

“While all types of malignancies seem to be associated with high COVID-19 prevalence, morbidity, and mortality, lung cancer represents a specific scenario of cumulative risk factors for COVID-19 complications,” the authors wrote.

“[Lung cancer patients] are at a uniquely escalated risk of complications from COVID-19 due to the common features of smoking history, respiratory and cardiac disease, advanced age, and often predisposing risks from treatment, such as lung surgery and immunosuppressive chemotherapy,” said Howard (Jack) West, MD, of City of Hope Comprehensive Cancer Center in Duarte, Calif., who was not involved in the editorial.

“They also routinely experience a cough as well as chest imaging that may overlap between their underlying lung cancer, possible side effects of treatment, and potential COVID-19, leading to troubling ambiguity that can only be addressed by proactive and widespread testing of patients with lung cancer at the earliest opportunity and as a very high priority,” Dr. West added.

Dr. Passaro and colleagues’ editorial outlined these and other issues that suggest a need to prioritize testing in lung cancer patients.

Disease characteristics, treatment, and imaging

Lung cancer patients may have “defective pulmonary architecture,” such as mechanical obstruction from a tumor or previous lung surgery, that predisposes them to infection and can increase the risk of cytokine release. This is a concern because massive cytokine release during SARS-CoV-2 infection “has been postulated to be the major step in leading to the development of ARDS [acute respiratory distress syndrome],” Dr. Passaro and colleagues wrote.

The authors also argued that similar clinical symptoms among lung cancer patients and those with COVID-19 – such as cough, fever, and dyspnea – underscore the need for an accurate screening model to allow for early COVID-19 detection and potentially improve outcomes.

Similarly, lung cancer patients and COVID-19 patients may have overlapping findings on imaging. The radiologic effects of some common treatments for lung cancer can lead to the same kind of ground glass opacities and other findings seen in COVID-19 patients. Therefore, the authors predict an increase in “COVID-19-suspicious imaging, even in the absence of new symptoms” in the coming weeks.

Another issue to consider is the frequent use of corticosteroids in cancer patients. Corticosteroids may be harmful when used for COVID-19–related acute respiratory distress syndrome and could mask early symptoms of infection. Therefore, routine COVID-19 testing in patients receiving steroids may be warranted, according to Dr. Passaro and colleagues.

In addition, immunosuppression associated with cancer treatment “may impose specific consideration on the schedule and dose of cytotoxic chemotherapy for lung cancer patients in epidemic areas,” the authors wrote.

Increasing awareness: A registry and guidelines

“In the era of COVID-19, the optimal management of patients with lung cancer remains unknown, and the oncology community should have increased awareness to prevent the emergence of an increase in cancer-related and infectious mortality,” Dr. Passaro and colleagues wrote.

To that end, a novel global registry (TERAVOLT) has been launched and is collecting data worldwide with an aim of developing a tailored risk assessment strategy for lung cancer patients. The authors noted that developing international consensus with respect to COVID-19 testing in lung cancer is essential for achieving that goal.

The European Society for Medical Oncology recently released guidelines for treating lung cancer patients during the COVID-19 pandemic, but those guidelines do not include recommendations on COVID-19 testing.

“Baseline SARS-CoV-2 testing for all patients affected by lung cancer should be recommended,” Dr. Passaro and colleagues wrote. “In addition, for those patients with a negative swab test and new ground glass opacities detected on CT scan, with or without new respiratory symptoms, bronchoscopy should be considered to increase testing sensitivity.”

This work was partially supported by the Italian Ministry of Health. The authors reported having no relevant conflicts of interest. Dr. West is a regular correspondent for Medscape, which is owned by the same parent company as MDedge.

[email protected]

SOURCE: Passaro A et al. Annals of Oncology. doi: 10.1016/j.annonc.2020.04.002.

Lung cancer patients should be prioritized for COVID-19 testing, according to an editorial published in Annals of Oncology.

In fact, treatment recommendations should call for baseline COVID-19 testing for all patients with lung cancer, Antonio Passaro, MD, PhD, of the European Institute of Oncology in Milan, Italy, and colleagues argued in the editorial.

“While all types of malignancies seem to be associated with high COVID-19 prevalence, morbidity, and mortality, lung cancer represents a specific scenario of cumulative risk factors for COVID-19 complications,” the authors wrote.

“[Lung cancer patients] are at a uniquely escalated risk of complications from COVID-19 due to the common features of smoking history, respiratory and cardiac disease, advanced age, and often predisposing risks from treatment, such as lung surgery and immunosuppressive chemotherapy,” said Howard (Jack) West, MD, of City of Hope Comprehensive Cancer Center in Duarte, Calif., who was not involved in the editorial.

“They also routinely experience a cough as well as chest imaging that may overlap between their underlying lung cancer, possible side effects of treatment, and potential COVID-19, leading to troubling ambiguity that can only be addressed by proactive and widespread testing of patients with lung cancer at the earliest opportunity and as a very high priority,” Dr. West added.

Dr. Passaro and colleagues’ editorial outlined these and other issues that suggest a need to prioritize testing in lung cancer patients.

Disease characteristics, treatment, and imaging

Lung cancer patients may have “defective pulmonary architecture,” such as mechanical obstruction from a tumor or previous lung surgery, that predisposes them to infection and can increase the risk of cytokine release. This is a concern because massive cytokine release during SARS-CoV-2 infection “has been postulated to be the major step in leading to the development of ARDS [acute respiratory distress syndrome],” Dr. Passaro and colleagues wrote.

The authors also argued that similar clinical symptoms among lung cancer patients and those with COVID-19 – such as cough, fever, and dyspnea – underscore the need for an accurate screening model to allow for early COVID-19 detection and potentially improve outcomes.

Similarly, lung cancer patients and COVID-19 patients may have overlapping findings on imaging. The radiologic effects of some common treatments for lung cancer can lead to the same kind of ground glass opacities and other findings seen in COVID-19 patients. Therefore, the authors predict an increase in “COVID-19-suspicious imaging, even in the absence of new symptoms” in the coming weeks.

Another issue to consider is the frequent use of corticosteroids in cancer patients. Corticosteroids may be harmful when used for COVID-19–related acute respiratory distress syndrome and could mask early symptoms of infection. Therefore, routine COVID-19 testing in patients receiving steroids may be warranted, according to Dr. Passaro and colleagues.

In addition, immunosuppression associated with cancer treatment “may impose specific consideration on the schedule and dose of cytotoxic chemotherapy for lung cancer patients in epidemic areas,” the authors wrote.

Increasing awareness: A registry and guidelines

“In the era of COVID-19, the optimal management of patients with lung cancer remains unknown, and the oncology community should have increased awareness to prevent the emergence of an increase in cancer-related and infectious mortality,” Dr. Passaro and colleagues wrote.

To that end, a novel global registry (TERAVOLT) has been launched and is collecting data worldwide with an aim of developing a tailored risk assessment strategy for lung cancer patients. The authors noted that developing international consensus with respect to COVID-19 testing in lung cancer is essential for achieving that goal.

The European Society for Medical Oncology recently released guidelines for treating lung cancer patients during the COVID-19 pandemic, but those guidelines do not include recommendations on COVID-19 testing.

“Baseline SARS-CoV-2 testing for all patients affected by lung cancer should be recommended,” Dr. Passaro and colleagues wrote. “In addition, for those patients with a negative swab test and new ground glass opacities detected on CT scan, with or without new respiratory symptoms, bronchoscopy should be considered to increase testing sensitivity.”

This work was partially supported by the Italian Ministry of Health. The authors reported having no relevant conflicts of interest. Dr. West is a regular correspondent for Medscape, which is owned by the same parent company as MDedge.

[email protected]

SOURCE: Passaro A et al. Annals of Oncology. doi: 10.1016/j.annonc.2020.04.002.

For Luanne Freer, MD, an expert in high-altitude pulmonary edema (HAPE) and founder and director of Everest ER, a nonprofit seasonal clinic at the Mt. Everest base camp in Nepal (elevation, 17,600 ft), a sudden flurry of messages and questions she received about a possible COVID-19/HAPE link was startling.

Courtesy Rowie Ververis

“That’s why it kind of poked me in the eye,” she said, referencing her extensive experience treating HAPE, which she described as a pressure-related phenomenon. “My goodness, they are so completely different.”

Dr. Freer, an emergency physician, reached out to several pulmonary intensivists with experience treating both HAPE and COVID-19 to gauge their reactions, and within 36 hours, they had drafted their response. In the commentary, published in High Altitude Medicine & Biology, the clinicians note that the comparison between HAPE and COVID-19 is potentially risky.

“As a group of physicians who have in some cases cared for patients with COVID-19 and in all cases cared for patients with HAPE and studied its pathophysiology and management, we feel it important to correct this misconception, as continued amplification of this message could have adverse effects on management of these patients,” they wrote.

The suggestion that COVID-19 lung injury sometimes looks more like HAPE than like acute respiratory distress syndrome (ARDS) appeared in a journal review article in late March and was put forth by medical professionals on social media where it gained traction in recent weeks and was amplified in multiple media outlets, including this one.

“With COVID, we don’t understand everything that’s going on, but we know for sure it’s an inflammatory process – not a pressure-related problem,” Dr. Freer said. “I thought ... this could be so dangerous to load the medicines that we use when we’re treating HAPE onto patients with COVID-19.”

The pathophysiological mechanisms in HAPE are different than those in other respiratory syndromes, including those associated with COVID-19, said Andrew M. Luks, MD, of the UW Medicine, Seattle, and the first author on the commentary.

“HAPE is a noncardiogenic form of pulmonary edema, as are ARDS due to bacteria or viral pneumonia, re-expansion pulmonary edema, immersion pulmonary edema, negative pressure pulmonary edema, and neurogenic pulmonary edema,” Dr. Luks, Dr. Freer, and colleagues wrote in the commentary, explaining that all of these entities cause varying degrees of hypoxemia and diffuse bilateral opacities on chest imaging. “Importantly, in all of these cases, edema accumulates in the interstitial and alveolar spaces of the lung as a result of imbalance in Starling forces.”

A difference between these entities, however, is “the mechanism by which that imbalance develops,” they noted.

The excessive and uneven hypoxic pulmonary vasoconstriction that leads to a marked increase in pulmonary artery pressure, subsequent lung overperfusion, increased pulmonary capillary hydrostatic pressure, and leakage of fluid from the vascular space into the alveolar space as seen in HAPE, is a “fundamentally different phenomenon than what is seen in COVID-19-related ARDS, which involves viral-mediated inflammatory responses as the primary pathophysiological mechanism,” they added.

The authors described several other differences between the conditions, ultimately noting that “understanding the distinction between the pathophysiological mechanisms of these entities is critical for patient management.”

In HAPE, supplemental oxygen alone may be sufficient; in COVID-19, it may improve hypoxemia but won’t resolve the underlying inflammation or injury, they explained, adding that “only good supportive care including mechanical ventilation, quite often for long periods of time, allows some patients to survive until their disease resolves.”

Further, HAPE can be prevented or treated with pulmonary vasodilators such a nifedipine or sildenafil, which decrease pulmonary artery pressure and, as a result lower pulmonary capillary hydrostatic pressure, they said.

Use of such medications for COVID-19 might decrease pulmonary artery pressure and improve right ventricular function in COVID-19, but “by releasing hypoxic pulmonary vasoconstriction and increasing perfusion to nonventilated regions of the lung, they could also worsen ventilation-perfusion mismatch” and thereby worsen hypoxemia, they explained, adding that the treatments can also cause or worsen hypotension.

Efforts to share observations and experience are important in medicine, but sometimes, as in this circumstance, “they get out there, spread around – like a brushfire almost – and get [unwarranted] face validity,” Dr. Luks said, noting that in response to information circulating about COVID-19 and HAPE, he has already heard medical professionals floating the idea of treating COVID-19 with treatments used for HAPE.

It’s true that some COVID-19 lung injury cases are behaving differently than typical ARDS, he said, adding that presentation can vary.

“But trying to equate HAPE and COVID-19 is just wrong,” he said. “HAPE and COVID-19 may share several features ...but those are features that are shared by a lot of different forms of respiratory failure.”

In a recent video interview, WebMD’s chief medical officer John Whyte, MD, spoke with a New York City physician trained in critical care and emergency medicine, Cameron Kyle-Sidell, MD, who raised the need to consider different respiratory protocols for COVID-19, noting that standard protocols were falling short in many cases.

“What we’re seeing ... is something unusual, it’s something that we are not used to,” Dr. Kyle-Sidell of Maimonides Medical Center said in that interview, stressing that the presentation differed from that seen in typical ARDS. “The patterns I was seeing did not make sense.”

Like others, he noted that COVID-19 patients were presenting with illness that clinically looked more like HAPE, but that the pathophysiology is not necessary similar to HAPE.

At around the same time, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues, published a letter to the editor in the American Journal of Respiratory and Critical Care Medicine stressing that the ARDS presentation in COVID-19 patients is atypical and requires a patient physiology–driven treatment approach, rather than a standard protocol–driven approach. Dr. Gattinoni and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation.

Dr. Luks agreed that “some patients with COVID-19 do not have the same physiologic derangements that we see in a lot of other people with ARDS.”

“[Dr. Gattinoni] is making the point that we need to treat these people differently ... and I think that’s a valid point, and honestly, that’s a point that applied even before COVID-19,” he said. “Most of the things that we see in clinical practice – there’s a lot of heterogeneity between patients, and you have to be prepared to tailor your therapy in light of the differences that you’re picking up from your observations at the bedside and other data that you’re getting on the patient.”

The main concern Dr. Luks and his coauthors wanted to convey, they said, is making sure that the anecdotal experiences and observations of clinicians struggling to find answers don’t spiral out of control without proper vetting, thereby leading to patient harm.

“In this challenging time, we must identify the best means to care for these critically ill patients. That approach should be grounded in sound pulmonary physiology, clinical experience and, when available, evidence from clinical studies,” they concluded.

Dr. Luks and Dr. Freer reported having no financial disclosures.

[email protected]

For Luanne Freer, MD, an expert in high-altitude pulmonary edema (HAPE) and founder and director of Everest ER, a nonprofit seasonal clinic at the Mt. Everest base camp in Nepal (elevation, 17,600 ft), a sudden flurry of messages and questions she received about a possible COVID-19/HAPE link was startling.

Courtesy Rowie Ververis

“That’s why it kind of poked me in the eye,” she said, referencing her extensive experience treating HAPE, which she described as a pressure-related phenomenon. “My goodness, they are so completely different.”

Dr. Freer, an emergency physician, reached out to several pulmonary intensivists with experience treating both HAPE and COVID-19 to gauge their reactions, and within 36 hours, they had drafted their response. In the commentary, published in High Altitude Medicine & Biology, the clinicians note that the comparison between HAPE and COVID-19 is potentially risky.

“As a group of physicians who have in some cases cared for patients with COVID-19 and in all cases cared for patients with HAPE and studied its pathophysiology and management, we feel it important to correct this misconception, as continued amplification of this message could have adverse effects on management of these patients,” they wrote.

The suggestion that COVID-19 lung injury sometimes looks more like HAPE than like acute respiratory distress syndrome (ARDS) appeared in a journal review article in late March and was put forth by medical professionals on social media where it gained traction in recent weeks and was amplified in multiple media outlets, including this one.

“With COVID, we don’t understand everything that’s going on, but we know for sure it’s an inflammatory process – not a pressure-related problem,” Dr. Freer said. “I thought ... this could be so dangerous to load the medicines that we use when we’re treating HAPE onto patients with COVID-19.”

The pathophysiological mechanisms in HAPE are different than those in other respiratory syndromes, including those associated with COVID-19, said Andrew M. Luks, MD, of the UW Medicine, Seattle, and the first author on the commentary.

“HAPE is a noncardiogenic form of pulmonary edema, as are ARDS due to bacteria or viral pneumonia, re-expansion pulmonary edema, immersion pulmonary edema, negative pressure pulmonary edema, and neurogenic pulmonary edema,” Dr. Luks, Dr. Freer, and colleagues wrote in the commentary, explaining that all of these entities cause varying degrees of hypoxemia and diffuse bilateral opacities on chest imaging. “Importantly, in all of these cases, edema accumulates in the interstitial and alveolar spaces of the lung as a result of imbalance in Starling forces.”

A difference between these entities, however, is “the mechanism by which that imbalance develops,” they noted.

The excessive and uneven hypoxic pulmonary vasoconstriction that leads to a marked increase in pulmonary artery pressure, subsequent lung overperfusion, increased pulmonary capillary hydrostatic pressure, and leakage of fluid from the vascular space into the alveolar space as seen in HAPE, is a “fundamentally different phenomenon than what is seen in COVID-19-related ARDS, which involves viral-mediated inflammatory responses as the primary pathophysiological mechanism,” they added.

The authors described several other differences between the conditions, ultimately noting that “understanding the distinction between the pathophysiological mechanisms of these entities is critical for patient management.”

In HAPE, supplemental oxygen alone may be sufficient; in COVID-19, it may improve hypoxemia but won’t resolve the underlying inflammation or injury, they explained, adding that “only good supportive care including mechanical ventilation, quite often for long periods of time, allows some patients to survive until their disease resolves.”

Further, HAPE can be prevented or treated with pulmonary vasodilators such a nifedipine or sildenafil, which decrease pulmonary artery pressure and, as a result lower pulmonary capillary hydrostatic pressure, they said.

Use of such medications for COVID-19 might decrease pulmonary artery pressure and improve right ventricular function in COVID-19, but “by releasing hypoxic pulmonary vasoconstriction and increasing perfusion to nonventilated regions of the lung, they could also worsen ventilation-perfusion mismatch” and thereby worsen hypoxemia, they explained, adding that the treatments can also cause or worsen hypotension.

Efforts to share observations and experience are important in medicine, but sometimes, as in this circumstance, “they get out there, spread around – like a brushfire almost – and get [unwarranted] face validity,” Dr. Luks said, noting that in response to information circulating about COVID-19 and HAPE, he has already heard medical professionals floating the idea of treating COVID-19 with treatments used for HAPE.

It’s true that some COVID-19 lung injury cases are behaving differently than typical ARDS, he said, adding that presentation can vary.

“But trying to equate HAPE and COVID-19 is just wrong,” he said. “HAPE and COVID-19 may share several features ...but those are features that are shared by a lot of different forms of respiratory failure.”

In a recent video interview, WebMD’s chief medical officer John Whyte, MD, spoke with a New York City physician trained in critical care and emergency medicine, Cameron Kyle-Sidell, MD, who raised the need to consider different respiratory protocols for COVID-19, noting that standard protocols were falling short in many cases.

“What we’re seeing ... is something unusual, it’s something that we are not used to,” Dr. Kyle-Sidell of Maimonides Medical Center said in that interview, stressing that the presentation differed from that seen in typical ARDS. “The patterns I was seeing did not make sense.”

Like others, he noted that COVID-19 patients were presenting with illness that clinically looked more like HAPE, but that the pathophysiology is not necessary similar to HAPE.

At around the same time, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues, published a letter to the editor in the American Journal of Respiratory and Critical Care Medicine stressing that the ARDS presentation in COVID-19 patients is atypical and requires a patient physiology–driven treatment approach, rather than a standard protocol–driven approach. Dr. Gattinoni and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation.

Dr. Luks agreed that “some patients with COVID-19 do not have the same physiologic derangements that we see in a lot of other people with ARDS.”

“[Dr. Gattinoni] is making the point that we need to treat these people differently ... and I think that’s a valid point, and honestly, that’s a point that applied even before COVID-19,” he said. “Most of the things that we see in clinical practice – there’s a lot of heterogeneity between patients, and you have to be prepared to tailor your therapy in light of the differences that you’re picking up from your observations at the bedside and other data that you’re getting on the patient.”

The main concern Dr. Luks and his coauthors wanted to convey, they said, is making sure that the anecdotal experiences and observations of clinicians struggling to find answers don’t spiral out of control without proper vetting, thereby leading to patient harm.

“In this challenging time, we must identify the best means to care for these critically ill patients. That approach should be grounded in sound pulmonary physiology, clinical experience and, when available, evidence from clinical studies,” they concluded.

Dr. Luks and Dr. Freer reported having no financial disclosures.

[email protected]

For Luanne Freer, MD, an expert in high-altitude pulmonary edema (HAPE) and founder and director of Everest ER, a nonprofit seasonal clinic at the Mt. Everest base camp in Nepal (elevation, 17,600 ft), a sudden flurry of messages and questions she received about a possible COVID-19/HAPE link was startling.

Courtesy Rowie Ververis

“That’s why it kind of poked me in the eye,” she said, referencing her extensive experience treating HAPE, which she described as a pressure-related phenomenon. “My goodness, they are so completely different.”

Dr. Freer, an emergency physician, reached out to several pulmonary intensivists with experience treating both HAPE and COVID-19 to gauge their reactions, and within 36 hours, they had drafted their response. In the commentary, published in High Altitude Medicine & Biology, the clinicians note that the comparison between HAPE and COVID-19 is potentially risky.

“As a group of physicians who have in some cases cared for patients with COVID-19 and in all cases cared for patients with HAPE and studied its pathophysiology and management, we feel it important to correct this misconception, as continued amplification of this message could have adverse effects on management of these patients,” they wrote.

The suggestion that COVID-19 lung injury sometimes looks more like HAPE than like acute respiratory distress syndrome (ARDS) appeared in a journal review article in late March and was put forth by medical professionals on social media where it gained traction in recent weeks and was amplified in multiple media outlets, including this one.

“With COVID, we don’t understand everything that’s going on, but we know for sure it’s an inflammatory process – not a pressure-related problem,” Dr. Freer said. “I thought ... this could be so dangerous to load the medicines that we use when we’re treating HAPE onto patients with COVID-19.”

The pathophysiological mechanisms in HAPE are different than those in other respiratory syndromes, including those associated with COVID-19, said Andrew M. Luks, MD, of the UW Medicine, Seattle, and the first author on the commentary.

“HAPE is a noncardiogenic form of pulmonary edema, as are ARDS due to bacteria or viral pneumonia, re-expansion pulmonary edema, immersion pulmonary edema, negative pressure pulmonary edema, and neurogenic pulmonary edema,” Dr. Luks, Dr. Freer, and colleagues wrote in the commentary, explaining that all of these entities cause varying degrees of hypoxemia and diffuse bilateral opacities on chest imaging. “Importantly, in all of these cases, edema accumulates in the interstitial and alveolar spaces of the lung as a result of imbalance in Starling forces.”

A difference between these entities, however, is “the mechanism by which that imbalance develops,” they noted.

The excessive and uneven hypoxic pulmonary vasoconstriction that leads to a marked increase in pulmonary artery pressure, subsequent lung overperfusion, increased pulmonary capillary hydrostatic pressure, and leakage of fluid from the vascular space into the alveolar space as seen in HAPE, is a “fundamentally different phenomenon than what is seen in COVID-19-related ARDS, which involves viral-mediated inflammatory responses as the primary pathophysiological mechanism,” they added.

The authors described several other differences between the conditions, ultimately noting that “understanding the distinction between the pathophysiological mechanisms of these entities is critical for patient management.”

In HAPE, supplemental oxygen alone may be sufficient; in COVID-19, it may improve hypoxemia but won’t resolve the underlying inflammation or injury, they explained, adding that “only good supportive care including mechanical ventilation, quite often for long periods of time, allows some patients to survive until their disease resolves.”

Further, HAPE can be prevented or treated with pulmonary vasodilators such a nifedipine or sildenafil, which decrease pulmonary artery pressure and, as a result lower pulmonary capillary hydrostatic pressure, they said.

Use of such medications for COVID-19 might decrease pulmonary artery pressure and improve right ventricular function in COVID-19, but “by releasing hypoxic pulmonary vasoconstriction and increasing perfusion to nonventilated regions of the lung, they could also worsen ventilation-perfusion mismatch” and thereby worsen hypoxemia, they explained, adding that the treatments can also cause or worsen hypotension.

Efforts to share observations and experience are important in medicine, but sometimes, as in this circumstance, “they get out there, spread around – like a brushfire almost – and get [unwarranted] face validity,” Dr. Luks said, noting that in response to information circulating about COVID-19 and HAPE, he has already heard medical professionals floating the idea of treating COVID-19 with treatments used for HAPE.

It’s true that some COVID-19 lung injury cases are behaving differently than typical ARDS, he said, adding that presentation can vary.

“But trying to equate HAPE and COVID-19 is just wrong,” he said. “HAPE and COVID-19 may share several features ...but those are features that are shared by a lot of different forms of respiratory failure.”

In a recent video interview, WebMD’s chief medical officer John Whyte, MD, spoke with a New York City physician trained in critical care and emergency medicine, Cameron Kyle-Sidell, MD, who raised the need to consider different respiratory protocols for COVID-19, noting that standard protocols were falling short in many cases.

“What we’re seeing ... is something unusual, it’s something that we are not used to,” Dr. Kyle-Sidell of Maimonides Medical Center said in that interview, stressing that the presentation differed from that seen in typical ARDS. “The patterns I was seeing did not make sense.”

Like others, he noted that COVID-19 patients were presenting with illness that clinically looked more like HAPE, but that the pathophysiology is not necessary similar to HAPE.

At around the same time, Luciano Gattinoni, MD, of the Medical University of Göttingen in Germany and colleagues, published a letter to the editor in the American Journal of Respiratory and Critical Care Medicine stressing that the ARDS presentation in COVID-19 patients is atypical and requires a patient physiology–driven treatment approach, rather than a standard protocol–driven approach. Dr. Gattinoni and colleagues suggested that instead of high positive end-expiratory pressure (PEEP), physicians should consider the lowest possible PEEP and gentle ventilation.

Dr. Luks agreed that “some patients with COVID-19 do not have the same physiologic derangements that we see in a lot of other people with ARDS.”

“[Dr. Gattinoni] is making the point that we need to treat these people differently ... and I think that’s a valid point, and honestly, that’s a point that applied even before COVID-19,” he said. “Most of the things that we see in clinical practice – there’s a lot of heterogeneity between patients, and you have to be prepared to tailor your therapy in light of the differences that you’re picking up from your observations at the bedside and other data that you’re getting on the patient.”

The main concern Dr. Luks and his coauthors wanted to convey, they said, is making sure that the anecdotal experiences and observations of clinicians struggling to find answers don’t spiral out of control without proper vetting, thereby leading to patient harm.

“In this challenging time, we must identify the best means to care for these critically ill patients. That approach should be grounded in sound pulmonary physiology, clinical experience and, when available, evidence from clinical studies,” they concluded.

Dr. Luks and Dr. Freer reported having no financial disclosures.

[email protected]

ORLANDO – Combination pepinemab and avelumab is well tolerated and shows antitumor activity in patients with advanced non–small cell lung cancer (NSCLC) who progressed on prior treatment, according to interim results from a phase 1b/2 trial.

Sharon Worcester/MDedge News

Treatment with pepinemab, an anti–semaphorin 4D antibody, and avelumab, a programmed death-ligand 1 (PD-L1) inhibitor, produced disease control rates of 59% in immunotherapy-resistant patients and 81% in immunotherapy-naive patients.

Michael Rahman Shafique, MD, of Moffitt Cancer Center in Tampa, Fla., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The CLASSICAL-Lung trial initially enrolled 12 immunotherapy-naive patients with stage IIIb/IV NSCLC into a dose-escalation phase that examined pepinemab at doses of 5, 10, and 20 mg/kg along with 10 mg/kg of avelumab every 2 weeks.

Then, the trial enrolled 50 stage IIIb/IV patients – including 18 immunotherapy-naive patients and 32 who failed prior immunotherapy – into a phase 2 dose-expansion phase.

The 10 mg/kg pepinemab dose and 10 mg/kg avelumab dose were selected for the expansion phase based on the dose-escalation results, Dr. Shafique said. He explained that all three doses were safe, but “we were saturating the target at the 10-mg dose.”
 

Efficacy and safety

“In general, the safety data were encouraging,” Dr. Shafique said. “This was a very well-tolerated combination with no concerning safety signals. The most common adverse events were grade 1 and grade 2 fatigue, chills, pyrexia, and no grade 5 events attributable to the combination were reported.”

In the efficacy analysis, there were 29 evaluable patients who received pepinemab and avelumab after progressing on prior immunotherapy and were followed for at least 6 months. Two of these patients experienced a confirmed partial response (PR), and 15 had stable disease, for a disease control rate of 59%. Five patients had durable clinical benefit lasting at least 23 weeks, and three remained on active treatment at last follow-up, including one who had been on treatment for more than a year.

Of 21 evaluable immunotherapy-naive patients followed for at least 6 months, 5 experienced a confirmed PR, and 12 had stable disease, for a disease control rate of 81%. Three patients had clinical benefit lasting at least a year, and two remained on study and continued to receive treatment at last follow-up.

Pre- and on-treatment biopsies performed on the same lesion about 5 weeks apart demonstrated “a pretty drastic reduction in viable tumor,” Dr. Shafique noted.

“Even in patients with stable disease, many of them had absent tumor on these repeat, on-treatment biopsies,” he said, also noting that CD8-positive T-cell density increased in most tumors following treatment in patients who had a PR or stable disease, and the levels appeared to correspond with response.
 

Mechanism of action

Despite advances in immunotherapy, NSCLC patients often are refractory or acquire resistance to currently available agents, but semaphorin 4D “seems to shift the balance in the microenvironment to one of myeloid-induced immune suppression and generally a protumor, if you will, microenvironment,” Dr. Shafique said.

“Blockade of semaphorin 4D with pepinemab, we think, helps relieve this suppressive environment and actually seems to stimulate infiltration of T cells and improve T-cell activity in these tumors,” he added. He went on to explain that the mechanism of action is believed to generally be through suppression of myeloid cell trafficking to the tumor and myeloid cell cytokine secretion.

Further, and more importantly for cancer immunotherapy, preclinical models suggest that anti–semaphorin 4D antibodies are synergistic with various checkpoint inhibitors, including the PD-L1 inhibitor avelumab and others, Dr. Shafique said.

Indeed, these early CLASSICAL-Lung trial findings “do support the mechanism of action being reversing this myeloid-induced suppression in the microenvironment and improving T-cell infiltration and activity,” and they support a potential benefit of combining anti–semaphorin 4D antibodies and checkpoint inhibition in advanced NSCLC after progression on prior therapy, Dr. Shafique added.

Sharon Worcester/MDedge News

Invited discussant Timothy A. Yap, MBBS, of the University of Texas MD Anderson Cancer Center in Houston, said that “inhibition of [semaphorin 4D] promotes functional immune infiltration into the [tumor microenvironment] and, therefore, is a rational way of inhibiting tumor progression” in NSCLC and other cancers.

The CLASSICAL-Lung trial “didn’t escalate all the way to the [maximum tolerated dose] but did demonstrate durable on-treatment increases in CD8-positive T-cell infiltration, including in 79% of patients with low or null PD-L1 expression, as proof of mechanism,” Dr. Yap said, noting the responses in both immunotherapy-naive and immunotherapy-resistant patients.

“So I guess the key question will be, ‘Is this an active combination in NSCLC?’ ” Dr. Yap said. “In my opinion, yes it is, but is it going to be enough to take it past registration?”
 

Next steps

As next steps for the investigators, Dr. Yap suggested looking at a more specific population of PD-L1–low or –null immunotherapy-resistant NSCLC patients, considering adding a chemotherapy agent to the pepinemab/avelumab combination, or perhaps going “straight to a randomized phase 2/3 trial [comparing the combination with] pembrolizumab.”

“The investigators should also consider other tumor types beyond non–small cell lung cancer with this particular combination,” he said.

The preclinical data with respect to the anti–semaphorin 4D antibody suggest that study in combination with other agents, such as anti–CTLA-4 agents or anti-LAG3 agents, is also warranted, Dr. Yap added, noting that triplet combinations might also be worth investigating.

The CLASSICAL-Lung trial is funded by Vaccinex and Merck. Dr. Shafique reported a consulting or advisory role with GlaxoSmithKline. Dr. Yap reported relationships with numerous pharmaceutical companies, including Merck. MD Anderson’s Institute of Applied Cancer Science, where Dr. Yap serves as medical director, has a commercial interest in DNA damage response inhibitors and other inhibitors.

[email protected]

SOURCE: Shafique MR et al. ASCO-SITC 2020, Abstract 75.

ORLANDO – Combination pepinemab and avelumab is well tolerated and shows antitumor activity in patients with advanced non–small cell lung cancer (NSCLC) who progressed on prior treatment, according to interim results from a phase 1b/2 trial.

Sharon Worcester/MDedge News

Treatment with pepinemab, an anti–semaphorin 4D antibody, and avelumab, a programmed death-ligand 1 (PD-L1) inhibitor, produced disease control rates of 59% in immunotherapy-resistant patients and 81% in immunotherapy-naive patients.

Michael Rahman Shafique, MD, of Moffitt Cancer Center in Tampa, Fla., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The CLASSICAL-Lung trial initially enrolled 12 immunotherapy-naive patients with stage IIIb/IV NSCLC into a dose-escalation phase that examined pepinemab at doses of 5, 10, and 20 mg/kg along with 10 mg/kg of avelumab every 2 weeks.

Then, the trial enrolled 50 stage IIIb/IV patients – including 18 immunotherapy-naive patients and 32 who failed prior immunotherapy – into a phase 2 dose-expansion phase.

The 10 mg/kg pepinemab dose and 10 mg/kg avelumab dose were selected for the expansion phase based on the dose-escalation results, Dr. Shafique said. He explained that all three doses were safe, but “we were saturating the target at the 10-mg dose.”
 

Efficacy and safety

“In general, the safety data were encouraging,” Dr. Shafique said. “This was a very well-tolerated combination with no concerning safety signals. The most common adverse events were grade 1 and grade 2 fatigue, chills, pyrexia, and no grade 5 events attributable to the combination were reported.”

In the efficacy analysis, there were 29 evaluable patients who received pepinemab and avelumab after progressing on prior immunotherapy and were followed for at least 6 months. Two of these patients experienced a confirmed partial response (PR), and 15 had stable disease, for a disease control rate of 59%. Five patients had durable clinical benefit lasting at least 23 weeks, and three remained on active treatment at last follow-up, including one who had been on treatment for more than a year.

Of 21 evaluable immunotherapy-naive patients followed for at least 6 months, 5 experienced a confirmed PR, and 12 had stable disease, for a disease control rate of 81%. Three patients had clinical benefit lasting at least a year, and two remained on study and continued to receive treatment at last follow-up.

Pre- and on-treatment biopsies performed on the same lesion about 5 weeks apart demonstrated “a pretty drastic reduction in viable tumor,” Dr. Shafique noted.

“Even in patients with stable disease, many of them had absent tumor on these repeat, on-treatment biopsies,” he said, also noting that CD8-positive T-cell density increased in most tumors following treatment in patients who had a PR or stable disease, and the levels appeared to correspond with response.
 

Mechanism of action

Despite advances in immunotherapy, NSCLC patients often are refractory or acquire resistance to currently available agents, but semaphorin 4D “seems to shift the balance in the microenvironment to one of myeloid-induced immune suppression and generally a protumor, if you will, microenvironment,” Dr. Shafique said.

“Blockade of semaphorin 4D with pepinemab, we think, helps relieve this suppressive environment and actually seems to stimulate infiltration of T cells and improve T-cell activity in these tumors,” he added. He went on to explain that the mechanism of action is believed to generally be through suppression of myeloid cell trafficking to the tumor and myeloid cell cytokine secretion.

Further, and more importantly for cancer immunotherapy, preclinical models suggest that anti–semaphorin 4D antibodies are synergistic with various checkpoint inhibitors, including the PD-L1 inhibitor avelumab and others, Dr. Shafique said.

Indeed, these early CLASSICAL-Lung trial findings “do support the mechanism of action being reversing this myeloid-induced suppression in the microenvironment and improving T-cell infiltration and activity,” and they support a potential benefit of combining anti–semaphorin 4D antibodies and checkpoint inhibition in advanced NSCLC after progression on prior therapy, Dr. Shafique added.

Sharon Worcester/MDedge News

Invited discussant Timothy A. Yap, MBBS, of the University of Texas MD Anderson Cancer Center in Houston, said that “inhibition of [semaphorin 4D] promotes functional immune infiltration into the [tumor microenvironment] and, therefore, is a rational way of inhibiting tumor progression” in NSCLC and other cancers.

The CLASSICAL-Lung trial “didn’t escalate all the way to the [maximum tolerated dose] but did demonstrate durable on-treatment increases in CD8-positive T-cell infiltration, including in 79% of patients with low or null PD-L1 expression, as proof of mechanism,” Dr. Yap said, noting the responses in both immunotherapy-naive and immunotherapy-resistant patients.

“So I guess the key question will be, ‘Is this an active combination in NSCLC?’ ” Dr. Yap said. “In my opinion, yes it is, but is it going to be enough to take it past registration?”
 

Next steps

As next steps for the investigators, Dr. Yap suggested looking at a more specific population of PD-L1–low or –null immunotherapy-resistant NSCLC patients, considering adding a chemotherapy agent to the pepinemab/avelumab combination, or perhaps going “straight to a randomized phase 2/3 trial [comparing the combination with] pembrolizumab.”

“The investigators should also consider other tumor types beyond non–small cell lung cancer with this particular combination,” he said.

The preclinical data with respect to the anti–semaphorin 4D antibody suggest that study in combination with other agents, such as anti–CTLA-4 agents or anti-LAG3 agents, is also warranted, Dr. Yap added, noting that triplet combinations might also be worth investigating.

The CLASSICAL-Lung trial is funded by Vaccinex and Merck. Dr. Shafique reported a consulting or advisory role with GlaxoSmithKline. Dr. Yap reported relationships with numerous pharmaceutical companies, including Merck. MD Anderson’s Institute of Applied Cancer Science, where Dr. Yap serves as medical director, has a commercial interest in DNA damage response inhibitors and other inhibitors.

[email protected]

SOURCE: Shafique MR et al. ASCO-SITC 2020, Abstract 75.

ORLANDO – Combination pepinemab and avelumab is well tolerated and shows antitumor activity in patients with advanced non–small cell lung cancer (NSCLC) who progressed on prior treatment, according to interim results from a phase 1b/2 trial.

Sharon Worcester/MDedge News

Treatment with pepinemab, an anti–semaphorin 4D antibody, and avelumab, a programmed death-ligand 1 (PD-L1) inhibitor, produced disease control rates of 59% in immunotherapy-resistant patients and 81% in immunotherapy-naive patients.

Michael Rahman Shafique, MD, of Moffitt Cancer Center in Tampa, Fla., reported these results at the ASCO-SITC Clinical Immuno-Oncology Symposium.

The CLASSICAL-Lung trial initially enrolled 12 immunotherapy-naive patients with stage IIIb/IV NSCLC into a dose-escalation phase that examined pepinemab at doses of 5, 10, and 20 mg/kg along with 10 mg/kg of avelumab every 2 weeks.

Then, the trial enrolled 50 stage IIIb/IV patients – including 18 immunotherapy-naive patients and 32 who failed prior immunotherapy – into a phase 2 dose-expansion phase.

The 10 mg/kg pepinemab dose and 10 mg/kg avelumab dose were selected for the expansion phase based on the dose-escalation results, Dr. Shafique said. He explained that all three doses were safe, but “we were saturating the target at the 10-mg dose.”
 

Efficacy and safety

“In general, the safety data were encouraging,” Dr. Shafique said. “This was a very well-tolerated combination with no concerning safety signals. The most common adverse events were grade 1 and grade 2 fatigue, chills, pyrexia, and no grade 5 events attributable to the combination were reported.”

In the efficacy analysis, there were 29 evaluable patients who received pepinemab and avelumab after progressing on prior immunotherapy and were followed for at least 6 months. Two of these patients experienced a confirmed partial response (PR), and 15 had stable disease, for a disease control rate of 59%. Five patients had durable clinical benefit lasting at least 23 weeks, and three remained on active treatment at last follow-up, including one who had been on treatment for more than a year.

Of 21 evaluable immunotherapy-naive patients followed for at least 6 months, 5 experienced a confirmed PR, and 12 had stable disease, for a disease control rate of 81%. Three patients had clinical benefit lasting at least a year, and two remained on study and continued to receive treatment at last follow-up.

Pre- and on-treatment biopsies performed on the same lesion about 5 weeks apart demonstrated “a pretty drastic reduction in viable tumor,” Dr. Shafique noted.

“Even in patients with stable disease, many of them had absent tumor on these repeat, on-treatment biopsies,” he said, also noting that CD8-positive T-cell density increased in most tumors following treatment in patients who had a PR or stable disease, and the levels appeared to correspond with response.
 

Mechanism of action

Despite advances in immunotherapy, NSCLC patients often are refractory or acquire resistance to currently available agents, but semaphorin 4D “seems to shift the balance in the microenvironment to one of myeloid-induced immune suppression and generally a protumor, if you will, microenvironment,” Dr. Shafique said.

“Blockade of semaphorin 4D with pepinemab, we think, helps relieve this suppressive environment and actually seems to stimulate infiltration of T cells and improve T-cell activity in these tumors,” he added. He went on to explain that the mechanism of action is believed to generally be through suppression of myeloid cell trafficking to the tumor and myeloid cell cytokine secretion.

Further, and more importantly for cancer immunotherapy, preclinical models suggest that anti–semaphorin 4D antibodies are synergistic with various checkpoint inhibitors, including the PD-L1 inhibitor avelumab and others, Dr. Shafique said.

Indeed, these early CLASSICAL-Lung trial findings “do support the mechanism of action being reversing this myeloid-induced suppression in the microenvironment and improving T-cell infiltration and activity,” and they support a potential benefit of combining anti–semaphorin 4D antibodies and checkpoint inhibition in advanced NSCLC after progression on prior therapy, Dr. Shafique added.

Sharon Worcester/MDedge News

Invited discussant Timothy A. Yap, MBBS, of the University of Texas MD Anderson Cancer Center in Houston, said that “inhibition of [semaphorin 4D] promotes functional immune infiltration into the [tumor microenvironment] and, therefore, is a rational way of inhibiting tumor progression” in NSCLC and other cancers.

The CLASSICAL-Lung trial “didn’t escalate all the way to the [maximum tolerated dose] but did demonstrate durable on-treatment increases in CD8-positive T-cell infiltration, including in 79% of patients with low or null PD-L1 expression, as proof of mechanism,” Dr. Yap said, noting the responses in both immunotherapy-naive and immunotherapy-resistant patients.

“So I guess the key question will be, ‘Is this an active combination in NSCLC?’ ” Dr. Yap said. “In my opinion, yes it is, but is it going to be enough to take it past registration?”
 

Next steps

As next steps for the investigators, Dr. Yap suggested looking at a more specific population of PD-L1–low or –null immunotherapy-resistant NSCLC patients, considering adding a chemotherapy agent to the pepinemab/avelumab combination, or perhaps going “straight to a randomized phase 2/3 trial [comparing the combination with] pembrolizumab.”

“The investigators should also consider other tumor types beyond non–small cell lung cancer with this particular combination,” he said.

The preclinical data with respect to the anti–semaphorin 4D antibody suggest that study in combination with other agents, such as anti–CTLA-4 agents or anti-LAG3 agents, is also warranted, Dr. Yap added, noting that triplet combinations might also be worth investigating.

The CLASSICAL-Lung trial is funded by Vaccinex and Merck. Dr. Shafique reported a consulting or advisory role with GlaxoSmithKline. Dr. Yap reported relationships with numerous pharmaceutical companies, including Merck. MD Anderson’s Institute of Applied Cancer Science, where Dr. Yap serves as medical director, has a commercial interest in DNA damage response inhibitors and other inhibitors.

[email protected]

SOURCE: Shafique MR et al. ASCO-SITC 2020, Abstract 75.

Nearly 700 women died from pregnancy-related complications in the United States in 2018, and almost a third of those deaths were associated with cardiovascular disease, according to the latest data from the Centers for Disease Control and Prevention.

Strikingly, studies suggest that up to half of cardiovascular disease–related maternal deaths are preventable, yet CVD remains the leading cause of maternal morbidity and mortality – and the incidence has been rising steadily for 2 decades.

The American College of Obstetricians and Gynecologists says that acquired heart disease is the likely culprit in the rise in incidence of maternal mortality as women enter pregnancy with an increasingly heavy burden of CVD risk factors, including older age, obesity, diabetes, and hypertension.

“They are entering pregnancy while already at risk, and that has led to an increase in morbidity and mortality during pregnancy,” Renee Patrice Bullock-Palmer, MD, a cardiologist and director of the Women’s Heart Center at Deborah Heart and Lung Center in Browns Mills, N.J., explained in an interview. “Unfortunately, among developed countries, the U.S. has the highest rates of maternal morbidity and mortality, and that’s shocking.”

It’s a problem that requires collaboration between obstetricians, cardiologists, and others involved in the care of pregnant women, she said.
 

The data and the depth of the crisis

The maternal mortality rate in 1987 – the year the CDC’s Pregnancy Mortality Surveillance System was implemented – was 7.2 per 100,000 live births. The rate in 2016 was more than double that at 16.9, and the rate in 2018, the most recent year for which data are available, was 17.4 – and significant racial and ethnic disparities in those rates have persisted over time.

In an August 2019 article published on the American Heart Association website, Dr. Bullock-Palmer addressed the cardiovascular state of health for pregnant women and the role of the cardiologists in their care, noting that there is a “role for increased collaboration between the cardiologist and the obstetrician with regards to a pregnancy heart team.”

“It is vital that mothers who are at increased risk for CVD or have established CVD be referred to a cardiologist for cardiovascular assessment and management,” she wrote, adding it is important to raise awareness among ob.gyns. and to improve cardiologists’ recognition of women at risk when they present for care for the first time.

These referrals should be made in the antepartum and early postpartum period, she said in an interview. More attention also must be paid to racial and ethnic disparities, and the role of cardiologists in addressing these disparities.

The CDC has emphasized racial and ethnic disparities in maternal mortality, noting in a 2019 Morbidity and Mortality Weekly report that, compared with white women, black and American Indian/Alaskan Native women aged over 30 years have a 300%-400% higher rate of pregnancy-related deaths (Morb Mortal Wkly Rep. 2019 Sep 6;68[35]:762-5).

With regard to disparities, Dr. Bullock-Palmer said the causes are multifold and may be related to a higher prevalence of CVD risk factors like obesity and hypertension in non-Hispanic black women.

“There may also be limited access to adequate postpartum care in this patient population,” she wrote, adding that some attention has been paid to addressing disparities, but that “there is a lot of work left to be done in resolving these inequities in maternal health care.”

Partnerships across specialties will help in addressing most of the factors associated with CVD and maternal death, she said.

The urgent need for these partnerships is underscored by the latest findings on CVD-related complications in pregnancy. A study published in March 2020 in the Journal of the American College of Cardiology, for example, looked specifically at the incidence of serious cardiac events (SCEs) in pregnant women with heart disease, and whether the events were preventable.

In a prospective cohort of 1,315 pregnancies among women with heart disease, Birgit Pfaller, MD, of the University of Toronto Pregnancy and Heart Disease Research Program, and colleagues found that SCEs occurred in 3.6% of cases (47 women) – most often during the antepartum period – that 49% were preventable, and that 74% were related to provider management factors.

The most common SCEs were cardiac death or arrest, heart failure, arrhythmias, and urgent intervention, and they were more likely to occur in women with acquired heart disease, severe aortic or mitral stenosis, mechanical valves, and systemic ventricular dysfunction. Adverse fetal and neonatal outcomes more than doubled in cases involving SCEs, compared with those without (62% vs. 29%), and adverse obstetric events occurred most often in women with severe preeclampsia.

“The majority of the preventable events occurred due to provider management factors, including: failure to identify the patient condition prior to pregnancy, failure to identify the patient as high risk, late recognition in cardiac deterioration, delay in treatment/intervention, inappropriate treatment, and lack of preconception counseling,” Melinda Davis, MD, of the University of Michigan, Ann Arbor, wrote in a summary and editorial published in the Journal of the American College of Cardiology.

Some preventable events were attributable to patient failure to seek care, noncompliance with care recommendations, and lack of access to care, Dr. Davis noted.

“These findings suggest that provider training, patient education, and health care advocacy are all important interventions to improve outcomes among pregnant women,” she wrote, adding that “the development of multidisciplinary cardio-obstetric clinics at tertiary care centers may also be helpful.”

Dr. Bullock-Palmer added the need for greater risk-prediction tools to the list, explaining that these are needed to assess CVD risk in the prenatal, antenatal, and postnatal period.

“The recently concluded Cardiac Disease in Pregnancy [CARPREG II] study indicated that there were 10 predictors that could be utilized to asses maternal CVD risk,” she noted.

The CARPREG II authors identified five general predictors (prior cardiac events or arrhythmias, poor functional class or cyanosis, high-risk valve disease/left ventricular outflow tract obstruction, systemic ventricular dysfunction, no prior cardiac interventions), four lesion-specific predictors (mechanical valves, high-risk aortopathies, pulmonary hypertension, coronary artery disease), and one delivery-of-care predictor (late pregnancy assessment), and incorporated them into a risk index.

“It is hopeful that these new initiatives will assist providers in improving their ability to appropriately risk stratify women,” Dr. Bullock-Palmer said.

 

Ongoing efforts

Efforts also are ongoing to develop the types of cardio-obstetric clinics mentioned by Dr. Davis and to establish collaborations and “pregnancy heart teams” as attention is increasingly focused on the U.S. maternal mortality crisis.

In fact, such teams are a cornerstone of ACOG’s guidance on pregnancy and heart disease. In May 2019 the college released a Practice Bulletin with 27 specific recommendations and conclusions relating to screening, diagnosis, and management of CVD for women during the prepregnancy period through the postpartum period.

Pregnant women and postpartum women with known or suspected CVD should undergo evaluation by a “pregnancy heart team that includes a cardiologist and maternal-fetal medicine subspecialist, or both, and other subspecialists as necessary,” according to the bulletin.

In a recent interview, Lisa Hollier, MD, immediate past president of ACOG and an instrumental figure in the push to better address maternal mortality – and in particular the cardiovascular contributors to the crisis – said she is “seeing a strengthening of that” with numerous organizations establishing pregnancy health teams.

Dr. Bullock-Palmer said she also is seeing progress, and added that collaboration should be prioritized even in the absence of dedicated pregnancy heart teams and clinics.

“Heart disease in pregnancy requires a multidisciplinary approach. You can’t just see the patient from the cardiac perspective – you also have to interact and team up with the obstetrician who is handling the pregnancy,” she said, adding that, without a dedicated team, coordination takes more effort, but is imperative for improving outcomes. “You have to collaborate at times when it is beyond the expertise of the institution or the physician; you have to know when to refer these higher-risk patients, particularly women with adult congenital heart disease.”

This referral should occur early – preferably in the antenatal period, she added.

The most important thing, however, is “recognizing these women ... even before the pregnancy,” Dr. Bullock-Palmer said, explaining that this can facilitate the necessary management – and in some cases, postponement – of pregnancy for women whose cardiac issues need to be addressed first.

Among other efforts to address maternal mortality are several programs developed by ACOG, and the Heart Outcomes in Pregnancy: Expectations for Mom and Baby Registry (HOPE) project of the Saint Luke’s Health System in Kansas.

“Hopefully the [HOPE] research collaborative ... which aims to address key clinical questions surrounding the preconception period, antenatal care, delivery planning and outcomes, and long-term postpartum care and outcomes of women will help to address the knowledge gaps and disparities in the care of women with heart disease in pregnancy,” Dr. Bullock-Palmer wrote in her article.

CVD-related risks in the post partum

Dr. Bullock-Palmer has particular concern for postpartum follow-up, given the increased risk for future heart disease among women with CVD-related pregnancy complications and the heightened risk of certain CVD-related events in the postpartum period.

That’s a component of the crisis that also was addressed during a press briefing at the 2019 ACOG annual meeting when the Pregnancy and Heart Disease Practice Bulletin was released.

Sharon Worcester/MDedge News

James Martin, MD, chair of ACOG’s Pregnancy and Heart Disease Task Force and a past ACOG president, explained during the briefing that CVD-related risks may accelerate and persist in the days and weeks after delivery, underscoring the need for follow-up and postpartum care.

Cardiomyopathy is a particular concern during this time – it’s the major cause of maternal mortality after 42 days, he noted. An emphasis on postpartum care also is especially important given that some data suggest up to 40% of women don’t return for that care.

“That is a very sad statistic and perhaps it reflects on our need to change payment models so that physicians and patients realize the importance of coming back for continuing care, because this really may be the end of pregnancy, but it is the beginning of the rest of their life,” he said. “And if they have cardiovascular disease or the risk factors ... they are going to possibly become worse over the course of their lifetime.”

[email protected]

Nearly 700 women died from pregnancy-related complications in the United States in 2018, and almost a third of those deaths were associated with cardiovascular disease, according to the latest data from the Centers for Disease Control and Prevention.

Strikingly, studies suggest that up to half of cardiovascular disease–related maternal deaths are preventable, yet CVD remains the leading cause of maternal morbidity and mortality – and the incidence has been rising steadily for 2 decades.

The American College of Obstetricians and Gynecologists says that acquired heart disease is the likely culprit in the rise in incidence of maternal mortality as women enter pregnancy with an increasingly heavy burden of CVD risk factors, including older age, obesity, diabetes, and hypertension.

“They are entering pregnancy while already at risk, and that has led to an increase in morbidity and mortality during pregnancy,” Renee Patrice Bullock-Palmer, MD, a cardiologist and director of the Women’s Heart Center at Deborah Heart and Lung Center in Browns Mills, N.J., explained in an interview. “Unfortunately, among developed countries, the U.S. has the highest rates of maternal morbidity and mortality, and that’s shocking.”

It’s a problem that requires collaboration between obstetricians, cardiologists, and others involved in the care of pregnant women, she said.
 

The data and the depth of the crisis

The maternal mortality rate in 1987 – the year the CDC’s Pregnancy Mortality Surveillance System was implemented – was 7.2 per 100,000 live births. The rate in 2016 was more than double that at 16.9, and the rate in 2018, the most recent year for which data are available, was 17.4 – and significant racial and ethnic disparities in those rates have persisted over time.

In an August 2019 article published on the American Heart Association website, Dr. Bullock-Palmer addressed the cardiovascular state of health for pregnant women and the role of the cardiologists in their care, noting that there is a “role for increased collaboration between the cardiologist and the obstetrician with regards to a pregnancy heart team.”

“It is vital that mothers who are at increased risk for CVD or have established CVD be referred to a cardiologist for cardiovascular assessment and management,” she wrote, adding it is important to raise awareness among ob.gyns. and to improve cardiologists’ recognition of women at risk when they present for care for the first time.

These referrals should be made in the antepartum and early postpartum period, she said in an interview. More attention also must be paid to racial and ethnic disparities, and the role of cardiologists in addressing these disparities.

The CDC has emphasized racial and ethnic disparities in maternal mortality, noting in a 2019 Morbidity and Mortality Weekly report that, compared with white women, black and American Indian/Alaskan Native women aged over 30 years have a 300%-400% higher rate of pregnancy-related deaths (Morb Mortal Wkly Rep. 2019 Sep 6;68[35]:762-5).

With regard to disparities, Dr. Bullock-Palmer said the causes are multifold and may be related to a higher prevalence of CVD risk factors like obesity and hypertension in non-Hispanic black women.

“There may also be limited access to adequate postpartum care in this patient population,” she wrote, adding that some attention has been paid to addressing disparities, but that “there is a lot of work left to be done in resolving these inequities in maternal health care.”

Partnerships across specialties will help in addressing most of the factors associated with CVD and maternal death, she said.

The urgent need for these partnerships is underscored by the latest findings on CVD-related complications in pregnancy. A study published in March 2020 in the Journal of the American College of Cardiology, for example, looked specifically at the incidence of serious cardiac events (SCEs) in pregnant women with heart disease, and whether the events were preventable.

In a prospective cohort of 1,315 pregnancies among women with heart disease, Birgit Pfaller, MD, of the University of Toronto Pregnancy and Heart Disease Research Program, and colleagues found that SCEs occurred in 3.6% of cases (47 women) – most often during the antepartum period – that 49% were preventable, and that 74% were related to provider management factors.

The most common SCEs were cardiac death or arrest, heart failure, arrhythmias, and urgent intervention, and they were more likely to occur in women with acquired heart disease, severe aortic or mitral stenosis, mechanical valves, and systemic ventricular dysfunction. Adverse fetal and neonatal outcomes more than doubled in cases involving SCEs, compared with those without (62% vs. 29%), and adverse obstetric events occurred most often in women with severe preeclampsia.

“The majority of the preventable events occurred due to provider management factors, including: failure to identify the patient condition prior to pregnancy, failure to identify the patient as high risk, late recognition in cardiac deterioration, delay in treatment/intervention, inappropriate treatment, and lack of preconception counseling,” Melinda Davis, MD, of the University of Michigan, Ann Arbor, wrote in a summary and editorial published in the Journal of the American College of Cardiology.

Some preventable events were attributable to patient failure to seek care, noncompliance with care recommendations, and lack of access to care, Dr. Davis noted.

“These findings suggest that provider training, patient education, and health care advocacy are all important interventions to improve outcomes among pregnant women,” she wrote, adding that “the development of multidisciplinary cardio-obstetric clinics at tertiary care centers may also be helpful.”

Dr. Bullock-Palmer added the need for greater risk-prediction tools to the list, explaining that these are needed to assess CVD risk in the prenatal, antenatal, and postnatal period.

“The recently concluded Cardiac Disease in Pregnancy [CARPREG II] study indicated that there were 10 predictors that could be utilized to asses maternal CVD risk,” she noted.

The CARPREG II authors identified five general predictors (prior cardiac events or arrhythmias, poor functional class or cyanosis, high-risk valve disease/left ventricular outflow tract obstruction, systemic ventricular dysfunction, no prior cardiac interventions), four lesion-specific predictors (mechanical valves, high-risk aortopathies, pulmonary hypertension, coronary artery disease), and one delivery-of-care predictor (late pregnancy assessment), and incorporated them into a risk index.

“It is hopeful that these new initiatives will assist providers in improving their ability to appropriately risk stratify women,” Dr. Bullock-Palmer said.

 

Ongoing efforts

Efforts also are ongoing to develop the types of cardio-obstetric clinics mentioned by Dr. Davis and to establish collaborations and “pregnancy heart teams” as attention is increasingly focused on the U.S. maternal mortality crisis.

In fact, such teams are a cornerstone of ACOG’s guidance on pregnancy and heart disease. In May 2019 the college released a Practice Bulletin with 27 specific recommendations and conclusions relating to screening, diagnosis, and management of CVD for women during the prepregnancy period through the postpartum period.

Pregnant women and postpartum women with known or suspected CVD should undergo evaluation by a “pregnancy heart team that includes a cardiologist and maternal-fetal medicine subspecialist, or both, and other subspecialists as necessary,” according to the bulletin.

In a recent interview, Lisa Hollier, MD, immediate past president of ACOG and an instrumental figure in the push to better address maternal mortality – and in particular the cardiovascular contributors to the crisis – said she is “seeing a strengthening of that” with numerous organizations establishing pregnancy health teams.

Dr. Bullock-Palmer said she also is seeing progress, and added that collaboration should be prioritized even in the absence of dedicated pregnancy heart teams and clinics.

“Heart disease in pregnancy requires a multidisciplinary approach. You can’t just see the patient from the cardiac perspective – you also have to interact and team up with the obstetrician who is handling the pregnancy,” she said, adding that, without a dedicated team, coordination takes more effort, but is imperative for improving outcomes. “You have to collaborate at times when it is beyond the expertise of the institution or the physician; you have to know when to refer these higher-risk patients, particularly women with adult congenital heart disease.”

This referral should occur early – preferably in the antenatal period, she added.

The most important thing, however, is “recognizing these women ... even before the pregnancy,” Dr. Bullock-Palmer said, explaining that this can facilitate the necessary management – and in some cases, postponement – of pregnancy for women whose cardiac issues need to be addressed first.

Among other efforts to address maternal mortality are several programs developed by ACOG, and the Heart Outcomes in Pregnancy: Expectations for Mom and Baby Registry (HOPE) project of the Saint Luke’s Health System in Kansas.

“Hopefully the [HOPE] research collaborative ... which aims to address key clinical questions surrounding the preconception period, antenatal care, delivery planning and outcomes, and long-term postpartum care and outcomes of women will help to address the knowledge gaps and disparities in the care of women with heart disease in pregnancy,” Dr. Bullock-Palmer wrote in her article.

CVD-related risks in the post partum

Dr. Bullock-Palmer has particular concern for postpartum follow-up, given the increased risk for future heart disease among women with CVD-related pregnancy complications and the heightened risk of certain CVD-related events in the postpartum period.

That’s a component of the crisis that also was addressed during a press briefing at the 2019 ACOG annual meeting when the Pregnancy and Heart Disease Practice Bulletin was released.

Sharon Worcester/MDedge News

James Martin, MD, chair of ACOG’s Pregnancy and Heart Disease Task Force and a past ACOG president, explained during the briefing that CVD-related risks may accelerate and persist in the days and weeks after delivery, underscoring the need for follow-up and postpartum care.

Cardiomyopathy is a particular concern during this time – it’s the major cause of maternal mortality after 42 days, he noted. An emphasis on postpartum care also is especially important given that some data suggest up to 40% of women don’t return for that care.

“That is a very sad statistic and perhaps it reflects on our need to change payment models so that physicians and patients realize the importance of coming back for continuing care, because this really may be the end of pregnancy, but it is the beginning of the rest of their life,” he said. “And if they have cardiovascular disease or the risk factors ... they are going to possibly become worse over the course of their lifetime.”

[email protected]

Nearly 700 women died from pregnancy-related complications in the United States in 2018, and almost a third of those deaths were associated with cardiovascular disease, according to the latest data from the Centers for Disease Control and Prevention.

Strikingly, studies suggest that up to half of cardiovascular disease–related maternal deaths are preventable, yet CVD remains the leading cause of maternal morbidity and mortality – and the incidence has been rising steadily for 2 decades.

The American College of Obstetricians and Gynecologists says that acquired heart disease is the likely culprit in the rise in incidence of maternal mortality as women enter pregnancy with an increasingly heavy burden of CVD risk factors, including older age, obesity, diabetes, and hypertension.

“They are entering pregnancy while already at risk, and that has led to an increase in morbidity and mortality during pregnancy,” Renee Patrice Bullock-Palmer, MD, a cardiologist and director of the Women’s Heart Center at Deborah Heart and Lung Center in Browns Mills, N.J., explained in an interview. “Unfortunately, among developed countries, the U.S. has the highest rates of maternal morbidity and mortality, and that’s shocking.”

It’s a problem that requires collaboration between obstetricians, cardiologists, and others involved in the care of pregnant women, she said.
 

The data and the depth of the crisis

The maternal mortality rate in 1987 – the year the CDC’s Pregnancy Mortality Surveillance System was implemented – was 7.2 per 100,000 live births. The rate in 2016 was more than double that at 16.9, and the rate in 2018, the most recent year for which data are available, was 17.4 – and significant racial and ethnic disparities in those rates have persisted over time.

In an August 2019 article published on the American Heart Association website, Dr. Bullock-Palmer addressed the cardiovascular state of health for pregnant women and the role of the cardiologists in their care, noting that there is a “role for increased collaboration between the cardiologist and the obstetrician with regards to a pregnancy heart team.”

“It is vital that mothers who are at increased risk for CVD or have established CVD be referred to a cardiologist for cardiovascular assessment and management,” she wrote, adding it is important to raise awareness among ob.gyns. and to improve cardiologists’ recognition of women at risk when they present for care for the first time.

These referrals should be made in the antepartum and early postpartum period, she said in an interview. More attention also must be paid to racial and ethnic disparities, and the role of cardiologists in addressing these disparities.

The CDC has emphasized racial and ethnic disparities in maternal mortality, noting in a 2019 Morbidity and Mortality Weekly report that, compared with white women, black and American Indian/Alaskan Native women aged over 30 years have a 300%-400% higher rate of pregnancy-related deaths (Morb Mortal Wkly Rep. 2019 Sep 6;68[35]:762-5).

With regard to disparities, Dr. Bullock-Palmer said the causes are multifold and may be related to a higher prevalence of CVD risk factors like obesity and hypertension in non-Hispanic black women.

“There may also be limited access to adequate postpartum care in this patient population,” she wrote, adding that some attention has been paid to addressing disparities, but that “there is a lot of work left to be done in resolving these inequities in maternal health care.”

Partnerships across specialties will help in addressing most of the factors associated with CVD and maternal death, she said.

The urgent need for these partnerships is underscored by the latest findings on CVD-related complications in pregnancy. A study published in March 2020 in the Journal of the American College of Cardiology, for example, looked specifically at the incidence of serious cardiac events (SCEs) in pregnant women with heart disease, and whether the events were preventable.

In a prospective cohort of 1,315 pregnancies among women with heart disease, Birgit Pfaller, MD, of the University of Toronto Pregnancy and Heart Disease Research Program, and colleagues found that SCEs occurred in 3.6% of cases (47 women) – most often during the antepartum period – that 49% were preventable, and that 74% were related to provider management factors.

The most common SCEs were cardiac death or arrest, heart failure, arrhythmias, and urgent intervention, and they were more likely to occur in women with acquired heart disease, severe aortic or mitral stenosis, mechanical valves, and systemic ventricular dysfunction. Adverse fetal and neonatal outcomes more than doubled in cases involving SCEs, compared with those without (62% vs. 29%), and adverse obstetric events occurred most often in women with severe preeclampsia.

“The majority of the preventable events occurred due to provider management factors, including: failure to identify the patient condition prior to pregnancy, failure to identify the patient as high risk, late recognition in cardiac deterioration, delay in treatment/intervention, inappropriate treatment, and lack of preconception counseling,” Melinda Davis, MD, of the University of Michigan, Ann Arbor, wrote in a summary and editorial published in the Journal of the American College of Cardiology.

Some preventable events were attributable to patient failure to seek care, noncompliance with care recommendations, and lack of access to care, Dr. Davis noted.

“These findings suggest that provider training, patient education, and health care advocacy are all important interventions to improve outcomes among pregnant women,” she wrote, adding that “the development of multidisciplinary cardio-obstetric clinics at tertiary care centers may also be helpful.”

Dr. Bullock-Palmer added the need for greater risk-prediction tools to the list, explaining that these are needed to assess CVD risk in the prenatal, antenatal, and postnatal period.

“The recently concluded Cardiac Disease in Pregnancy [CARPREG II] study indicated that there were 10 predictors that could be utilized to asses maternal CVD risk,” she noted.

The CARPREG II authors identified five general predictors (prior cardiac events or arrhythmias, poor functional class or cyanosis, high-risk valve disease/left ventricular outflow tract obstruction, systemic ventricular dysfunction, no prior cardiac interventions), four lesion-specific predictors (mechanical valves, high-risk aortopathies, pulmonary hypertension, coronary artery disease), and one delivery-of-care predictor (late pregnancy assessment), and incorporated them into a risk index.

“It is hopeful that these new initiatives will assist providers in improving their ability to appropriately risk stratify women,” Dr. Bullock-Palmer said.

 

Ongoing efforts

Efforts also are ongoing to develop the types of cardio-obstetric clinics mentioned by Dr. Davis and to establish collaborations and “pregnancy heart teams” as attention is increasingly focused on the U.S. maternal mortality crisis.

In fact, such teams are a cornerstone of ACOG’s guidance on pregnancy and heart disease. In May 2019 the college released a Practice Bulletin with 27 specific recommendations and conclusions relating to screening, diagnosis, and management of CVD for women during the prepregnancy period through the postpartum period.

Pregnant women and postpartum women with known or suspected CVD should undergo evaluation by a “pregnancy heart team that includes a cardiologist and maternal-fetal medicine subspecialist, or both, and other subspecialists as necessary,” according to the bulletin.

In a recent interview, Lisa Hollier, MD, immediate past president of ACOG and an instrumental figure in the push to better address maternal mortality – and in particular the cardiovascular contributors to the crisis – said she is “seeing a strengthening of that” with numerous organizations establishing pregnancy health teams.

Dr. Bullock-Palmer said she also is seeing progress, and added that collaboration should be prioritized even in the absence of dedicated pregnancy heart teams and clinics.

“Heart disease in pregnancy requires a multidisciplinary approach. You can’t just see the patient from the cardiac perspective – you also have to interact and team up with the obstetrician who is handling the pregnancy,” she said, adding that, without a dedicated team, coordination takes more effort, but is imperative for improving outcomes. “You have to collaborate at times when it is beyond the expertise of the institution or the physician; you have to know when to refer these higher-risk patients, particularly women with adult congenital heart disease.”

This referral should occur early – preferably in the antenatal period, she added.

The most important thing, however, is “recognizing these women ... even before the pregnancy,” Dr. Bullock-Palmer said, explaining that this can facilitate the necessary management – and in some cases, postponement – of pregnancy for women whose cardiac issues need to be addressed first.

Among other efforts to address maternal mortality are several programs developed by ACOG, and the Heart Outcomes in Pregnancy: Expectations for Mom and Baby Registry (HOPE) project of the Saint Luke’s Health System in Kansas.

“Hopefully the [HOPE] research collaborative ... which aims to address key clinical questions surrounding the preconception period, antenatal care, delivery planning and outcomes, and long-term postpartum care and outcomes of women will help to address the knowledge gaps and disparities in the care of women with heart disease in pregnancy,” Dr. Bullock-Palmer wrote in her article.

CVD-related risks in the post partum

Dr. Bullock-Palmer has particular concern for postpartum follow-up, given the increased risk for future heart disease among women with CVD-related pregnancy complications and the heightened risk of certain CVD-related events in the postpartum period.

That’s a component of the crisis that also was addressed during a press briefing at the 2019 ACOG annual meeting when the Pregnancy and Heart Disease Practice Bulletin was released.

Sharon Worcester/MDedge News

James Martin, MD, chair of ACOG’s Pregnancy and Heart Disease Task Force and a past ACOG president, explained during the briefing that CVD-related risks may accelerate and persist in the days and weeks after delivery, underscoring the need for follow-up and postpartum care.

Cardiomyopathy is a particular concern during this time – it’s the major cause of maternal mortality after 42 days, he noted. An emphasis on postpartum care also is especially important given that some data suggest up to 40% of women don’t return for that care.

“That is a very sad statistic and perhaps it reflects on our need to change payment models so that physicians and patients realize the importance of coming back for continuing care, because this really may be the end of pregnancy, but it is the beginning of the rest of their life,” he said. “And if they have cardiovascular disease or the risk factors ... they are going to possibly become worse over the course of their lifetime.”

[email protected]

Adding trastuzumab to carboplatin/paclitaxel improved survival in patients with advanced or recurrent HER2/Neu-positive uterine serous carcinoma (USC), according to an updated analysis from a phase 2 trial.

Dr Amanda Nickles Fader

At a median follow-up of 25.9 months, the median progression-free survival (PFS) was 12.9 months in patients who received trastuzumab plus carboplatin/paclitaxel and 8.0 months in patients who received only carboplatin/paclitaxel. The median overall survival (OS) was 29.6 months and 24.4 months, respectively.

Amanda Nickles Fader, MD, of Johns Hopkins Medicine, Baltimore, and colleagues reported these findings in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
 

Confirmed benefit

The phase 2 trial was designed to assess whether trastuzumab, a humanized monoclonal antibody that targets HER2/neu – a growth factor receptor found in almost all USC cases and overexpressed in 30% of cases – would improve survival in patients with USC, Dr. Nickles Fader explained in an interview. She noted that trastuzumab has been shown to provide benefit in breast cancer patients with HER2/neu overexpression.

“[U]terine serous carcinoma ... is a very aggressive high-grade endometrial cancer subtype that is associated with really poor clinical outcomes and significant mortality,” Dr. Nickles Fader said. “It represents fewer than 10% of all uterine cancer cases, but it actually accounts for a disproportionate 40% of all deaths from uterine cancer.”

The overall survival among USC patients is about 45%, compared with 91% for more common lower-grade types of uterine cancers, she added.

“The conventional treatments for uterine serous carcinoma include surgery and then chemotherapy, but we’ve only really gotten so far by using a sort of one-size-fits-all treatment philosophy,” Dr. Nickles Fader said.

Based on preliminary findings from the current trial (J Clin Oncol. 2018 Jul 10;36[20]:2044-51), trastuzumab plus carboplatin/paclitaxel is now recognized as an alternative standard in treating advanced or recurrent HER2/Neu-positive USC, and this updated analysis confirms the benefits of adding trastuzumab, she said.
 

PFS, OS, and toxicity

There were 58 evaluable patients with primary stage III-IV or recurrent USC who were randomized to receive six cycles of carboplatin/paclitaxel alone or in combination with intravenous trastuzumab given until toxicity or progression.

The median PFS at a median follow-up of 25.9 months “very significantly favored” the trastuzumab arm, Dr. Nickles Fader said. The median PFS was 12.9 months in the trastuzumab arm and 8.0 months in the carboplatin/paclitaxel arm (hazard ratio, 0.46; P = .005).

In the 41 patients undergoing primary treatment, the median PFS was 17.7 months in the trastuzumab arm and 9.3 months in the control arm (HR, 0.44; P = .015). In the 17 patients with recurrent disease, the median PFS was 9.2 months and 7.0 months, respectively (HR, 0.12; P = .004).

“We were very pleased to see that there was also an overall survival benefit of about 5 months in the trastuzumab arm, compared to the control arm,” Dr. Nickles Fader said. The median OS was 29.6 months and 24.4 months, respectively (HR, 0.58; P = .046).

The PFS and OS benefit was “particularly striking” in the stage III-IV patients, according to Dr. Nickles Fader and colleagues. In this subgroup, the median OS was not reached in the trastuzumab arm, and it was 25.4 months in the control arm (HR, 0.49; P = .041).

Long-term toxicity did not differ between the treatment arms.
 

Applications and next steps

“The take-home message here is women should be tested if they have this subtype,” Dr. Nickles Fader said. “If they’re newly diagnosed, they should be tested for the HER2/neu receptor, and if [it is overexpressed] and they have advanced disease, we do recommend treatment with not only the conventional treatment, but with trastuzumab added to that, because that’s where we saw the most benefit.”

This is the only trial that has ever shown a major PFS and OS difference with combination targeted therapy and conventional chemotherapy in USC, Dr. Nickles Fader noted.

“So it was really exciting to see that,” she said, adding that a “much larger cooperative group trial” is being designed by the National Cancer Institute and NRG Oncology Group to look at this approach in HER2-positive, advanced-stage uterine cancers. The trial will include patients with USC, but it will extend to other uterine cancer types as well.

“We’re looking at different combinations of anti-HER2 therapies to sort of validate the results of this trial, but also to study this in other tumors that are HER2 positive,” Dr. Nickles Fader explained.

She also stressed the importance of addressing racial disparities in survival among women with USC, as African American women have higher rates of USC and related mortality than do other groups.

“It’s going to be important to look at not only molecular targets and improving survival but also racial inequalities and potentially epigenetics to really improve survival across the board,” Dr. Nickles Fader said.

She reported having no disclosures. The trial was sponsored by Yale University in collaboration with Genentech.

[email protected]

SOURCE: Nickles Fader A et al. SGO 2020, Abstract 12.

Adding trastuzumab to carboplatin/paclitaxel improved survival in patients with advanced or recurrent HER2/Neu-positive uterine serous carcinoma (USC), according to an updated analysis from a phase 2 trial.

Dr Amanda Nickles Fader

At a median follow-up of 25.9 months, the median progression-free survival (PFS) was 12.9 months in patients who received trastuzumab plus carboplatin/paclitaxel and 8.0 months in patients who received only carboplatin/paclitaxel. The median overall survival (OS) was 29.6 months and 24.4 months, respectively.

Amanda Nickles Fader, MD, of Johns Hopkins Medicine, Baltimore, and colleagues reported these findings in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
 

Confirmed benefit

The phase 2 trial was designed to assess whether trastuzumab, a humanized monoclonal antibody that targets HER2/neu – a growth factor receptor found in almost all USC cases and overexpressed in 30% of cases – would improve survival in patients with USC, Dr. Nickles Fader explained in an interview. She noted that trastuzumab has been shown to provide benefit in breast cancer patients with HER2/neu overexpression.

“[U]terine serous carcinoma ... is a very aggressive high-grade endometrial cancer subtype that is associated with really poor clinical outcomes and significant mortality,” Dr. Nickles Fader said. “It represents fewer than 10% of all uterine cancer cases, but it actually accounts for a disproportionate 40% of all deaths from uterine cancer.”

The overall survival among USC patients is about 45%, compared with 91% for more common lower-grade types of uterine cancers, she added.

“The conventional treatments for uterine serous carcinoma include surgery and then chemotherapy, but we’ve only really gotten so far by using a sort of one-size-fits-all treatment philosophy,” Dr. Nickles Fader said.

Based on preliminary findings from the current trial (J Clin Oncol. 2018 Jul 10;36[20]:2044-51), trastuzumab plus carboplatin/paclitaxel is now recognized as an alternative standard in treating advanced or recurrent HER2/Neu-positive USC, and this updated analysis confirms the benefits of adding trastuzumab, she said.
 

PFS, OS, and toxicity

There were 58 evaluable patients with primary stage III-IV or recurrent USC who were randomized to receive six cycles of carboplatin/paclitaxel alone or in combination with intravenous trastuzumab given until toxicity or progression.

The median PFS at a median follow-up of 25.9 months “very significantly favored” the trastuzumab arm, Dr. Nickles Fader said. The median PFS was 12.9 months in the trastuzumab arm and 8.0 months in the carboplatin/paclitaxel arm (hazard ratio, 0.46; P = .005).

In the 41 patients undergoing primary treatment, the median PFS was 17.7 months in the trastuzumab arm and 9.3 months in the control arm (HR, 0.44; P = .015). In the 17 patients with recurrent disease, the median PFS was 9.2 months and 7.0 months, respectively (HR, 0.12; P = .004).

“We were very pleased to see that there was also an overall survival benefit of about 5 months in the trastuzumab arm, compared to the control arm,” Dr. Nickles Fader said. The median OS was 29.6 months and 24.4 months, respectively (HR, 0.58; P = .046).

The PFS and OS benefit was “particularly striking” in the stage III-IV patients, according to Dr. Nickles Fader and colleagues. In this subgroup, the median OS was not reached in the trastuzumab arm, and it was 25.4 months in the control arm (HR, 0.49; P = .041).

Long-term toxicity did not differ between the treatment arms.
 

Applications and next steps

“The take-home message here is women should be tested if they have this subtype,” Dr. Nickles Fader said. “If they’re newly diagnosed, they should be tested for the HER2/neu receptor, and if [it is overexpressed] and they have advanced disease, we do recommend treatment with not only the conventional treatment, but with trastuzumab added to that, because that’s where we saw the most benefit.”

This is the only trial that has ever shown a major PFS and OS difference with combination targeted therapy and conventional chemotherapy in USC, Dr. Nickles Fader noted.

“So it was really exciting to see that,” she said, adding that a “much larger cooperative group trial” is being designed by the National Cancer Institute and NRG Oncology Group to look at this approach in HER2-positive, advanced-stage uterine cancers. The trial will include patients with USC, but it will extend to other uterine cancer types as well.

“We’re looking at different combinations of anti-HER2 therapies to sort of validate the results of this trial, but also to study this in other tumors that are HER2 positive,” Dr. Nickles Fader explained.

She also stressed the importance of addressing racial disparities in survival among women with USC, as African American women have higher rates of USC and related mortality than do other groups.

“It’s going to be important to look at not only molecular targets and improving survival but also racial inequalities and potentially epigenetics to really improve survival across the board,” Dr. Nickles Fader said.

She reported having no disclosures. The trial was sponsored by Yale University in collaboration with Genentech.

[email protected]

SOURCE: Nickles Fader A et al. SGO 2020, Abstract 12.

Adding trastuzumab to carboplatin/paclitaxel improved survival in patients with advanced or recurrent HER2/Neu-positive uterine serous carcinoma (USC), according to an updated analysis from a phase 2 trial.

Dr Amanda Nickles Fader

At a median follow-up of 25.9 months, the median progression-free survival (PFS) was 12.9 months in patients who received trastuzumab plus carboplatin/paclitaxel and 8.0 months in patients who received only carboplatin/paclitaxel. The median overall survival (OS) was 29.6 months and 24.4 months, respectively.

Amanda Nickles Fader, MD, of Johns Hopkins Medicine, Baltimore, and colleagues reported these findings in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
 

Confirmed benefit

The phase 2 trial was designed to assess whether trastuzumab, a humanized monoclonal antibody that targets HER2/neu – a growth factor receptor found in almost all USC cases and overexpressed in 30% of cases – would improve survival in patients with USC, Dr. Nickles Fader explained in an interview. She noted that trastuzumab has been shown to provide benefit in breast cancer patients with HER2/neu overexpression.

“[U]terine serous carcinoma ... is a very aggressive high-grade endometrial cancer subtype that is associated with really poor clinical outcomes and significant mortality,” Dr. Nickles Fader said. “It represents fewer than 10% of all uterine cancer cases, but it actually accounts for a disproportionate 40% of all deaths from uterine cancer.”

The overall survival among USC patients is about 45%, compared with 91% for more common lower-grade types of uterine cancers, she added.

“The conventional treatments for uterine serous carcinoma include surgery and then chemotherapy, but we’ve only really gotten so far by using a sort of one-size-fits-all treatment philosophy,” Dr. Nickles Fader said.

Based on preliminary findings from the current trial (J Clin Oncol. 2018 Jul 10;36[20]:2044-51), trastuzumab plus carboplatin/paclitaxel is now recognized as an alternative standard in treating advanced or recurrent HER2/Neu-positive USC, and this updated analysis confirms the benefits of adding trastuzumab, she said.
 

PFS, OS, and toxicity

There were 58 evaluable patients with primary stage III-IV or recurrent USC who were randomized to receive six cycles of carboplatin/paclitaxel alone or in combination with intravenous trastuzumab given until toxicity or progression.

The median PFS at a median follow-up of 25.9 months “very significantly favored” the trastuzumab arm, Dr. Nickles Fader said. The median PFS was 12.9 months in the trastuzumab arm and 8.0 months in the carboplatin/paclitaxel arm (hazard ratio, 0.46; P = .005).

In the 41 patients undergoing primary treatment, the median PFS was 17.7 months in the trastuzumab arm and 9.3 months in the control arm (HR, 0.44; P = .015). In the 17 patients with recurrent disease, the median PFS was 9.2 months and 7.0 months, respectively (HR, 0.12; P = .004).

“We were very pleased to see that there was also an overall survival benefit of about 5 months in the trastuzumab arm, compared to the control arm,” Dr. Nickles Fader said. The median OS was 29.6 months and 24.4 months, respectively (HR, 0.58; P = .046).

The PFS and OS benefit was “particularly striking” in the stage III-IV patients, according to Dr. Nickles Fader and colleagues. In this subgroup, the median OS was not reached in the trastuzumab arm, and it was 25.4 months in the control arm (HR, 0.49; P = .041).

Long-term toxicity did not differ between the treatment arms.
 

Applications and next steps

“The take-home message here is women should be tested if they have this subtype,” Dr. Nickles Fader said. “If they’re newly diagnosed, they should be tested for the HER2/neu receptor, and if [it is overexpressed] and they have advanced disease, we do recommend treatment with not only the conventional treatment, but with trastuzumab added to that, because that’s where we saw the most benefit.”

This is the only trial that has ever shown a major PFS and OS difference with combination targeted therapy and conventional chemotherapy in USC, Dr. Nickles Fader noted.

“So it was really exciting to see that,” she said, adding that a “much larger cooperative group trial” is being designed by the National Cancer Institute and NRG Oncology Group to look at this approach in HER2-positive, advanced-stage uterine cancers. The trial will include patients with USC, but it will extend to other uterine cancer types as well.

“We’re looking at different combinations of anti-HER2 therapies to sort of validate the results of this trial, but also to study this in other tumors that are HER2 positive,” Dr. Nickles Fader explained.

She also stressed the importance of addressing racial disparities in survival among women with USC, as African American women have higher rates of USC and related mortality than do other groups.

“It’s going to be important to look at not only molecular targets and improving survival but also racial inequalities and potentially epigenetics to really improve survival across the board,” Dr. Nickles Fader said.

She reported having no disclosures. The trial was sponsored by Yale University in collaboration with Genentech.

[email protected]

SOURCE: Nickles Fader A et al. SGO 2020, Abstract 12.

A significant compensation discrepancy exists between male and female gynecologic oncologists, a recent survey suggests.

Dr. Katherine M. Croft

After controlling for differences between the genders, the male gynecologic oncologists surveyed were 1.28 times more likely than their female counterparts to earn a salary above the median, according to Katherine M. Croft, MD, of the University of Virginia, Charlottesville.

Dr. Croft and colleagues reported findings from the survey in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

Of 263 members of the Society of Gynecologic Oncology who responded to the anonymous survey, 41% were women and 59% were men. The median annual salaries were $380,000 and $500,000 respectively.

“Comparing compensation by gender, there was a $120,000 difference in median salary when you compare them on a surface level,” Dr. Croft said. “Combing through the data further, we found that there were few other differences by gender.”

There were no differences between genders with respect to group size, percentage of protected research time, frequency of call, or geographic location. However, men were more likely to be compensated for extra call and were more likely to respond to obstetrical emergencies, and those differences were statistically significant.

Further, female gynecologic oncologists were younger and had been in practice for fewer years. They also were more likely to work in an academic setting and to work with residents.

“For men, the odds of making above the median salary was 1.28 times that of female providers when controlling for these differences” Dr. Croft said.

Significant compensation differences were noted based on practice setting. When these were substratified by gender, only academic or teaching hospitals and teaching hospital/community hybrids had significant pay differences by gender.

Academic or teaching hospitals comprised the largest subgroup, allowing for further analysis.

“Age and years post fellowship were the only significant differences by gender in this group,” Dr. Croft said. “Again, female providers earned less than their male counterparts, with mean compensation of $349,717, compared with $461,054.”

In fact, less than 25% of women in academic practice in this survey made above the median reported salary, Dr. Croft noted. Controlling not only for differences between male and female providers in this group but also for other known factors affecting compensation, the odds of a male provider making greater than the median salary were 1.77 times that of female providers.

Women represent nearly a third of all practicing physicians, but their salaries continue to lag behind those of men, Dr. Croft noted. She added that “this is the first study that has been presented with regards to gynecologic oncology gender salary discrepancies.”

The findings are limited by survey response bias and a potential lack of data that could explain some of the discrepancies. The study was originally designed to look at on-call compensation, so respondents were not queried about academic ranking or specific work responsibilities. Still, Dr. Croft said the findings point to a need for policy reform to ensure equitable compensation.

“My hope is that these data open a dialogue to further explore discrepancies by gender in our field,” she said.

Dr. Croft reported having no disclosures.

[email protected]

SOURCE: Croft K et al. SGO 2020, Abstract 15.

A significant compensation discrepancy exists between male and female gynecologic oncologists, a recent survey suggests.

Dr. Katherine M. Croft

After controlling for differences between the genders, the male gynecologic oncologists surveyed were 1.28 times more likely than their female counterparts to earn a salary above the median, according to Katherine M. Croft, MD, of the University of Virginia, Charlottesville.

Dr. Croft and colleagues reported findings from the survey in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

Of 263 members of the Society of Gynecologic Oncology who responded to the anonymous survey, 41% were women and 59% were men. The median annual salaries were $380,000 and $500,000 respectively.

“Comparing compensation by gender, there was a $120,000 difference in median salary when you compare them on a surface level,” Dr. Croft said. “Combing through the data further, we found that there were few other differences by gender.”

There were no differences between genders with respect to group size, percentage of protected research time, frequency of call, or geographic location. However, men were more likely to be compensated for extra call and were more likely to respond to obstetrical emergencies, and those differences were statistically significant.

Further, female gynecologic oncologists were younger and had been in practice for fewer years. They also were more likely to work in an academic setting and to work with residents.

“For men, the odds of making above the median salary was 1.28 times that of female providers when controlling for these differences” Dr. Croft said.

Significant compensation differences were noted based on practice setting. When these were substratified by gender, only academic or teaching hospitals and teaching hospital/community hybrids had significant pay differences by gender.

Academic or teaching hospitals comprised the largest subgroup, allowing for further analysis.

“Age and years post fellowship were the only significant differences by gender in this group,” Dr. Croft said. “Again, female providers earned less than their male counterparts, with mean compensation of $349,717, compared with $461,054.”

In fact, less than 25% of women in academic practice in this survey made above the median reported salary, Dr. Croft noted. Controlling not only for differences between male and female providers in this group but also for other known factors affecting compensation, the odds of a male provider making greater than the median salary were 1.77 times that of female providers.

Women represent nearly a third of all practicing physicians, but their salaries continue to lag behind those of men, Dr. Croft noted. She added that “this is the first study that has been presented with regards to gynecologic oncology gender salary discrepancies.”

The findings are limited by survey response bias and a potential lack of data that could explain some of the discrepancies. The study was originally designed to look at on-call compensation, so respondents were not queried about academic ranking or specific work responsibilities. Still, Dr. Croft said the findings point to a need for policy reform to ensure equitable compensation.

“My hope is that these data open a dialogue to further explore discrepancies by gender in our field,” she said.

Dr. Croft reported having no disclosures.

[email protected]

SOURCE: Croft K et al. SGO 2020, Abstract 15.

A significant compensation discrepancy exists between male and female gynecologic oncologists, a recent survey suggests.

Dr. Katherine M. Croft

After controlling for differences between the genders, the male gynecologic oncologists surveyed were 1.28 times more likely than their female counterparts to earn a salary above the median, according to Katherine M. Croft, MD, of the University of Virginia, Charlottesville.

Dr. Croft and colleagues reported findings from the survey in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.

Of 263 members of the Society of Gynecologic Oncology who responded to the anonymous survey, 41% were women and 59% were men. The median annual salaries were $380,000 and $500,000 respectively.

“Comparing compensation by gender, there was a $120,000 difference in median salary when you compare them on a surface level,” Dr. Croft said. “Combing through the data further, we found that there were few other differences by gender.”

There were no differences between genders with respect to group size, percentage of protected research time, frequency of call, or geographic location. However, men were more likely to be compensated for extra call and were more likely to respond to obstetrical emergencies, and those differences were statistically significant.

Further, female gynecologic oncologists were younger and had been in practice for fewer years. They also were more likely to work in an academic setting and to work with residents.

“For men, the odds of making above the median salary was 1.28 times that of female providers when controlling for these differences” Dr. Croft said.

Significant compensation differences were noted based on practice setting. When these were substratified by gender, only academic or teaching hospitals and teaching hospital/community hybrids had significant pay differences by gender.

Academic or teaching hospitals comprised the largest subgroup, allowing for further analysis.

“Age and years post fellowship were the only significant differences by gender in this group,” Dr. Croft said. “Again, female providers earned less than their male counterparts, with mean compensation of $349,717, compared with $461,054.”

In fact, less than 25% of women in academic practice in this survey made above the median reported salary, Dr. Croft noted. Controlling not only for differences between male and female providers in this group but also for other known factors affecting compensation, the odds of a male provider making greater than the median salary were 1.77 times that of female providers.

Women represent nearly a third of all practicing physicians, but their salaries continue to lag behind those of men, Dr. Croft noted. She added that “this is the first study that has been presented with regards to gynecologic oncology gender salary discrepancies.”

The findings are limited by survey response bias and a potential lack of data that could explain some of the discrepancies. The study was originally designed to look at on-call compensation, so respondents were not queried about academic ranking or specific work responsibilities. Still, Dr. Croft said the findings point to a need for policy reform to ensure equitable compensation.

“My hope is that these data open a dialogue to further explore discrepancies by gender in our field,” she said.

Dr. Croft reported having no disclosures.

[email protected]

SOURCE: Croft K et al. SGO 2020, Abstract 15.

Patients with type 2 diabetes who take metformin may have lower risk-adjusted mortality and readmission rates after surgery than do those who don’t take metformin, findings from a large retrospective cohort study suggest.

Of 10,088 individuals with diabetes who underwent a major surgery requiring hospital admission between January 1, 2010, and January 1, 2016, a total of 5,962 (59%) had received a prescription for metformin in the 180 days before surgery, and 5,460 of those patients were propensity score–matched to controls who did not receive a metformin prescription.

The study participants had a mean age of 67.7 years and underwent surgery requiring general anesthesia and postoperative admission at any of 15 hospitals in a single Pennsylvania health system. In addition to being prescribed metformin within 180 days before surgery, they also had metformin on their list of active medications at their most recent preoperative encounter before the surgery. The were followed until December 18, 2018.

In all, the 90-day and 5-year mortality hazards were reduced by 28% and 26%, respectively, in the metformin prescription recipients, compared with the propensity score–matched controls (hazard ratios, 0.72 and 0.74, respectively), Katherine M. Reitz, MD, and colleagues at the University of Pittsburgh reported in JAMA Surgery.

The readmission hazard – with mortality as a competing risk – was reduced by 16% at 30 days and 14% at 90 days (sub-HRs, 0.84 and 0.86, respectively), the researchers found.

“Hospital readmissions among those with preoperative metformin prescriptions were observed by postdischarge days 30 and 90 (304 [11%] and 538 [20.1%], respectively), whereas among those without prescriptions, 361 readmissions (13%) occurred by day 30 and 614 (23%) by day 90,” they wrote.

The investigators also noted that inflammation was reduced in patients who received a metformin prescription, compared with those who did not (mean preoperative neutrophil to leukocyte ratio, 4.5 vs. 5.0, respectively).

“In the full cohort, multivariable regression analysis similarly demonstrated that metformin was associated with a reduced hazard for both 90-day and 5-year mortality (adjusted HRs, 0.77 and 0.80, respectively) and for 30-day and 90-day readmission (aHR, 0.83 and 0.86), with mortality as a competing risk,” they added.

The findings support those from previous studies showing a decrease in all-cause mortality among diabetes patients taking metformin, said the researchers, noting that those patients had fewer age-related chronic diseases.

“These associations may reflect the anti-aging properties of metformin against the onset of disease or diabetes-associated complications. This study extends these finding by demonstrating that preoperative metformin prescriptions were associated with a reduction in postoperative mortality and readmission, a surrogate for postoperative complications, and with long-term mortality,” they wrote.

The study was limited by a number of factors, such as the potential for residual confounding inherent in retrospective analyses and a lack of adequate power to evaluate the association between metformin use and outcomes for individual surgical procedures. But the authors added that the findings are of note, because adults with comorbidities, such as diabetes, have less physiological reserve and an increased postoperative mortality and readmission rate. The results, therefore, warrant investigation with a prospective randomized clinical trial, they concluded.

In an accompanying editorial, Elizabeth L. George, MD, and Sherry M. Wren, MD, of Stanford (Calif.) University wrote that the study “demonstrates how variables, besides coexisting medical diseases, can affect surgical outcomes.”

“Metformin now joins beta-blockers, statins, and immunonutrition as preoperative agents associated with improved surgical outcomes,” they wrote, adding that future studies should factor in statin use and whether those and other medications should be continued postoperatively because metformin is often held after surgery owing to concerns about contrast agent interactions, whereas statin continuation is recommended.

Future studies of metformin in this setting should exclude patients who are taking statins, or look at possible interactions between the two agents, they said, adding that they would be “interested in seeing a subanalysis of this data set that excludes patients who were prescribed statins.”

“Those data would further solidify the role of metformin as a possible modifiable perioperative factor,” they wrote.

The study was funded by the University of Pittsburgh Medical Center and by grants from the National Heart, Lung, and Blood Institute and the National Institutes of Health. Dr. Reitz reported having no disclosures. Dr. George and Dr. Wren also reported having no disclosures.
 

[email protected]

SOURCE: Reitz K et al. JAMA Surg. 2020 Apr 8. doi: 10.1001/jamasurg.2020.0416.

Patients with type 2 diabetes who take metformin may have lower risk-adjusted mortality and readmission rates after surgery than do those who don’t take metformin, findings from a large retrospective cohort study suggest.

Of 10,088 individuals with diabetes who underwent a major surgery requiring hospital admission between January 1, 2010, and January 1, 2016, a total of 5,962 (59%) had received a prescription for metformin in the 180 days before surgery, and 5,460 of those patients were propensity score–matched to controls who did not receive a metformin prescription.

The study participants had a mean age of 67.7 years and underwent surgery requiring general anesthesia and postoperative admission at any of 15 hospitals in a single Pennsylvania health system. In addition to being prescribed metformin within 180 days before surgery, they also had metformin on their list of active medications at their most recent preoperative encounter before the surgery. The were followed until December 18, 2018.

In all, the 90-day and 5-year mortality hazards were reduced by 28% and 26%, respectively, in the metformin prescription recipients, compared with the propensity score–matched controls (hazard ratios, 0.72 and 0.74, respectively), Katherine M. Reitz, MD, and colleagues at the University of Pittsburgh reported in JAMA Surgery.

The readmission hazard – with mortality as a competing risk – was reduced by 16% at 30 days and 14% at 90 days (sub-HRs, 0.84 and 0.86, respectively), the researchers found.

“Hospital readmissions among those with preoperative metformin prescriptions were observed by postdischarge days 30 and 90 (304 [11%] and 538 [20.1%], respectively), whereas among those without prescriptions, 361 readmissions (13%) occurred by day 30 and 614 (23%) by day 90,” they wrote.

The investigators also noted that inflammation was reduced in patients who received a metformin prescription, compared with those who did not (mean preoperative neutrophil to leukocyte ratio, 4.5 vs. 5.0, respectively).

“In the full cohort, multivariable regression analysis similarly demonstrated that metformin was associated with a reduced hazard for both 90-day and 5-year mortality (adjusted HRs, 0.77 and 0.80, respectively) and for 30-day and 90-day readmission (aHR, 0.83 and 0.86), with mortality as a competing risk,” they added.

The findings support those from previous studies showing a decrease in all-cause mortality among diabetes patients taking metformin, said the researchers, noting that those patients had fewer age-related chronic diseases.

“These associations may reflect the anti-aging properties of metformin against the onset of disease or diabetes-associated complications. This study extends these finding by demonstrating that preoperative metformin prescriptions were associated with a reduction in postoperative mortality and readmission, a surrogate for postoperative complications, and with long-term mortality,” they wrote.

The study was limited by a number of factors, such as the potential for residual confounding inherent in retrospective analyses and a lack of adequate power to evaluate the association between metformin use and outcomes for individual surgical procedures. But the authors added that the findings are of note, because adults with comorbidities, such as diabetes, have less physiological reserve and an increased postoperative mortality and readmission rate. The results, therefore, warrant investigation with a prospective randomized clinical trial, they concluded.

In an accompanying editorial, Elizabeth L. George, MD, and Sherry M. Wren, MD, of Stanford (Calif.) University wrote that the study “demonstrates how variables, besides coexisting medical diseases, can affect surgical outcomes.”

“Metformin now joins beta-blockers, statins, and immunonutrition as preoperative agents associated with improved surgical outcomes,” they wrote, adding that future studies should factor in statin use and whether those and other medications should be continued postoperatively because metformin is often held after surgery owing to concerns about contrast agent interactions, whereas statin continuation is recommended.

Future studies of metformin in this setting should exclude patients who are taking statins, or look at possible interactions between the two agents, they said, adding that they would be “interested in seeing a subanalysis of this data set that excludes patients who were prescribed statins.”

“Those data would further solidify the role of metformin as a possible modifiable perioperative factor,” they wrote.

The study was funded by the University of Pittsburgh Medical Center and by grants from the National Heart, Lung, and Blood Institute and the National Institutes of Health. Dr. Reitz reported having no disclosures. Dr. George and Dr. Wren also reported having no disclosures.
 

[email protected]

SOURCE: Reitz K et al. JAMA Surg. 2020 Apr 8. doi: 10.1001/jamasurg.2020.0416.

Patients with type 2 diabetes who take metformin may have lower risk-adjusted mortality and readmission rates after surgery than do those who don’t take metformin, findings from a large retrospective cohort study suggest.

Of 10,088 individuals with diabetes who underwent a major surgery requiring hospital admission between January 1, 2010, and January 1, 2016, a total of 5,962 (59%) had received a prescription for metformin in the 180 days before surgery, and 5,460 of those patients were propensity score–matched to controls who did not receive a metformin prescription.

The study participants had a mean age of 67.7 years and underwent surgery requiring general anesthesia and postoperative admission at any of 15 hospitals in a single Pennsylvania health system. In addition to being prescribed metformin within 180 days before surgery, they also had metformin on their list of active medications at their most recent preoperative encounter before the surgery. The were followed until December 18, 2018.

In all, the 90-day and 5-year mortality hazards were reduced by 28% and 26%, respectively, in the metformin prescription recipients, compared with the propensity score–matched controls (hazard ratios, 0.72 and 0.74, respectively), Katherine M. Reitz, MD, and colleagues at the University of Pittsburgh reported in JAMA Surgery.

The readmission hazard – with mortality as a competing risk – was reduced by 16% at 30 days and 14% at 90 days (sub-HRs, 0.84 and 0.86, respectively), the researchers found.

“Hospital readmissions among those with preoperative metformin prescriptions were observed by postdischarge days 30 and 90 (304 [11%] and 538 [20.1%], respectively), whereas among those without prescriptions, 361 readmissions (13%) occurred by day 30 and 614 (23%) by day 90,” they wrote.

The investigators also noted that inflammation was reduced in patients who received a metformin prescription, compared with those who did not (mean preoperative neutrophil to leukocyte ratio, 4.5 vs. 5.0, respectively).

“In the full cohort, multivariable regression analysis similarly demonstrated that metformin was associated with a reduced hazard for both 90-day and 5-year mortality (adjusted HRs, 0.77 and 0.80, respectively) and for 30-day and 90-day readmission (aHR, 0.83 and 0.86), with mortality as a competing risk,” they added.

The findings support those from previous studies showing a decrease in all-cause mortality among diabetes patients taking metformin, said the researchers, noting that those patients had fewer age-related chronic diseases.

“These associations may reflect the anti-aging properties of metformin against the onset of disease or diabetes-associated complications. This study extends these finding by demonstrating that preoperative metformin prescriptions were associated with a reduction in postoperative mortality and readmission, a surrogate for postoperative complications, and with long-term mortality,” they wrote.

The study was limited by a number of factors, such as the potential for residual confounding inherent in retrospective analyses and a lack of adequate power to evaluate the association between metformin use and outcomes for individual surgical procedures. But the authors added that the findings are of note, because adults with comorbidities, such as diabetes, have less physiological reserve and an increased postoperative mortality and readmission rate. The results, therefore, warrant investigation with a prospective randomized clinical trial, they concluded.

In an accompanying editorial, Elizabeth L. George, MD, and Sherry M. Wren, MD, of Stanford (Calif.) University wrote that the study “demonstrates how variables, besides coexisting medical diseases, can affect surgical outcomes.”

“Metformin now joins beta-blockers, statins, and immunonutrition as preoperative agents associated with improved surgical outcomes,” they wrote, adding that future studies should factor in statin use and whether those and other medications should be continued postoperatively because metformin is often held after surgery owing to concerns about contrast agent interactions, whereas statin continuation is recommended.

Future studies of metformin in this setting should exclude patients who are taking statins, or look at possible interactions between the two agents, they said, adding that they would be “interested in seeing a subanalysis of this data set that excludes patients who were prescribed statins.”

“Those data would further solidify the role of metformin as a possible modifiable perioperative factor,” they wrote.

The study was funded by the University of Pittsburgh Medical Center and by grants from the National Heart, Lung, and Blood Institute and the National Institutes of Health. Dr. Reitz reported having no disclosures. Dr. George and Dr. Wren also reported having no disclosures.
 

[email protected]

SOURCE: Reitz K et al. JAMA Surg. 2020 Apr 8. doi: 10.1001/jamasurg.2020.0416.

Given the possibility that children with hematologic malignancies may have increased susceptibility to coronavirus disease 2019 (COVID-19), clinicians from China and the United States have proposed a plan for preventing and managing outbreaks in hospitals’ pediatric hematology and oncology departments.

The plan is focused primarily on infection prevention and control strategies, Yulei He, MD, of Chengdu (China) Women’s and Children’s Central Hospital and colleagues explained in an article published in The Lancet Haematology.

The authors noted that close contact with COVID-19 patients is thought to be the main route of transmission, and a retrospective study indicated that 41.3% of initial COVID-19 cases were caused by hospital-related transmission.

“Children with hematological malignancies might have increased susceptibility to infection with SARS-CoV-2 because of immunodeficiency; therefore, procedures are needed to avoid hospital-related transmission and infection for these patients,” the authors wrote.
 

Preventing the spread of infection

Dr. He and colleagues advised that medical staff be kept up-to-date with the latest information about COVID-19 and perform assessments regularly to identify cases in their departments.

The authors also recommended establishing a COVID-19 expert committee – consisting of infectious disease physicians, hematologists, oncologists, radiologists, pharmacists, and hospital infection control staff – to make medical decisions in multidisciplinary consultation meetings. In addition, the authors recommended regional management strategies be adopted to minimize cross infection within the hospital. Specifically, the authors proposed creating the following four zones:

1. A surveillance and screening zone for patients potentially infected with SARS-CoV-2

2. A suspected-case quarantine zone where patients thought to have COVID-19 are isolated in single rooms

3. A confirmed-case quarantine zone where patients are treated for COVID-19

4. A hematology/oncology ward for treating non–COVID-19 patients with malignancies.

Dr. He and colleagues also stressed the importance of providing personal protective equipment for all zones, along with instructions for proper use and disposal. The authors recommended developing and following specific protocols for outpatient visits in the hematology/oncology ward, and providing COVID-19 prevention and control information to families and health care workers.
 

Managing cancer treatment

For patients with acute leukemias who have induction chemotherapy planned, Dr. He and colleagues argued that scheduled chemotherapy should not be interrupted unless COVID-19 is suspected or diagnosed. The authors said treatment should not be delayed more than 7 days during induction, consolidation, or the intermediate phase of chemotherapy because the virus has an incubation period of 2-7 days. This will allow a short period of observation to screen for potential infection.

The authors recommended that patients with lymphoma and solid tumors first undergo COVID-19 screening and then receive treatment in hematology/oncology wards “according to their chemotherapy schedule, and without delay, until they are in complete remission.”

“If the patient is in complete remission, we recommend a treatment delay of no more than 7 days to allow a short period of observation to screen for COVID-19,” the authors added.

Maintenance chemotherapy should not be delayed for more than 14 days, Dr. He and colleagues wrote. “This increase in the maximum delay before chemotherapy strikes a balance between the potential risk of SARS-CoV-2 infection and tumor recurrence, since pediatric patients in this phase of treatment have a reduced risk of tumor recurrence,” the authors added.
 

Caring for patients with COVID-19

For inpatients diagnosed with COVID-19, Dr. He and colleagues recommended the following:

• Prioritize COVID-19 treatment for children with primary disease remission.
• For children not in remission, prioritize treatment for critical patients.
• Isolated patients should be treated for COVID-19, and their chemotherapy should be temporarily suspended or reduced in intensity..

Dr. He and colleagues noted that, by following these recommendations for infection prevention, they had no cases of COVID-19 among children in their hematology/oncology departments. However, the authors said the recommendations “could fail to some extent” based on “differences in medical resources, health care settings, and the policy of the specific government.”

The authors said their recommendations should be updated continuously as new information and clinical evidence emerges.

Dr. He and colleagues reported having no conflicts of interest.

[email protected]

SOURCE: He Y et al. Lancet Haematol. doi: 10/1016/s2352-3026(20)30104-6.

Given the possibility that children with hematologic malignancies may have increased susceptibility to coronavirus disease 2019 (COVID-19), clinicians from China and the United States have proposed a plan for preventing and managing outbreaks in hospitals’ pediatric hematology and oncology departments.

The plan is focused primarily on infection prevention and control strategies, Yulei He, MD, of Chengdu (China) Women’s and Children’s Central Hospital and colleagues explained in an article published in The Lancet Haematology.

The authors noted that close contact with COVID-19 patients is thought to be the main route of transmission, and a retrospective study indicated that 41.3% of initial COVID-19 cases were caused by hospital-related transmission.

“Children with hematological malignancies might have increased susceptibility to infection with SARS-CoV-2 because of immunodeficiency; therefore, procedures are needed to avoid hospital-related transmission and infection for these patients,” the authors wrote.
 

Preventing the spread of infection

Dr. He and colleagues advised that medical staff be kept up-to-date with the latest information about COVID-19 and perform assessments regularly to identify cases in their departments.

The authors also recommended establishing a COVID-19 expert committee – consisting of infectious disease physicians, hematologists, oncologists, radiologists, pharmacists, and hospital infection control staff – to make medical decisions in multidisciplinary consultation meetings. In addition, the authors recommended regional management strategies be adopted to minimize cross infection within the hospital. Specifically, the authors proposed creating the following four zones:

1. A surveillance and screening zone for patients potentially infected with SARS-CoV-2

2. A suspected-case quarantine zone where patients thought to have COVID-19 are isolated in single rooms

3. A confirmed-case quarantine zone where patients are treated for COVID-19

4. A hematology/oncology ward for treating non–COVID-19 patients with malignancies.

Dr. He and colleagues also stressed the importance of providing personal protective equipment for all zones, along with instructions for proper use and disposal. The authors recommended developing and following specific protocols for outpatient visits in the hematology/oncology ward, and providing COVID-19 prevention and control information to families and health care workers.
 

Managing cancer treatment

For patients with acute leukemias who have induction chemotherapy planned, Dr. He and colleagues argued that scheduled chemotherapy should not be interrupted unless COVID-19 is suspected or diagnosed. The authors said treatment should not be delayed more than 7 days during induction, consolidation, or the intermediate phase of chemotherapy because the virus has an incubation period of 2-7 days. This will allow a short period of observation to screen for potential infection.

The authors recommended that patients with lymphoma and solid tumors first undergo COVID-19 screening and then receive treatment in hematology/oncology wards “according to their chemotherapy schedule, and without delay, until they are in complete remission.”

“If the patient is in complete remission, we recommend a treatment delay of no more than 7 days to allow a short period of observation to screen for COVID-19,” the authors added.

Maintenance chemotherapy should not be delayed for more than 14 days, Dr. He and colleagues wrote. “This increase in the maximum delay before chemotherapy strikes a balance between the potential risk of SARS-CoV-2 infection and tumor recurrence, since pediatric patients in this phase of treatment have a reduced risk of tumor recurrence,” the authors added.
 

Caring for patients with COVID-19

For inpatients diagnosed with COVID-19, Dr. He and colleagues recommended the following:

• Prioritize COVID-19 treatment for children with primary disease remission.
• For children not in remission, prioritize treatment for critical patients.
• Isolated patients should be treated for COVID-19, and their chemotherapy should be temporarily suspended or reduced in intensity..

Dr. He and colleagues noted that, by following these recommendations for infection prevention, they had no cases of COVID-19 among children in their hematology/oncology departments. However, the authors said the recommendations “could fail to some extent” based on “differences in medical resources, health care settings, and the policy of the specific government.”

The authors said their recommendations should be updated continuously as new information and clinical evidence emerges.

Dr. He and colleagues reported having no conflicts of interest.

[email protected]

SOURCE: He Y et al. Lancet Haematol. doi: 10/1016/s2352-3026(20)30104-6.

Given the possibility that children with hematologic malignancies may have increased susceptibility to coronavirus disease 2019 (COVID-19), clinicians from China and the United States have proposed a plan for preventing and managing outbreaks in hospitals’ pediatric hematology and oncology departments.

The plan is focused primarily on infection prevention and control strategies, Yulei He, MD, of Chengdu (China) Women’s and Children’s Central Hospital and colleagues explained in an article published in The Lancet Haematology.

The authors noted that close contact with COVID-19 patients is thought to be the main route of transmission, and a retrospective study indicated that 41.3% of initial COVID-19 cases were caused by hospital-related transmission.

“Children with hematological malignancies might have increased susceptibility to infection with SARS-CoV-2 because of immunodeficiency; therefore, procedures are needed to avoid hospital-related transmission and infection for these patients,” the authors wrote.
 

Preventing the spread of infection

Dr. He and colleagues advised that medical staff be kept up-to-date with the latest information about COVID-19 and perform assessments regularly to identify cases in their departments.

The authors also recommended establishing a COVID-19 expert committee – consisting of infectious disease physicians, hematologists, oncologists, radiologists, pharmacists, and hospital infection control staff – to make medical decisions in multidisciplinary consultation meetings. In addition, the authors recommended regional management strategies be adopted to minimize cross infection within the hospital. Specifically, the authors proposed creating the following four zones:

1. A surveillance and screening zone for patients potentially infected with SARS-CoV-2

2. A suspected-case quarantine zone where patients thought to have COVID-19 are isolated in single rooms

3. A confirmed-case quarantine zone where patients are treated for COVID-19

4. A hematology/oncology ward for treating non–COVID-19 patients with malignancies.

Dr. He and colleagues also stressed the importance of providing personal protective equipment for all zones, along with instructions for proper use and disposal. The authors recommended developing and following specific protocols for outpatient visits in the hematology/oncology ward, and providing COVID-19 prevention and control information to families and health care workers.
 

Managing cancer treatment

For patients with acute leukemias who have induction chemotherapy planned, Dr. He and colleagues argued that scheduled chemotherapy should not be interrupted unless COVID-19 is suspected or diagnosed. The authors said treatment should not be delayed more than 7 days during induction, consolidation, or the intermediate phase of chemotherapy because the virus has an incubation period of 2-7 days. This will allow a short period of observation to screen for potential infection.

The authors recommended that patients with lymphoma and solid tumors first undergo COVID-19 screening and then receive treatment in hematology/oncology wards “according to their chemotherapy schedule, and without delay, until they are in complete remission.”

“If the patient is in complete remission, we recommend a treatment delay of no more than 7 days to allow a short period of observation to screen for COVID-19,” the authors added.

Maintenance chemotherapy should not be delayed for more than 14 days, Dr. He and colleagues wrote. “This increase in the maximum delay before chemotherapy strikes a balance between the potential risk of SARS-CoV-2 infection and tumor recurrence, since pediatric patients in this phase of treatment have a reduced risk of tumor recurrence,” the authors added.
 

Caring for patients with COVID-19

For inpatients diagnosed with COVID-19, Dr. He and colleagues recommended the following:

• Prioritize COVID-19 treatment for children with primary disease remission.
• For children not in remission, prioritize treatment for critical patients.
• Isolated patients should be treated for COVID-19, and their chemotherapy should be temporarily suspended or reduced in intensity..

Dr. He and colleagues noted that, by following these recommendations for infection prevention, they had no cases of COVID-19 among children in their hematology/oncology departments. However, the authors said the recommendations “could fail to some extent” based on “differences in medical resources, health care settings, and the policy of the specific government.”

The authors said their recommendations should be updated continuously as new information and clinical evidence emerges.

Dr. He and colleagues reported having no conflicts of interest.

[email protected]

SOURCE: He Y et al. Lancet Haematol. doi: 10/1016/s2352-3026(20)30104-6.