Key clinical point: Azacitidine was safe but had no significant impact on relapse-free survival after transplant in in patients with acute myeloid leukemia/myelodysplastic syndrome 

Major finding: Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs. 1.28 years in the control group (P = .19). 

Study details: The data come from a phase 3 open-label randomized trial of 187 patients aged 18 to 75 years with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS); patients received 32 mg/m2 of azacitidine daily for 5 days every 28 days for 12 cycles.

Disclosures: The study was supported by Celgene Pharmaceuticals. Lead author Dr. Oran disclosed serving as a consultant for Celgene and receiving research funding from AROG Pharmaceuticals and Astex Pharmaceuticals.

Source: Oran B et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020002544.

Key clinical point: Azacitidine was safe but had no significant impact on relapse-free survival after transplant in in patients with acute myeloid leukemia/myelodysplastic syndrome 

Major finding: Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs. 1.28 years in the control group (P = .19). 

Study details: The data come from a phase 3 open-label randomized trial of 187 patients aged 18 to 75 years with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS); patients received 32 mg/m2 of azacitidine daily for 5 days every 28 days for 12 cycles.

Disclosures: The study was supported by Celgene Pharmaceuticals. Lead author Dr. Oran disclosed serving as a consultant for Celgene and receiving research funding from AROG Pharmaceuticals and Astex Pharmaceuticals.

Source: Oran B et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020002544.

Key clinical point: Azacitidine was safe but had no significant impact on relapse-free survival after transplant in in patients with acute myeloid leukemia/myelodysplastic syndrome 

Major finding: Median relapse-free survival (RFS) was 2.07 years in the azacitidine group vs. 1.28 years in the control group (P = .19). 

Study details: The data come from a phase 3 open-label randomized trial of 187 patients aged 18 to 75 years with acute myeloid leukemia/myelodysplastic syndrome (AML/MDS); patients received 32 mg/m2 of azacitidine daily for 5 days every 28 days for 12 cycles.

Disclosures: The study was supported by Celgene Pharmaceuticals. Lead author Dr. Oran disclosed serving as a consultant for Celgene and receiving research funding from AROG Pharmaceuticals and Astex Pharmaceuticals.

Source: Oran B et al. Blood Adv. 2020 Nov 10. doi: 10.1182/bloodadvances.2020002544.

Key clinical point: Imetelstat increased transfusion independence for patients with lower risk myelodysplastic syndromes who were resistant or refractory to treatment with erythropoiesis-stimulating agent.

Major finding: At 8 weeks, 37% of the patients were red blood cell transfusion independent, with an average duration of 65 weeks.

Study details: The data come from a phase II study of 57 adult patients with lower-risk myelodysplastic syndromes dependent on red blood cell transfusion and relapsed or refractory to erythropoiesis-stimulating agent; patients received imetelstat with a primary endpoint of red blood cell transfusion independence at 8 weeks.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Steensma DP et al. J Clin Oncol. 2020 Oct 27. doi: 10.1200/JCO.20.01895. 

Key clinical point: Imetelstat increased transfusion independence for patients with lower risk myelodysplastic syndromes who were resistant or refractory to treatment with erythropoiesis-stimulating agent.

Major finding: At 8 weeks, 37% of the patients were red blood cell transfusion independent, with an average duration of 65 weeks.

Study details: The data come from a phase II study of 57 adult patients with lower-risk myelodysplastic syndromes dependent on red blood cell transfusion and relapsed or refractory to erythropoiesis-stimulating agent; patients received imetelstat with a primary endpoint of red blood cell transfusion independence at 8 weeks.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Steensma DP et al. J Clin Oncol. 2020 Oct 27. doi: 10.1200/JCO.20.01895. 

Key clinical point: Imetelstat increased transfusion independence for patients with lower risk myelodysplastic syndromes who were resistant or refractory to treatment with erythropoiesis-stimulating agent.

Major finding: At 8 weeks, 37% of the patients were red blood cell transfusion independent, with an average duration of 65 weeks.

Study details: The data come from a phase II study of 57 adult patients with lower-risk myelodysplastic syndromes dependent on red blood cell transfusion and relapsed or refractory to erythropoiesis-stimulating agent; patients received imetelstat with a primary endpoint of red blood cell transfusion independence at 8 weeks.

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Steensma DP et al. J Clin Oncol. 2020 Oct 27. doi: 10.1200/JCO.20.01895. 

Key clinical point: Food supplements coenzyme Q10 and carnitine significantly improved mitochondrial respiration in patients with low-risk myelodysplastic syndrome

Major finding: A total of 6 patients (21.4%) achieved hematological improvement based on the International Working Group (IWG) response criteria for MDS after 6 months.

Study details: The data come from an open-label study of 33 adults with myelodysplastic syndrome aged 56 to 93 years who received a combination of coenzyme Q10 at 180 mg/day L-carnitine at 2000 mg/ day, and a standard vitamin-mineral complex daily.

Disclosures: The study was supported by the Rising Tide Foundation and Israel Society of Hematology and Blood Transfusion. The researchers had no financial conflicts to disclose.

Source: Filanovsky K et al. Mediterr J Hemtol Infec Dis. 2020 Nov 1. doi: 10.4084/MJHID.2020.072.

Key clinical point: Food supplements coenzyme Q10 and carnitine significantly improved mitochondrial respiration in patients with low-risk myelodysplastic syndrome

Major finding: A total of 6 patients (21.4%) achieved hematological improvement based on the International Working Group (IWG) response criteria for MDS after 6 months.

Study details: The data come from an open-label study of 33 adults with myelodysplastic syndrome aged 56 to 93 years who received a combination of coenzyme Q10 at 180 mg/day L-carnitine at 2000 mg/ day, and a standard vitamin-mineral complex daily.

Disclosures: The study was supported by the Rising Tide Foundation and Israel Society of Hematology and Blood Transfusion. The researchers had no financial conflicts to disclose.

Source: Filanovsky K et al. Mediterr J Hemtol Infec Dis. 2020 Nov 1. doi: 10.4084/MJHID.2020.072.

Key clinical point: Food supplements coenzyme Q10 and carnitine significantly improved mitochondrial respiration in patients with low-risk myelodysplastic syndrome

Major finding: A total of 6 patients (21.4%) achieved hematological improvement based on the International Working Group (IWG) response criteria for MDS after 6 months.

Study details: The data come from an open-label study of 33 adults with myelodysplastic syndrome aged 56 to 93 years who received a combination of coenzyme Q10 at 180 mg/day L-carnitine at 2000 mg/ day, and a standard vitamin-mineral complex daily.

Disclosures: The study was supported by the Rising Tide Foundation and Israel Society of Hematology and Blood Transfusion. The researchers had no financial conflicts to disclose.

Source: Filanovsky K et al. Mediterr J Hemtol Infec Dis. 2020 Nov 1. doi: 10.4084/MJHID.2020.072.

Key clinical point: The financial burden of monthly azacitidine must be weighed against the benefits of treatment, but patients with acute myeloid leukemia and myelodysplastic syndrome have few options.

Major finding: A total of 31 patients with measurable residual disease at baseline were relapse-free and alive after 6 months of monthly injection treatment with azacitidine.

Study details: The data come from a review of the pros and cons of the RELAZA-2, a German-multicentered, open-label, single-arm, phase II study of azacitidine in 53 adult patients who developed measurable residual disease after treatment for acute myeloid leukemia or advanced myelodysplastic syndrome; 29 after chemotherapy and 24 after allogeneic hematopoietic stem cell transplantation (ASCT).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Pan J et al. Front Oncol. 2020 Oct 22. doi: 10.3389/fonc.2020.576924.

Key clinical point: The financial burden of monthly azacitidine must be weighed against the benefits of treatment, but patients with acute myeloid leukemia and myelodysplastic syndrome have few options.

Major finding: A total of 31 patients with measurable residual disease at baseline were relapse-free and alive after 6 months of monthly injection treatment with azacitidine.

Study details: The data come from a review of the pros and cons of the RELAZA-2, a German-multicentered, open-label, single-arm, phase II study of azacitidine in 53 adult patients who developed measurable residual disease after treatment for acute myeloid leukemia or advanced myelodysplastic syndrome; 29 after chemotherapy and 24 after allogeneic hematopoietic stem cell transplantation (ASCT).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Pan J et al. Front Oncol. 2020 Oct 22. doi: 10.3389/fonc.2020.576924.

Key clinical point: The financial burden of monthly azacitidine must be weighed against the benefits of treatment, but patients with acute myeloid leukemia and myelodysplastic syndrome have few options.

Major finding: A total of 31 patients with measurable residual disease at baseline were relapse-free and alive after 6 months of monthly injection treatment with azacitidine.

Study details: The data come from a review of the pros and cons of the RELAZA-2, a German-multicentered, open-label, single-arm, phase II study of azacitidine in 53 adult patients who developed measurable residual disease after treatment for acute myeloid leukemia or advanced myelodysplastic syndrome; 29 after chemotherapy and 24 after allogeneic hematopoietic stem cell transplantation (ASCT).

Disclosures: The study received no outside funding. The researchers had no financial conflicts to disclose.

Source: Pan J et al. Front Oncol. 2020 Oct 22. doi: 10.3389/fonc.2020.576924.

Key clinical point: A novel retinoic acid receptor alpha agonist appeared safe in a phase 1 study of patients with relapsed and refractory high-grade myelodysplastic syndrome or acute myelogenous leukemia.

Major finding: A total of 4 of 11 patients (36%) had stable disease or better after two 28-day treatment cycles; the study ended early because of an inadequate supply of the drug.

Study details: The data come from a phase 1 dose-escalation study of the novel retinoic acid receptor alpha agonist IRX195183; 11 adults aged 18 to 60 years with relapsed or refractory myelodysplastic syndrome or acute myelogenous leukemia received the drug for two 28-day cycles with dosage starting at 50 mg daily or 75 mg daily.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Leukemia and Lymphoma Society, and the Augustine Fellowship. IRX195183 was provided by Io Therapeutics, Inc. Lead author Dr. Ambinder had no financial conflicts to disclose. Several coauthors are authors on a patent for the use of IRX195183.

Source: Ambinder AJ et al. Front Oncol. 2020 Oct 23. doi: 10.3389/fonc.2020.587062.

Key clinical point: A novel retinoic acid receptor alpha agonist appeared safe in a phase 1 study of patients with relapsed and refractory high-grade myelodysplastic syndrome or acute myelogenous leukemia.

Major finding: A total of 4 of 11 patients (36%) had stable disease or better after two 28-day treatment cycles; the study ended early because of an inadequate supply of the drug.

Study details: The data come from a phase 1 dose-escalation study of the novel retinoic acid receptor alpha agonist IRX195183; 11 adults aged 18 to 60 years with relapsed or refractory myelodysplastic syndrome or acute myelogenous leukemia received the drug for two 28-day cycles with dosage starting at 50 mg daily or 75 mg daily.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Leukemia and Lymphoma Society, and the Augustine Fellowship. IRX195183 was provided by Io Therapeutics, Inc. Lead author Dr. Ambinder had no financial conflicts to disclose. Several coauthors are authors on a patent for the use of IRX195183.

Source: Ambinder AJ et al. Front Oncol. 2020 Oct 23. doi: 10.3389/fonc.2020.587062.

Key clinical point: A novel retinoic acid receptor alpha agonist appeared safe in a phase 1 study of patients with relapsed and refractory high-grade myelodysplastic syndrome or acute myelogenous leukemia.

Major finding: A total of 4 of 11 patients (36%) had stable disease or better after two 28-day treatment cycles; the study ended early because of an inadequate supply of the drug.

Study details: The data come from a phase 1 dose-escalation study of the novel retinoic acid receptor alpha agonist IRX195183; 11 adults aged 18 to 60 years with relapsed or refractory myelodysplastic syndrome or acute myelogenous leukemia received the drug for two 28-day cycles with dosage starting at 50 mg daily or 75 mg daily.

Disclosures: The study was supported by the National Heart, Lung, and Blood Institute, the National Cancer Institute, the Leukemia and Lymphoma Society, and the Augustine Fellowship. IRX195183 was provided by Io Therapeutics, Inc. Lead author Dr. Ambinder had no financial conflicts to disclose. Several coauthors are authors on a patent for the use of IRX195183.

Source: Ambinder AJ et al. Front Oncol. 2020 Oct 23. doi: 10.3389/fonc.2020.587062.

The Department of Health & Human Services is proposing an overhaul of HIPAA that will make it easier to access patients’ personal health information, including the health records of patients with mental illness. The proposal would also do away with the requirement that all patients sign a notice of privacy practices.

The changes are contained in a 357-page proposed rule, which was unveiled by federal officials Dec. 10. Roger Severino, director of HHS’ Office for Civil Rights, said in a briefing that the sweeping proposal would empower patients, reduce the administrative burden for health care providers, and pave the way to better-coordinated care.

HHS estimated that the rule could save $3.2 billion over 5 years, but it’s not clear how much of that would accrue to clinical practices.

The most obvious cost-saving aspect for medical and dental practices is the proposal that practitioners would no longer have to provide and collect signed notifications of privacy practices.

“This has been a tremendous waste of time and effort and has caused massive confusion,” said Mr. Severino. He said some patients thought they were waiving privacy rights and that, in some cases, physicians refused to administer care unless patients signed the notices. “That was never the intent.”

Requiring that patients sign the form and that practices keep copies for 6 years is an “unnecessary burden,” said Mr. Severino. “We’ve lost whole forests from this regulation.”

Under the new proposal, health care providers would merely have to let patients know where to find their privacy policies.
 

Sharing mental health info

The rule would also ease the standard for sharing information about a patient who is in a mental health crisis, such as an exacerbation of a serious mental illness or a crisis related to a substance use disorder, including an overdose.

Currently, clinicians can choose to disclose protected health information – to a family member, a caregiver, a law enforcement official, a doctor, or an insurer – if they believe that doing so is advisable in their “professional judgment.” The rule proposes to ease that to a “good faith” belief that a disclosure would be in the best interest of the patient. In both instances, the patient can still object and block the disclosure.

As an example, HHS said that, in the case of a young adult who had experienced an overdose of opioids, a licensed health care professional could make the determination to “disclose relevant information to a parent who is involved in the patient’s treatment and who the young adult would expect, based on their relationship, to participate in or be involved with the patient’s recovery from the overdose.”

HHS is also proposing to let clinicians disclose information in cases in which an individual might be a threat to himself or others, provided the harm is “serious and reasonably foreseeable.”

Currently, information can only be disclosed if it appears there is a “serious and imminent” threat to health or safety. If an individual experienced suicidal ideation, for instance, a health care professional could notify family that the individual is at risk.
 

Fast, no-cost access

The rule also aims to make it easier for patients to get access to their own health care information quickly – within 15 days of a request – instead of the 30 days currently allowed, and sometimes at no cost.

The 30-day time frame is “a relic of a pre-Internet age that should be dispensed with,” said Mr. Severino.

Patients can also request that a treating physician get his or her records from a clinician who had previously treated the individual. The request would be fulfilled within 15 days, although extensions might be possible.

“That takes away the burden of coordination from the patient and puts it on those parties that are responsible for the actual provision of care and that are better positioned to do that coordination,” Mr. Severino said.

Health care professionals will also have to share with patients a fee schedule for records requests. However, if records are shared through a patient portal with view, download, and transmit capabilities, the provider can’t charge the patient for the time it took to upload the information into the system.

“We do not believe a patient’s personal medical record should be profit centers for providers,” Mr. Severino said.

Patients will be allowed to take photos with a smartphone of personal health information – such as an x-ray or sonogram – while receiving care.

The rule is open for public comment until mid-February. After that, it will become final in 180 days. The agency said it would not begin enforcement until 240 days after the final rule was published.

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

The Department of Health & Human Services is proposing an overhaul of HIPAA that will make it easier to access patients’ personal health information, including the health records of patients with mental illness. The proposal would also do away with the requirement that all patients sign a notice of privacy practices.

The changes are contained in a 357-page proposed rule, which was unveiled by federal officials Dec. 10. Roger Severino, director of HHS’ Office for Civil Rights, said in a briefing that the sweeping proposal would empower patients, reduce the administrative burden for health care providers, and pave the way to better-coordinated care.

HHS estimated that the rule could save $3.2 billion over 5 years, but it’s not clear how much of that would accrue to clinical practices.

The most obvious cost-saving aspect for medical and dental practices is the proposal that practitioners would no longer have to provide and collect signed notifications of privacy practices.

“This has been a tremendous waste of time and effort and has caused massive confusion,” said Mr. Severino. He said some patients thought they were waiving privacy rights and that, in some cases, physicians refused to administer care unless patients signed the notices. “That was never the intent.”

Requiring that patients sign the form and that practices keep copies for 6 years is an “unnecessary burden,” said Mr. Severino. “We’ve lost whole forests from this regulation.”

Under the new proposal, health care providers would merely have to let patients know where to find their privacy policies.
 

Sharing mental health info

The rule would also ease the standard for sharing information about a patient who is in a mental health crisis, such as an exacerbation of a serious mental illness or a crisis related to a substance use disorder, including an overdose.

Currently, clinicians can choose to disclose protected health information – to a family member, a caregiver, a law enforcement official, a doctor, or an insurer – if they believe that doing so is advisable in their “professional judgment.” The rule proposes to ease that to a “good faith” belief that a disclosure would be in the best interest of the patient. In both instances, the patient can still object and block the disclosure.

As an example, HHS said that, in the case of a young adult who had experienced an overdose of opioids, a licensed health care professional could make the determination to “disclose relevant information to a parent who is involved in the patient’s treatment and who the young adult would expect, based on their relationship, to participate in or be involved with the patient’s recovery from the overdose.”

HHS is also proposing to let clinicians disclose information in cases in which an individual might be a threat to himself or others, provided the harm is “serious and reasonably foreseeable.”

Currently, information can only be disclosed if it appears there is a “serious and imminent” threat to health or safety. If an individual experienced suicidal ideation, for instance, a health care professional could notify family that the individual is at risk.
 

Fast, no-cost access

The rule also aims to make it easier for patients to get access to their own health care information quickly – within 15 days of a request – instead of the 30 days currently allowed, and sometimes at no cost.

The 30-day time frame is “a relic of a pre-Internet age that should be dispensed with,” said Mr. Severino.

Patients can also request that a treating physician get his or her records from a clinician who had previously treated the individual. The request would be fulfilled within 15 days, although extensions might be possible.

“That takes away the burden of coordination from the patient and puts it on those parties that are responsible for the actual provision of care and that are better positioned to do that coordination,” Mr. Severino said.

Health care professionals will also have to share with patients a fee schedule for records requests. However, if records are shared through a patient portal with view, download, and transmit capabilities, the provider can’t charge the patient for the time it took to upload the information into the system.

“We do not believe a patient’s personal medical record should be profit centers for providers,” Mr. Severino said.

Patients will be allowed to take photos with a smartphone of personal health information – such as an x-ray or sonogram – while receiving care.

The rule is open for public comment until mid-February. After that, it will become final in 180 days. The agency said it would not begin enforcement until 240 days after the final rule was published.

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

The Department of Health & Human Services is proposing an overhaul of HIPAA that will make it easier to access patients’ personal health information, including the health records of patients with mental illness. The proposal would also do away with the requirement that all patients sign a notice of privacy practices.

The changes are contained in a 357-page proposed rule, which was unveiled by federal officials Dec. 10. Roger Severino, director of HHS’ Office for Civil Rights, said in a briefing that the sweeping proposal would empower patients, reduce the administrative burden for health care providers, and pave the way to better-coordinated care.

HHS estimated that the rule could save $3.2 billion over 5 years, but it’s not clear how much of that would accrue to clinical practices.

The most obvious cost-saving aspect for medical and dental practices is the proposal that practitioners would no longer have to provide and collect signed notifications of privacy practices.

“This has been a tremendous waste of time and effort and has caused massive confusion,” said Mr. Severino. He said some patients thought they were waiving privacy rights and that, in some cases, physicians refused to administer care unless patients signed the notices. “That was never the intent.”

Requiring that patients sign the form and that practices keep copies for 6 years is an “unnecessary burden,” said Mr. Severino. “We’ve lost whole forests from this regulation.”

Under the new proposal, health care providers would merely have to let patients know where to find their privacy policies.
 

Sharing mental health info

The rule would also ease the standard for sharing information about a patient who is in a mental health crisis, such as an exacerbation of a serious mental illness or a crisis related to a substance use disorder, including an overdose.

Currently, clinicians can choose to disclose protected health information – to a family member, a caregiver, a law enforcement official, a doctor, or an insurer – if they believe that doing so is advisable in their “professional judgment.” The rule proposes to ease that to a “good faith” belief that a disclosure would be in the best interest of the patient. In both instances, the patient can still object and block the disclosure.

As an example, HHS said that, in the case of a young adult who had experienced an overdose of opioids, a licensed health care professional could make the determination to “disclose relevant information to a parent who is involved in the patient’s treatment and who the young adult would expect, based on their relationship, to participate in or be involved with the patient’s recovery from the overdose.”

HHS is also proposing to let clinicians disclose information in cases in which an individual might be a threat to himself or others, provided the harm is “serious and reasonably foreseeable.”

Currently, information can only be disclosed if it appears there is a “serious and imminent” threat to health or safety. If an individual experienced suicidal ideation, for instance, a health care professional could notify family that the individual is at risk.
 

Fast, no-cost access

The rule also aims to make it easier for patients to get access to their own health care information quickly – within 15 days of a request – instead of the 30 days currently allowed, and sometimes at no cost.

The 30-day time frame is “a relic of a pre-Internet age that should be dispensed with,” said Mr. Severino.

Patients can also request that a treating physician get his or her records from a clinician who had previously treated the individual. The request would be fulfilled within 15 days, although extensions might be possible.

“That takes away the burden of coordination from the patient and puts it on those parties that are responsible for the actual provision of care and that are better positioned to do that coordination,” Mr. Severino said.

Health care professionals will also have to share with patients a fee schedule for records requests. However, if records are shared through a patient portal with view, download, and transmit capabilities, the provider can’t charge the patient for the time it took to upload the information into the system.

“We do not believe a patient’s personal medical record should be profit centers for providers,” Mr. Severino said.

Patients will be allowed to take photos with a smartphone of personal health information – such as an x-ray or sonogram – while receiving care.

The rule is open for public comment until mid-February. After that, it will become final in 180 days. The agency said it would not begin enforcement until 240 days after the final rule was published.

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

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

Clostridioides difficile (C. diff) infection (CDI) is a pathogen of both humans and animals, and to control it will require an integrated approach that encompasses human health care, veterinary health care, environmental regulation, and public policy. That is the conclusion of a group led by Su-Chen Lim, MD, and Tom Riley, MD, of Edith Cowan University in Australia, who published a review in Clinical Microbiology and Infection.

CDI was generally considered a nuisance infection until the early 21st century, when a hypervirulent fluoroquinolone-resistant strain emerged in North America. The strain is now documented In the United States, Canada, and most countries in Europe.

Another new feature of CDI is increased evidence of community transmission, which was previously rare. This is defined as cases where the patient experienced symptom onset outside the hospital, and had no history of hospitalization in the previous 12 weeks or symptom onset within 48 hours of hospital admission. Community-associated CDI now accounts for 41% of U.S. cases, nearly 30% of Australian cases, and about 14% in Europe, according to recent studies.

Several features of CDI suggest a need for an integrated management plan. The preferred habitat of C. diff is the gastrointestinal track of mammals, and likely colonizes all mammalian neonates. Over time, colonization by other microbes likely crowd it out and prevent overgrowth. But widespread use of antimicrobials in animal production can lead to the creation of an environment resembling that of the neonate, allowing C. diff to expand. That has led to food animals becoming a major C. diff reservoir, and whole-genome studies showed that strains found in humans, food, animals, and the environment are closely related and sometimes genetically indistinguishable, suggesting transmission between humans and animals that may be attributable to contaminated food and environments.

The authors suggest that C. diff infection control should be guided by the One Health initiative, which seeks cooperation between physicians, osteopathic physicians, veterinarians, dentists, nurses, and other scientific and environmental disciplines. The goal is to enhance surveillance and interdisciplinary communication, as well as integrated policies. The authors note that C. diff is often thought of by physicians as primarily a hospital problem, who may be unaware of the increased prevalence of community-acquired disease. It is also a significant problem in agriculture, since as many as 50% of piglets succumb to the disease. Other studies have recently shown that asymptomatic carriers of toxigenic strains are likely to transmit the bacteria to C. diff-negative patients. Asymptomatic carriers cluster with symptomatic patients. In one Cleveland hospital, more than 25% of hospital-associated CDI cases were found to have been colonized prior to admission, suggesting that these were not true hospital-associated cases.

C. diff has been isolated from a wide range of sources, including food animals, meat, seafood, vegetables, household environments, and natural environments like rivers, lakes, and soil. About 20% of calves and 70% of piglets are colonized with C. diff. It has a high prevalence in meat products in the United States, but lower in the Europe, possibly because of different slaughtering practices.

The authors suggest that zoonotic C. diff spread is unlikely to be confined to any geographic region or population, and that widespread C. diff contamination is occurring through food or the environment. This could be occurring because spores can withstand cooking temperatures and disseminate through the air, and even through manure from food animals made into compost or fertilizer.

Veterinary efforts mimicking hospital measures have reduced animal CDI, but there are no rapid diagnostic tests for CDI in animals, making it challenging to control its spread in this context.

The authors call for enhanced antimicrobial stewardship in both human and animal settings, including banning of antimicrobial agents as growth promoters. This has been done in the United States and Europe, but not in Brazil, China, Canada, India, and Australia. They also call for research on inactivation of C. diff spores during waste treatment.

Even better, the authors suggest that vaccines should be developed and employed in both animals and humans. No such vaccine exists in animals, but Pfizer has one for humans in a phase 3 clinical trial, but it does not prevent colonization. Others are in development.

The epidemiology of CDI is an ongoing challenge, with emerging new strains and changing social and environmental conditions. “However, it is with the collaborative efforts of industry partners, policymakers, veterinarians, clinicians, and researchers that CDI needs to be approached, a perfect example of One Health. Opening an interdisciplinary dialogue to address CDI and One Health issues has to be the focus of future studies,” the authors concluded.

Help your patients understand their C. difficile diagnosis by sharing patient education from the AGA GI Patient Center: www.gastro.org/Cdiff. 

SOURCE: SC Lim et al. Clinical Microbiology and Infection. 2020;26:85-863.

With the onset of the COVID-19 pandemic, there has been a rapid uptick in virtual recovery programs and telemedicine counseling sessions for patients with substance use disorders (SUDs). New research shows that these programs are acceptable and effective alternatives to in-person sessions.

FatCamera/E+

Study results from three research teams at the University of South Carolina School of Medicine Greenville (USCSM-G) show that SUD counselors in the state were satisfied with their experience with telehealth and virtual recovery meetings.

In one of the studies, five counselors who utilized a virtual meeting platform after the COVID-19 pandemic made in-person visits unsafe were surveyed. The respondents said they much preferred in-person meetings. However, they could also see that virtual meetings were filling an important need for their patients.

Two other studies echoed the results from the first. Clinicians who were leery of the new technology at first became more enthusiastic after they gained experience using it.

“We have lived in a society where there has been one right way, which has always been in-person meetings for recovery, such as Alcoholics Anonymous. It is a very structured process,” lead author Haley Fulton, a fourth-year medical student at USCSM-G, said in an interview.

“The onset of COVID really upended a lot of things, but ... now there may not be just one right way for recovery. There are alternatives to offer,” Ms. Fulton said.

The findings were presented at the annual meeting of the American Academy of Addiction Psychiatry, which was held online this year because of the pandemic.
 

Huge need

“Virtual meetings may not be ideal, but some version of recovery is better than none. If we can make these meetings accessible to more people, this could promote recovery from substance use disorder,” Ms. Fulton said.

There is a huge need for counseling, and past research has shown that failure to attend meetings can precipitate relapse in many individuals.

In Ms. Fulton’s study, counselors were asked to describe how they perceived the efficacy of virtual recovery meetings, compared with that of in-person meetings.

The investigators analyzed how often certain words, phrases, or issues came up during seven in-person recovery meetings held before the COVID-19 pandemic as well as observational data from seven virtual recovery-support meetings held during the pandemic.

On the pro side, the respondents cited convenience, comfort at home, and increased accessibility to counseling for patients.

In addition, because there was no need to travel, virtual meetings were cost effective. Such meetings could expand the recovery world, inasmuch as individuals could attend recovery meetings in other parts of the country.

Perceived disadvantages included challenges involving technology, because learning new apps such as Zoom could be a problem for some patients. Distractions at home and lack of privacy were also cited, but for many, the most important drawback to virtual meetings was the lessening of emotional connection with others.
 

Impact on SUD treatment

In a second study, another team from USCSM-G reported similar findings when it explored the impact of telehealth on counselors as well as on patients who were undergoing SUD treatment during the pandemic.

Led by fourth-year medical students Elizabeth Whiteside and Kyleigh Connolly, the researchers assessed data from a focus group of six behavioral health counselors representing rural and city agencies throughout South Carolina.

Themes that emerged included concerns about mental health – counselors and patients were experiencing increased stress, depression, and anxiety.

“People had to now home school, there were job layoffs, increased responsibilities at home. Also, Narcan [naloxone] distribution was decreased, and this contributed to rising overdose rates,” Ms. Whiteside said in an interview.

The focus group concluded that the advantages of telehealth included greater ability to accept new patients, an increase in scheduling flexibility, and cost-effectiveness because it obviated the need for child care or transportation.

Disadvantages included problems involving privacy, because for many patients who were undergoing SUD recovery, it was impossible to be alone in a room or a designated area of their own.

The counselors also felt strongly that in-person care was needed for certain patients.

“Before COVID happened, [health care] barriers included transport to the actual center and finding care for children,” Ms. Connolly said in an interview.

“That’s where telehealth really bridged the gap for these people, and it actually became a lot easier for them to get in contact with their counselors, get into group meetings, and access other services,” she said.

Many of the study participants were not very optimistic about telehealth at first, Ms. Connolly noted. “They felt a little odd going on telehealth at first, but by the end, everybody said that they loved having it.”

“One of the things that came out often was that patients felt they could be more open and honest because they weren’t looking their counselor right in the face. They didn’t feel so horrible sharing,” Ms. Whiteside added.

Some counselors reported that some clients shared more details with them and that there was an ease of connecting. If a patient was a few minutes late to an appointment, telehealth would put in a call to find out where that patient was.

The counselors also had the ability to determine which of their patients would be good candidates for telehealth counseling and which patients would not do well with telehealth and would instead need in-patient care.

“This is something that really helped the experience go better for the counselors. They were able to determine which patient fit the mold for telehealth working for them. Obviously, patients who have more acute periods of mental health problems would do better with in-person care,” Ms. Whiteside said.
 

Here to stay?

In the third study from USCSM-G, investigators evaluated data from a focus group of four providers of medications for opioid use disorder (MOUD) who practiced in urban and rural areas throughout the state.

The respondents reflected on their experiences in using telemedicine for prescribing MOUD.

As in the previous studies, the providers had positive experiences with telemedicine. It increased patient access, participation, and satisfaction with treatment, and the benefits of telemedicine outweighed its potential limitations.

Still, technology was cited as a barrier to care, especially in rural areas.

“We found that there was a lack of good internet in certain rural parts of South Carolina, and that lack of the proper electronic devices ... could also make it difficult to access telemedicine,” lead author Kellie Shell said in an interview.

As noted in the other studies, the providers expressed a desire that telemedicine incorporate safeguards that would enable clinicians to identify a particular patient’s location in order that authorities could be dispatched if an emergency were to arise.

The clinicians also said that monitoring for diversion and performing pill counts were more difficult to do via telemedicine.

“We definitely have to improve infrastructure, especially in rural areas, so that all people have access to telemedicine,” Ms. Shell said.

“Overall, the providers were won over with telemedicine, and some predicted telehealth and virtual visits were here to stay, even after COVID,” she added.

The three posters provide useful insight into the potential advantages and disadvantages of telehealth in SUD settings, experts said.
 

Telehealth data ‘very limited’

Commenting on the research, Lewei (Allison) Lin, MD, University of Michigan, Ann Arbor, noted that “there is such limited information” about the use of telehealth for patients with SUD.

“These insights are helpful for us to start understanding the things that need to be considered, including clinician attitudes and perceptions,” said Dr. Lin, who was not involved with the studies.

“It will be key to have data as use of telemedicine increases during COVID-19 to help us see exactly how it should be used and to better understand the actual impacts and whether or not it is increasing accessibility, and for which patients,” she added.

David Kan, MD, chief medical officer at Bright Heart Health, San Ramon, Calif., has had experience with telehealth for SUD and has found that conducting pill counts with his patients has not been a problem.

“The Shell poster covers telemedicine well,” Dr. Kan said in an interview.

However, “I disagree with their point that diversion prevention is harder via telemedicine. In my experience, it is easier, as you can do pill or wrapper counts almost on demand. You can also do daily observed dosing with pill counts if diversion is suspected,” he said.

Dr. Kan also suggested ways to cope with problems involving privacy. “Privacy concerns are always an issue but can be mitigated with headphones and a scan of the room with the telehealth technology if a privacy concern arises.”

He acknowledged that in-person meetings, especially through well-established programs, such as Alcoholics Anonymous (AA), will always be important. But he pointed out that people are finding ways to meet safely and have in-person connections.

“The AA has been providing virtual recovery meetings long before COVID. The common complaint is the loss of fellowship associated with recovery groups. I don’t know of a way to get around this short of vaccines,” Dr. Kan said. However, “people have adapted impressively with masked outdoor meetings and other forms of safe gathering.”

The investigators, Dr. Lin, and Dr. Kan reported no relevant financial relationships.
 

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

With the onset of the COVID-19 pandemic, there has been a rapid uptick in virtual recovery programs and telemedicine counseling sessions for patients with substance use disorders (SUDs). New research shows that these programs are acceptable and effective alternatives to in-person sessions.

FatCamera/E+

Study results from three research teams at the University of South Carolina School of Medicine Greenville (USCSM-G) show that SUD counselors in the state were satisfied with their experience with telehealth and virtual recovery meetings.

In one of the studies, five counselors who utilized a virtual meeting platform after the COVID-19 pandemic made in-person visits unsafe were surveyed. The respondents said they much preferred in-person meetings. However, they could also see that virtual meetings were filling an important need for their patients.

Two other studies echoed the results from the first. Clinicians who were leery of the new technology at first became more enthusiastic after they gained experience using it.

“We have lived in a society where there has been one right way, which has always been in-person meetings for recovery, such as Alcoholics Anonymous. It is a very structured process,” lead author Haley Fulton, a fourth-year medical student at USCSM-G, said in an interview.

“The onset of COVID really upended a lot of things, but ... now there may not be just one right way for recovery. There are alternatives to offer,” Ms. Fulton said.

The findings were presented at the annual meeting of the American Academy of Addiction Psychiatry, which was held online this year because of the pandemic.
 

Huge need

“Virtual meetings may not be ideal, but some version of recovery is better than none. If we can make these meetings accessible to more people, this could promote recovery from substance use disorder,” Ms. Fulton said.

There is a huge need for counseling, and past research has shown that failure to attend meetings can precipitate relapse in many individuals.

In Ms. Fulton’s study, counselors were asked to describe how they perceived the efficacy of virtual recovery meetings, compared with that of in-person meetings.

The investigators analyzed how often certain words, phrases, or issues came up during seven in-person recovery meetings held before the COVID-19 pandemic as well as observational data from seven virtual recovery-support meetings held during the pandemic.

On the pro side, the respondents cited convenience, comfort at home, and increased accessibility to counseling for patients.

In addition, because there was no need to travel, virtual meetings were cost effective. Such meetings could expand the recovery world, inasmuch as individuals could attend recovery meetings in other parts of the country.

Perceived disadvantages included challenges involving technology, because learning new apps such as Zoom could be a problem for some patients. Distractions at home and lack of privacy were also cited, but for many, the most important drawback to virtual meetings was the lessening of emotional connection with others.
 

Impact on SUD treatment

In a second study, another team from USCSM-G reported similar findings when it explored the impact of telehealth on counselors as well as on patients who were undergoing SUD treatment during the pandemic.

Led by fourth-year medical students Elizabeth Whiteside and Kyleigh Connolly, the researchers assessed data from a focus group of six behavioral health counselors representing rural and city agencies throughout South Carolina.

Themes that emerged included concerns about mental health – counselors and patients were experiencing increased stress, depression, and anxiety.

“People had to now home school, there were job layoffs, increased responsibilities at home. Also, Narcan [naloxone] distribution was decreased, and this contributed to rising overdose rates,” Ms. Whiteside said in an interview.

The focus group concluded that the advantages of telehealth included greater ability to accept new patients, an increase in scheduling flexibility, and cost-effectiveness because it obviated the need for child care or transportation.

Disadvantages included problems involving privacy, because for many patients who were undergoing SUD recovery, it was impossible to be alone in a room or a designated area of their own.

The counselors also felt strongly that in-person care was needed for certain patients.

“Before COVID happened, [health care] barriers included transport to the actual center and finding care for children,” Ms. Connolly said in an interview.

“That’s where telehealth really bridged the gap for these people, and it actually became a lot easier for them to get in contact with their counselors, get into group meetings, and access other services,” she said.

Many of the study participants were not very optimistic about telehealth at first, Ms. Connolly noted. “They felt a little odd going on telehealth at first, but by the end, everybody said that they loved having it.”

“One of the things that came out often was that patients felt they could be more open and honest because they weren’t looking their counselor right in the face. They didn’t feel so horrible sharing,” Ms. Whiteside added.

Some counselors reported that some clients shared more details with them and that there was an ease of connecting. If a patient was a few minutes late to an appointment, telehealth would put in a call to find out where that patient was.

The counselors also had the ability to determine which of their patients would be good candidates for telehealth counseling and which patients would not do well with telehealth and would instead need in-patient care.

“This is something that really helped the experience go better for the counselors. They were able to determine which patient fit the mold for telehealth working for them. Obviously, patients who have more acute periods of mental health problems would do better with in-person care,” Ms. Whiteside said.
 

Here to stay?

In the third study from USCSM-G, investigators evaluated data from a focus group of four providers of medications for opioid use disorder (MOUD) who practiced in urban and rural areas throughout the state.

The respondents reflected on their experiences in using telemedicine for prescribing MOUD.

As in the previous studies, the providers had positive experiences with telemedicine. It increased patient access, participation, and satisfaction with treatment, and the benefits of telemedicine outweighed its potential limitations.

Still, technology was cited as a barrier to care, especially in rural areas.

“We found that there was a lack of good internet in certain rural parts of South Carolina, and that lack of the proper electronic devices ... could also make it difficult to access telemedicine,” lead author Kellie Shell said in an interview.

As noted in the other studies, the providers expressed a desire that telemedicine incorporate safeguards that would enable clinicians to identify a particular patient’s location in order that authorities could be dispatched if an emergency were to arise.

The clinicians also said that monitoring for diversion and performing pill counts were more difficult to do via telemedicine.

“We definitely have to improve infrastructure, especially in rural areas, so that all people have access to telemedicine,” Ms. Shell said.

“Overall, the providers were won over with telemedicine, and some predicted telehealth and virtual visits were here to stay, even after COVID,” she added.

The three posters provide useful insight into the potential advantages and disadvantages of telehealth in SUD settings, experts said.
 

Telehealth data ‘very limited’

Commenting on the research, Lewei (Allison) Lin, MD, University of Michigan, Ann Arbor, noted that “there is such limited information” about the use of telehealth for patients with SUD.

“These insights are helpful for us to start understanding the things that need to be considered, including clinician attitudes and perceptions,” said Dr. Lin, who was not involved with the studies.

“It will be key to have data as use of telemedicine increases during COVID-19 to help us see exactly how it should be used and to better understand the actual impacts and whether or not it is increasing accessibility, and for which patients,” she added.

David Kan, MD, chief medical officer at Bright Heart Health, San Ramon, Calif., has had experience with telehealth for SUD and has found that conducting pill counts with his patients has not been a problem.

“The Shell poster covers telemedicine well,” Dr. Kan said in an interview.

However, “I disagree with their point that diversion prevention is harder via telemedicine. In my experience, it is easier, as you can do pill or wrapper counts almost on demand. You can also do daily observed dosing with pill counts if diversion is suspected,” he said.

Dr. Kan also suggested ways to cope with problems involving privacy. “Privacy concerns are always an issue but can be mitigated with headphones and a scan of the room with the telehealth technology if a privacy concern arises.”

He acknowledged that in-person meetings, especially through well-established programs, such as Alcoholics Anonymous (AA), will always be important. But he pointed out that people are finding ways to meet safely and have in-person connections.

“The AA has been providing virtual recovery meetings long before COVID. The common complaint is the loss of fellowship associated with recovery groups. I don’t know of a way to get around this short of vaccines,” Dr. Kan said. However, “people have adapted impressively with masked outdoor meetings and other forms of safe gathering.”

The investigators, Dr. Lin, and Dr. Kan reported no relevant financial relationships.
 

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

With the onset of the COVID-19 pandemic, there has been a rapid uptick in virtual recovery programs and telemedicine counseling sessions for patients with substance use disorders (SUDs). New research shows that these programs are acceptable and effective alternatives to in-person sessions.

FatCamera/E+

Study results from three research teams at the University of South Carolina School of Medicine Greenville (USCSM-G) show that SUD counselors in the state were satisfied with their experience with telehealth and virtual recovery meetings.

In one of the studies, five counselors who utilized a virtual meeting platform after the COVID-19 pandemic made in-person visits unsafe were surveyed. The respondents said they much preferred in-person meetings. However, they could also see that virtual meetings were filling an important need for their patients.

Two other studies echoed the results from the first. Clinicians who were leery of the new technology at first became more enthusiastic after they gained experience using it.

“We have lived in a society where there has been one right way, which has always been in-person meetings for recovery, such as Alcoholics Anonymous. It is a very structured process,” lead author Haley Fulton, a fourth-year medical student at USCSM-G, said in an interview.

“The onset of COVID really upended a lot of things, but ... now there may not be just one right way for recovery. There are alternatives to offer,” Ms. Fulton said.

The findings were presented at the annual meeting of the American Academy of Addiction Psychiatry, which was held online this year because of the pandemic.
 

Huge need

“Virtual meetings may not be ideal, but some version of recovery is better than none. If we can make these meetings accessible to more people, this could promote recovery from substance use disorder,” Ms. Fulton said.

There is a huge need for counseling, and past research has shown that failure to attend meetings can precipitate relapse in many individuals.

In Ms. Fulton’s study, counselors were asked to describe how they perceived the efficacy of virtual recovery meetings, compared with that of in-person meetings.

The investigators analyzed how often certain words, phrases, or issues came up during seven in-person recovery meetings held before the COVID-19 pandemic as well as observational data from seven virtual recovery-support meetings held during the pandemic.

On the pro side, the respondents cited convenience, comfort at home, and increased accessibility to counseling for patients.

In addition, because there was no need to travel, virtual meetings were cost effective. Such meetings could expand the recovery world, inasmuch as individuals could attend recovery meetings in other parts of the country.

Perceived disadvantages included challenges involving technology, because learning new apps such as Zoom could be a problem for some patients. Distractions at home and lack of privacy were also cited, but for many, the most important drawback to virtual meetings was the lessening of emotional connection with others.
 

Impact on SUD treatment

In a second study, another team from USCSM-G reported similar findings when it explored the impact of telehealth on counselors as well as on patients who were undergoing SUD treatment during the pandemic.

Led by fourth-year medical students Elizabeth Whiteside and Kyleigh Connolly, the researchers assessed data from a focus group of six behavioral health counselors representing rural and city agencies throughout South Carolina.

Themes that emerged included concerns about mental health – counselors and patients were experiencing increased stress, depression, and anxiety.

“People had to now home school, there were job layoffs, increased responsibilities at home. Also, Narcan [naloxone] distribution was decreased, and this contributed to rising overdose rates,” Ms. Whiteside said in an interview.

The focus group concluded that the advantages of telehealth included greater ability to accept new patients, an increase in scheduling flexibility, and cost-effectiveness because it obviated the need for child care or transportation.

Disadvantages included problems involving privacy, because for many patients who were undergoing SUD recovery, it was impossible to be alone in a room or a designated area of their own.

The counselors also felt strongly that in-person care was needed for certain patients.

“Before COVID happened, [health care] barriers included transport to the actual center and finding care for children,” Ms. Connolly said in an interview.

“That’s where telehealth really bridged the gap for these people, and it actually became a lot easier for them to get in contact with their counselors, get into group meetings, and access other services,” she said.

Many of the study participants were not very optimistic about telehealth at first, Ms. Connolly noted. “They felt a little odd going on telehealth at first, but by the end, everybody said that they loved having it.”

“One of the things that came out often was that patients felt they could be more open and honest because they weren’t looking their counselor right in the face. They didn’t feel so horrible sharing,” Ms. Whiteside added.

Some counselors reported that some clients shared more details with them and that there was an ease of connecting. If a patient was a few minutes late to an appointment, telehealth would put in a call to find out where that patient was.

The counselors also had the ability to determine which of their patients would be good candidates for telehealth counseling and which patients would not do well with telehealth and would instead need in-patient care.

“This is something that really helped the experience go better for the counselors. They were able to determine which patient fit the mold for telehealth working for them. Obviously, patients who have more acute periods of mental health problems would do better with in-person care,” Ms. Whiteside said.
 

Here to stay?

In the third study from USCSM-G, investigators evaluated data from a focus group of four providers of medications for opioid use disorder (MOUD) who practiced in urban and rural areas throughout the state.

The respondents reflected on their experiences in using telemedicine for prescribing MOUD.

As in the previous studies, the providers had positive experiences with telemedicine. It increased patient access, participation, and satisfaction with treatment, and the benefits of telemedicine outweighed its potential limitations.

Still, technology was cited as a barrier to care, especially in rural areas.

“We found that there was a lack of good internet in certain rural parts of South Carolina, and that lack of the proper electronic devices ... could also make it difficult to access telemedicine,” lead author Kellie Shell said in an interview.

As noted in the other studies, the providers expressed a desire that telemedicine incorporate safeguards that would enable clinicians to identify a particular patient’s location in order that authorities could be dispatched if an emergency were to arise.

The clinicians also said that monitoring for diversion and performing pill counts were more difficult to do via telemedicine.

“We definitely have to improve infrastructure, especially in rural areas, so that all people have access to telemedicine,” Ms. Shell said.

“Overall, the providers were won over with telemedicine, and some predicted telehealth and virtual visits were here to stay, even after COVID,” she added.

The three posters provide useful insight into the potential advantages and disadvantages of telehealth in SUD settings, experts said.
 

Telehealth data ‘very limited’

Commenting on the research, Lewei (Allison) Lin, MD, University of Michigan, Ann Arbor, noted that “there is such limited information” about the use of telehealth for patients with SUD.

“These insights are helpful for us to start understanding the things that need to be considered, including clinician attitudes and perceptions,” said Dr. Lin, who was not involved with the studies.

“It will be key to have data as use of telemedicine increases during COVID-19 to help us see exactly how it should be used and to better understand the actual impacts and whether or not it is increasing accessibility, and for which patients,” she added.

David Kan, MD, chief medical officer at Bright Heart Health, San Ramon, Calif., has had experience with telehealth for SUD and has found that conducting pill counts with his patients has not been a problem.

“The Shell poster covers telemedicine well,” Dr. Kan said in an interview.

However, “I disagree with their point that diversion prevention is harder via telemedicine. In my experience, it is easier, as you can do pill or wrapper counts almost on demand. You can also do daily observed dosing with pill counts if diversion is suspected,” he said.

Dr. Kan also suggested ways to cope with problems involving privacy. “Privacy concerns are always an issue but can be mitigated with headphones and a scan of the room with the telehealth technology if a privacy concern arises.”

He acknowledged that in-person meetings, especially through well-established programs, such as Alcoholics Anonymous (AA), will always be important. But he pointed out that people are finding ways to meet safely and have in-person connections.

“The AA has been providing virtual recovery meetings long before COVID. The common complaint is the loss of fellowship associated with recovery groups. I don’t know of a way to get around this short of vaccines,” Dr. Kan said. However, “people have adapted impressively with masked outdoor meetings and other forms of safe gathering.”

The investigators, Dr. Lin, and Dr. Kan reported no relevant financial relationships.
 

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

On close evaluation of the picture on her chest, she has pale macules and patches surrounded by erythematous ill-defined patches consistent with nevus anemicus. She also has several brown macules and light brown patches on the neck suggestive of café au lait macules. The findings of the picture raise the suspicion for neurofibromatosis, and it was recommended for her to be evaluated in person.

She comes several days later to the clinic. The caretaker, who is her aunt, reports she does not know much of the girl’s medical history as she recently moved from South America to live with her. The girl is a very nice and pleasant 8-year-old. She reports noticing the spots on her chest for about a year and that they seem to get a little itchier and more noticeable when she is hot or when she is running. She also reports increasing headaches for several months. She is being home schooled, and according to her aunt she is at par with her cousins who are about the same age. There is no history of seizures. She has had back surgery in the past. There is no history of hypertension. There is no family history of any genetic disorder or similar lesions.

On physical exam, her vital signs are normal, but her head circumference is over the 90th percentile. She is pleasant and interactive. On skin examination, she has slightly noticeable pale macules and patches on the chest and back that become more apparent after rubbing her skin. She has multiple light brown macules and oval patches on the chest, back, and neck. She has no axillary or inguinal freckling. She has scars on the back from her prior surgery.

As she was having worsening headaches, an MRI of the brain was ordered, which showed a left optic glioma. She was then referred to ophthalmology, neurology, and genetics.

Neurofibromatosis type 1 (NF1) is a common genetic autosomal dominant disorder cause by mutations on the NF1 gene on chromosome 17, which encodes for the protein neurofibromin. This protein works in the Ras-mitogen–activated protein kinase pathway as a negative regulator. Based on the National Institute of Health criteria, children need two or more of the following to be diagnosed with NF1: more than six café au lait macules larger than 5 mm in prepubescent children and 2.5 cm after puberty; axillary or inguinal freckling; two or more Lisch nodules; optic gliomas; two or more neurofibromas or one plexiform neurofibroma; or a first degree relative with a diagnosis of NF1. With these criteria, about 70% of the children can be diagnosed before the age of 1 year.¹

Nevus anemicus is an uncommon birthmark, sometimes overlooked, that is characterized by pale, hypopigmented, well-defined macules and patches that do not turn red after trauma or changes in temperature. Nevus anemicus is usually localized on the torso but can be seen on the face, neck, and extremities. These lesions are present in 1%-2% of the general population. They are thought to occur because of increased sensitivity of the affected blood vessels to catecholamines, which causes permanent vasoconstriction, which leads to hypopigmentation on the area.² These lesions are usually present at birth and have been described in patients with tuberous sclerosis, neurofibromatosis, and phakomatosis pigmentovascularis.

Recent studies of patients with neurofibromatosis and other RASopathies have noticed that nevus anemicus is present in about 8.8%-51% of the patients studied with a diagnosis NF1, compared with only 2% of the controls.^3,4 The studies failed to report any cases of nevus anemicus in patients with other RASopathies associated with café au lait macules. Bulteel and colleagues recently reported two cases of non-NF1 RASopathies also associated with nevus anemicus in a patient with Legius syndrome and a patient with Noonan syndrome with multiple lentigines.⁵ The nevus anemicus was reported to occur most commonly on the anterior chest and be multiple, as seen in our patient.

The authors of the published studies advocate for the introduction of nevus anemicus as part of the diagnostic criteria for NF1, especially because it can be an early finding seen in babies, which can aid in early diagnosis of NF1.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She has no relevant financial disclosures. Email Dr. Matiz at [email protected].

References

1. Pediatrics. 2000 Mar. doi: 10.1542/peds.105.3.608.

2. Nevus Anemicus. StatPearls [Internet] (Treasure Island, Fla.: StatPearls Publishing; 2020 Jan).

3. J Am Acad Dermatol. 2013 Nov. doi: 10.1016/j.jaad.2013.06.039.

4. Pediatr Dermatol. 2015 May-Jun. doi: 10.1111/pde.12525.

5. JAAD Case Rep. 2018 Apr 5. doi: 10.1016/j.jdcr.2017.09.037.
 

On close evaluation of the picture on her chest, she has pale macules and patches surrounded by erythematous ill-defined patches consistent with nevus anemicus. She also has several brown macules and light brown patches on the neck suggestive of café au lait macules. The findings of the picture raise the suspicion for neurofibromatosis, and it was recommended for her to be evaluated in person.

She comes several days later to the clinic. The caretaker, who is her aunt, reports she does not know much of the girl’s medical history as she recently moved from South America to live with her. The girl is a very nice and pleasant 8-year-old. She reports noticing the spots on her chest for about a year and that they seem to get a little itchier and more noticeable when she is hot or when she is running. She also reports increasing headaches for several months. She is being home schooled, and according to her aunt she is at par with her cousins who are about the same age. There is no history of seizures. She has had back surgery in the past. There is no history of hypertension. There is no family history of any genetic disorder or similar lesions.

On physical exam, her vital signs are normal, but her head circumference is over the 90th percentile. She is pleasant and interactive. On skin examination, she has slightly noticeable pale macules and patches on the chest and back that become more apparent after rubbing her skin. She has multiple light brown macules and oval patches on the chest, back, and neck. She has no axillary or inguinal freckling. She has scars on the back from her prior surgery.

As she was having worsening headaches, an MRI of the brain was ordered, which showed a left optic glioma. She was then referred to ophthalmology, neurology, and genetics.

Neurofibromatosis type 1 (NF1) is a common genetic autosomal dominant disorder cause by mutations on the NF1 gene on chromosome 17, which encodes for the protein neurofibromin. This protein works in the Ras-mitogen–activated protein kinase pathway as a negative regulator. Based on the National Institute of Health criteria, children need two or more of the following to be diagnosed with NF1: more than six café au lait macules larger than 5 mm in prepubescent children and 2.5 cm after puberty; axillary or inguinal freckling; two or more Lisch nodules; optic gliomas; two or more neurofibromas or one plexiform neurofibroma; or a first degree relative with a diagnosis of NF1. With these criteria, about 70% of the children can be diagnosed before the age of 1 year.¹

Nevus anemicus is an uncommon birthmark, sometimes overlooked, that is characterized by pale, hypopigmented, well-defined macules and patches that do not turn red after trauma or changes in temperature. Nevus anemicus is usually localized on the torso but can be seen on the face, neck, and extremities. These lesions are present in 1%-2% of the general population. They are thought to occur because of increased sensitivity of the affected blood vessels to catecholamines, which causes permanent vasoconstriction, which leads to hypopigmentation on the area.² These lesions are usually present at birth and have been described in patients with tuberous sclerosis, neurofibromatosis, and phakomatosis pigmentovascularis.

Recent studies of patients with neurofibromatosis and other RASopathies have noticed that nevus anemicus is present in about 8.8%-51% of the patients studied with a diagnosis NF1, compared with only 2% of the controls.^3,4 The studies failed to report any cases of nevus anemicus in patients with other RASopathies associated with café au lait macules. Bulteel and colleagues recently reported two cases of non-NF1 RASopathies also associated with nevus anemicus in a patient with Legius syndrome and a patient with Noonan syndrome with multiple lentigines.⁵ The nevus anemicus was reported to occur most commonly on the anterior chest and be multiple, as seen in our patient.

The authors of the published studies advocate for the introduction of nevus anemicus as part of the diagnostic criteria for NF1, especially because it can be an early finding seen in babies, which can aid in early diagnosis of NF1.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She has no relevant financial disclosures. Email Dr. Matiz at [email protected].

References

1. Pediatrics. 2000 Mar. doi: 10.1542/peds.105.3.608.

2. Nevus Anemicus. StatPearls [Internet] (Treasure Island, Fla.: StatPearls Publishing; 2020 Jan).

3. J Am Acad Dermatol. 2013 Nov. doi: 10.1016/j.jaad.2013.06.039.

4. Pediatr Dermatol. 2015 May-Jun. doi: 10.1111/pde.12525.

5. JAAD Case Rep. 2018 Apr 5. doi: 10.1016/j.jdcr.2017.09.037.
 

On close evaluation of the picture on her chest, she has pale macules and patches surrounded by erythematous ill-defined patches consistent with nevus anemicus. She also has several brown macules and light brown patches on the neck suggestive of café au lait macules. The findings of the picture raise the suspicion for neurofibromatosis, and it was recommended for her to be evaluated in person.

She comes several days later to the clinic. The caretaker, who is her aunt, reports she does not know much of the girl’s medical history as she recently moved from South America to live with her. The girl is a very nice and pleasant 8-year-old. She reports noticing the spots on her chest for about a year and that they seem to get a little itchier and more noticeable when she is hot or when she is running. She also reports increasing headaches for several months. She is being home schooled, and according to her aunt she is at par with her cousins who are about the same age. There is no history of seizures. She has had back surgery in the past. There is no history of hypertension. There is no family history of any genetic disorder or similar lesions.

On physical exam, her vital signs are normal, but her head circumference is over the 90th percentile. She is pleasant and interactive. On skin examination, she has slightly noticeable pale macules and patches on the chest and back that become more apparent after rubbing her skin. She has multiple light brown macules and oval patches on the chest, back, and neck. She has no axillary or inguinal freckling. She has scars on the back from her prior surgery.

As she was having worsening headaches, an MRI of the brain was ordered, which showed a left optic glioma. She was then referred to ophthalmology, neurology, and genetics.

Neurofibromatosis type 1 (NF1) is a common genetic autosomal dominant disorder cause by mutations on the NF1 gene on chromosome 17, which encodes for the protein neurofibromin. This protein works in the Ras-mitogen–activated protein kinase pathway as a negative regulator. Based on the National Institute of Health criteria, children need two or more of the following to be diagnosed with NF1: more than six café au lait macules larger than 5 mm in prepubescent children and 2.5 cm after puberty; axillary or inguinal freckling; two or more Lisch nodules; optic gliomas; two or more neurofibromas or one plexiform neurofibroma; or a first degree relative with a diagnosis of NF1. With these criteria, about 70% of the children can be diagnosed before the age of 1 year.¹

Nevus anemicus is an uncommon birthmark, sometimes overlooked, that is characterized by pale, hypopigmented, well-defined macules and patches that do not turn red after trauma or changes in temperature. Nevus anemicus is usually localized on the torso but can be seen on the face, neck, and extremities. These lesions are present in 1%-2% of the general population. They are thought to occur because of increased sensitivity of the affected blood vessels to catecholamines, which causes permanent vasoconstriction, which leads to hypopigmentation on the area.² These lesions are usually present at birth and have been described in patients with tuberous sclerosis, neurofibromatosis, and phakomatosis pigmentovascularis.

Recent studies of patients with neurofibromatosis and other RASopathies have noticed that nevus anemicus is present in about 8.8%-51% of the patients studied with a diagnosis NF1, compared with only 2% of the controls.^3,4 The studies failed to report any cases of nevus anemicus in patients with other RASopathies associated with café au lait macules. Bulteel and colleagues recently reported two cases of non-NF1 RASopathies also associated with nevus anemicus in a patient with Legius syndrome and a patient with Noonan syndrome with multiple lentigines.⁵ The nevus anemicus was reported to occur most commonly on the anterior chest and be multiple, as seen in our patient.

The authors of the published studies advocate for the introduction of nevus anemicus as part of the diagnostic criteria for NF1, especially because it can be an early finding seen in babies, which can aid in early diagnosis of NF1.

Dr. Matiz is a pediatric dermatologist at Southern California Permanente Medical Group, San Diego. She has no relevant financial disclosures. Email Dr. Matiz at [email protected].

References

1. Pediatrics. 2000 Mar. doi: 10.1542/peds.105.3.608.

2. Nevus Anemicus. StatPearls [Internet] (Treasure Island, Fla.: StatPearls Publishing; 2020 Jan).

3. J Am Acad Dermatol. 2013 Nov. doi: 10.1016/j.jaad.2013.06.039.

4. Pediatr Dermatol. 2015 May-Jun. doi: 10.1111/pde.12525.

5. JAAD Case Rep. 2018 Apr 5. doi: 10.1016/j.jdcr.2017.09.037.
 

An investigational chimeric antigen receptor T-cell (CAR T-cell) construct targeting two antigens on multiple myeloma cells showed promise in a first-in-humans trial, investigators said.

Among 16 patients with relapsed/refractory, heavily pretreated multiple myeloma who received the dual-targeting construct GC012F, the overall response rate was 93.8%, and all of six patients who received the cells at the highest of three dose levels had stringent complete responses (sCR) and were negative for minimal residual disease (MRD) at 6 months follow-up, reported Weijun Fu, MD, PhD, from Shanghai (China) Changzheng Hospital in an oral abstract presented during the virtual American Society of Hematology annual meeting.

GC012F is a novel CAR-T cell platform targeting both the B-cell maturation antigen (BCMA), which is universally expressed on malignant plasma cells, and CD19, which is expressed on both multiple myeloma cells and progenitors, Dr. Fu said.

“Targeting CD19 can trigger elimination of malignant cells by CAR T. Our preclinical work demonstrated more effective elimination of multiple myeloma clone-forming cells by BCMA and CD19 dual CAR T, so targeting both BCMA and CD19 antigens could improve efficacy and reduce relapse,” he said.

The construct is created using the FasTCAR platform that, according to manufacturer Gracell Biotechnologies (Shanghai), allows for cell culturing and expansion within 24-36 hours, rather than 2-3 weeks required for other CAR T-cell products.
 

Investigator-initiated trial

In a phase 1 investigator-initiated trial, 16 patients with a median age of 56 (range 27-71) years were enrolled. The patients all had relapsed or refractory multiple myeloma according to 2016 International Myeloma Working Group criteria, with a life expectancy of at least 3 months and adequate organ function.

The median time since diagnosis was 3 years (range 1-10). All but one of the 16 patients had high-risk disease, 3 had double-hit disease (the presence of two deletions, gain of function, or p53 mutation), and 5 patients had one or more extramedullary plasmacytomas. Four of the patients had received therapy with an anti-CD38 monoclonal antibody.

Following lymphodepletion with fludarabine and cyclophosphamide, the patients received the CAR T cells in a single infusion at dose levels of either 1, 2, or 3 times 10⁵ cells/kg.

As of the cutoff date in July 2020, 15 of the 16 patients had a clinical response, including 9 with a CR or sCR, and 6 with a very good partial response (VGPR). As noted before, all of the six patients treated at the highest dose level had a sCR. At the median follow-up of 7.3 months, the median duration of response had not been reached.

Among all patients evaluable for response at month 1 (14 patients), 11 were MRD negative by flow cytometry. At month 3 all 11 evaluable patients were MRD negative, and all of 10 patients evaluable at 6 months were also MRD negative.

As with other CAR T-cell constructs, all patients developed the cytokine-release syndrome (CRS), with grade 1 or 2 severity in 14 patients, and grade 3 in 2 patients. The median time to onset of CRS was 6 days (range 2-10), and the median duration was 4 days (range 1-8 days).

No cases of immune effector cell–associated neurotoxicity syndrome (ICANS) were observed.

One patient treated at the middle dose level presented with fever and died shortly after day 78 of an unknown cause during the COVID-19 pandemic. Two patients died of extramedullary disease; each had achieved MRD negativity.

Investigators continue to follow the patients and are enrolling new patients in the ongoing study.
 

‘Interesting approach’

Sandy W. Wong, MD, from the Helen Diller Family Comprehensive Cancer Center at the University of California San Francisco, who was not involved in the study, said in an interview that the dual-targeted approach is interesting, in light of a case report presented at ASH 2020 of a patient with multiple myeloma who had a partial response to CAR T-cell therapy with a different construct and who developed a subsequent biallelic loss of BCMA that resulted in resistance to CAR T-cell therapy.

“This raises the idea that, if we perhaps had a dual-targeted CAR T, perhaps we will prolong progression-free survival, in order to avoid antigen escape. So I do think the concept is very interesting and does deserve further study,” she said.

CD19 is thought to be expressed on myeloma stem cells, “so the question is: Are patients not being cured because there is a reservoir of myeloma cells, and targeting CD19 is thought to get at this putative myeloma stem cell? but that remains to be seen,” she added.

Dr. Wong comoderated the session where Dr. Fu presented the data.

The study was supported by participating medical centers and Gracell Biotechnologies. Dr. Fu and Dr. Wong reported no relevant conflicts of interest to disclose.

SOURCE: Jiang H et al. ASH 2020, Abstract 178.

An investigational chimeric antigen receptor T-cell (CAR T-cell) construct targeting two antigens on multiple myeloma cells showed promise in a first-in-humans trial, investigators said.

Among 16 patients with relapsed/refractory, heavily pretreated multiple myeloma who received the dual-targeting construct GC012F, the overall response rate was 93.8%, and all of six patients who received the cells at the highest of three dose levels had stringent complete responses (sCR) and were negative for minimal residual disease (MRD) at 6 months follow-up, reported Weijun Fu, MD, PhD, from Shanghai (China) Changzheng Hospital in an oral abstract presented during the virtual American Society of Hematology annual meeting.

GC012F is a novel CAR-T cell platform targeting both the B-cell maturation antigen (BCMA), which is universally expressed on malignant plasma cells, and CD19, which is expressed on both multiple myeloma cells and progenitors, Dr. Fu said.

“Targeting CD19 can trigger elimination of malignant cells by CAR T. Our preclinical work demonstrated more effective elimination of multiple myeloma clone-forming cells by BCMA and CD19 dual CAR T, so targeting both BCMA and CD19 antigens could improve efficacy and reduce relapse,” he said.

The construct is created using the FasTCAR platform that, according to manufacturer Gracell Biotechnologies (Shanghai), allows for cell culturing and expansion within 24-36 hours, rather than 2-3 weeks required for other CAR T-cell products.
 

Investigator-initiated trial

In a phase 1 investigator-initiated trial, 16 patients with a median age of 56 (range 27-71) years were enrolled. The patients all had relapsed or refractory multiple myeloma according to 2016 International Myeloma Working Group criteria, with a life expectancy of at least 3 months and adequate organ function.

The median time since diagnosis was 3 years (range 1-10). All but one of the 16 patients had high-risk disease, 3 had double-hit disease (the presence of two deletions, gain of function, or p53 mutation), and 5 patients had one or more extramedullary plasmacytomas. Four of the patients had received therapy with an anti-CD38 monoclonal antibody.

Following lymphodepletion with fludarabine and cyclophosphamide, the patients received the CAR T cells in a single infusion at dose levels of either 1, 2, or 3 times 10⁵ cells/kg.

As of the cutoff date in July 2020, 15 of the 16 patients had a clinical response, including 9 with a CR or sCR, and 6 with a very good partial response (VGPR). As noted before, all of the six patients treated at the highest dose level had a sCR. At the median follow-up of 7.3 months, the median duration of response had not been reached.

Among all patients evaluable for response at month 1 (14 patients), 11 were MRD negative by flow cytometry. At month 3 all 11 evaluable patients were MRD negative, and all of 10 patients evaluable at 6 months were also MRD negative.

As with other CAR T-cell constructs, all patients developed the cytokine-release syndrome (CRS), with grade 1 or 2 severity in 14 patients, and grade 3 in 2 patients. The median time to onset of CRS was 6 days (range 2-10), and the median duration was 4 days (range 1-8 days).

No cases of immune effector cell–associated neurotoxicity syndrome (ICANS) were observed.

One patient treated at the middle dose level presented with fever and died shortly after day 78 of an unknown cause during the COVID-19 pandemic. Two patients died of extramedullary disease; each had achieved MRD negativity.

Investigators continue to follow the patients and are enrolling new patients in the ongoing study.
 

‘Interesting approach’

Sandy W. Wong, MD, from the Helen Diller Family Comprehensive Cancer Center at the University of California San Francisco, who was not involved in the study, said in an interview that the dual-targeted approach is interesting, in light of a case report presented at ASH 2020 of a patient with multiple myeloma who had a partial response to CAR T-cell therapy with a different construct and who developed a subsequent biallelic loss of BCMA that resulted in resistance to CAR T-cell therapy.

“This raises the idea that, if we perhaps had a dual-targeted CAR T, perhaps we will prolong progression-free survival, in order to avoid antigen escape. So I do think the concept is very interesting and does deserve further study,” she said.

CD19 is thought to be expressed on myeloma stem cells, “so the question is: Are patients not being cured because there is a reservoir of myeloma cells, and targeting CD19 is thought to get at this putative myeloma stem cell? but that remains to be seen,” she added.

Dr. Wong comoderated the session where Dr. Fu presented the data.

The study was supported by participating medical centers and Gracell Biotechnologies. Dr. Fu and Dr. Wong reported no relevant conflicts of interest to disclose.

SOURCE: Jiang H et al. ASH 2020, Abstract 178.

An investigational chimeric antigen receptor T-cell (CAR T-cell) construct targeting two antigens on multiple myeloma cells showed promise in a first-in-humans trial, investigators said.

Among 16 patients with relapsed/refractory, heavily pretreated multiple myeloma who received the dual-targeting construct GC012F, the overall response rate was 93.8%, and all of six patients who received the cells at the highest of three dose levels had stringent complete responses (sCR) and were negative for minimal residual disease (MRD) at 6 months follow-up, reported Weijun Fu, MD, PhD, from Shanghai (China) Changzheng Hospital in an oral abstract presented during the virtual American Society of Hematology annual meeting.

GC012F is a novel CAR-T cell platform targeting both the B-cell maturation antigen (BCMA), which is universally expressed on malignant plasma cells, and CD19, which is expressed on both multiple myeloma cells and progenitors, Dr. Fu said.

“Targeting CD19 can trigger elimination of malignant cells by CAR T. Our preclinical work demonstrated more effective elimination of multiple myeloma clone-forming cells by BCMA and CD19 dual CAR T, so targeting both BCMA and CD19 antigens could improve efficacy and reduce relapse,” he said.

The construct is created using the FasTCAR platform that, according to manufacturer Gracell Biotechnologies (Shanghai), allows for cell culturing and expansion within 24-36 hours, rather than 2-3 weeks required for other CAR T-cell products.
 

Investigator-initiated trial

In a phase 1 investigator-initiated trial, 16 patients with a median age of 56 (range 27-71) years were enrolled. The patients all had relapsed or refractory multiple myeloma according to 2016 International Myeloma Working Group criteria, with a life expectancy of at least 3 months and adequate organ function.

The median time since diagnosis was 3 years (range 1-10). All but one of the 16 patients had high-risk disease, 3 had double-hit disease (the presence of two deletions, gain of function, or p53 mutation), and 5 patients had one or more extramedullary plasmacytomas. Four of the patients had received therapy with an anti-CD38 monoclonal antibody.

Following lymphodepletion with fludarabine and cyclophosphamide, the patients received the CAR T cells in a single infusion at dose levels of either 1, 2, or 3 times 10⁵ cells/kg.

As of the cutoff date in July 2020, 15 of the 16 patients had a clinical response, including 9 with a CR or sCR, and 6 with a very good partial response (VGPR). As noted before, all of the six patients treated at the highest dose level had a sCR. At the median follow-up of 7.3 months, the median duration of response had not been reached.

Among all patients evaluable for response at month 1 (14 patients), 11 were MRD negative by flow cytometry. At month 3 all 11 evaluable patients were MRD negative, and all of 10 patients evaluable at 6 months were also MRD negative.

As with other CAR T-cell constructs, all patients developed the cytokine-release syndrome (CRS), with grade 1 or 2 severity in 14 patients, and grade 3 in 2 patients. The median time to onset of CRS was 6 days (range 2-10), and the median duration was 4 days (range 1-8 days).

No cases of immune effector cell–associated neurotoxicity syndrome (ICANS) were observed.

One patient treated at the middle dose level presented with fever and died shortly after day 78 of an unknown cause during the COVID-19 pandemic. Two patients died of extramedullary disease; each had achieved MRD negativity.

Investigators continue to follow the patients and are enrolling new patients in the ongoing study.
 

‘Interesting approach’

Sandy W. Wong, MD, from the Helen Diller Family Comprehensive Cancer Center at the University of California San Francisco, who was not involved in the study, said in an interview that the dual-targeted approach is interesting, in light of a case report presented at ASH 2020 of a patient with multiple myeloma who had a partial response to CAR T-cell therapy with a different construct and who developed a subsequent biallelic loss of BCMA that resulted in resistance to CAR T-cell therapy.

“This raises the idea that, if we perhaps had a dual-targeted CAR T, perhaps we will prolong progression-free survival, in order to avoid antigen escape. So I do think the concept is very interesting and does deserve further study,” she said.

CD19 is thought to be expressed on myeloma stem cells, “so the question is: Are patients not being cured because there is a reservoir of myeloma cells, and targeting CD19 is thought to get at this putative myeloma stem cell? but that remains to be seen,” she added.

Dr. Wong comoderated the session where Dr. Fu presented the data.

The study was supported by participating medical centers and Gracell Biotechnologies. Dr. Fu and Dr. Wong reported no relevant conflicts of interest to disclose.

SOURCE: Jiang H et al. ASH 2020, Abstract 178.