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CDC shortens COVID-19 quarantine time to 10 or 7 days, with conditions
Citing new evidence and an “acceptable risk” of transmission, the agency hopes reducing the 14-day quarantine will increase overall compliance and improve public health and economic constraints.
The agency also suggested people postpone travel during the upcoming winter holidays and stay home because of the pandemic.
These shorter quarantine options do not replace initial CDC guidance. “CDC continues to recommend quarantining for 14 days as the best way to reduce risk for spreading COVID-19,” said Henry Walke, MD, MPH, the CDC’s COVID-19 incident manager, during a media briefing on Wednesday.
However, “after reviewing and analyzing new research and data, CDC has identified two acceptable alternative quarantine periods.”
People can now quarantine for 10 days without a COVID-19 test if they have no symptoms. Alternatively, a quarantine can end after 7 days for someone with a negative test and no symptoms. The agency recommends a polymerase chain reaction test or an antigen assay within 48 hours before the end of a quarantine.
The agency also suggests people still monitor for symptoms for a full 14 days.
Reducing the length of quarantine “may make it easier for people to take this critical public health action, by reducing the economic hardship associated with a longer period, especially if they cannot work during that time,” Dr. Walke said. “In addition, a shorter quarantine period can lessen stress on the public health system and communities, especially when new infections are rapidly rising.”
The federal guidance leaves flexibility for local jurisdictions to make their own quarantine recommendations, as warranted, he added.
An ‘acceptable risk’ calculation
Modeling by the CDC and academic and public health partners led to the new quarantine recommendations, said John Brooks, MD, chief medical officer for the CDC’s COVID-19 response. Multiple studies “point in the same direction, which is that we can safely reduce the length of quarantine but accept there is a small residual risk that a person who is leaving quarantine early could transmit to someone else.”
The residual risk is approximately 1%, with an upper limit of 10%, when people quarantine for 10 days. A 7-day quarantine carries a residual risk of about 5% and an upper limit of 12%.
“Ten days is where the risk got into a sweet spot we like, at about 1%,” Dr. Brooks said. “That is a very acceptable risk, I think, for many people.”
Although it remains unknown what proportion of people spending 14 days in quarantine leave early, “we are hearing anecdotally from our partners in public health that many people are discontinuing quarantine ahead of time because there is pressure to go back to work, to get people back into school – and it imposes a burden on the individual,” Dr. Brooks said.
“One of our hopes is that ... if we reduce the amount of time they have to spend in quarantine, people will be more compliant,” he added.
A reporter asked why the CDC is shortening quarantines when the pandemic numbers are increasing nationwide. The timing has to do with capacity, Dr. Brooks said. “We are in situation where the number of cases is rising, the number of contacts is rising and the number of people who require quarantine is rising. That is a lot of burden, not just on the people who have to quarantine, but on public health.”
Home for the holidays
Similar to its pre-Thanksgiving advisory, the CDC also recommends people avoid travel during the upcoming winter holidays. “The best way to protect yourself and others is to postpone travel and stay home,” Dr. Walke said.
If people do decide to travel, the agency recommends COVID-19 testing 1-3 days prior to travel and again 3-5 days afterward, as well as reducing nonessential activities for a full 7 days after returning home. Furthermore, if someone does not have follow-up testing, the CDC recommends reducing nonessential activities for 10 days.
Testing does not eliminate all risk, Dr. Walke said, “but when combined with reducing nonessential activities, symptom screening and continuing with precautions like wearing masks, social distancing and hand washing, it can make travel safer.”
“We are trying to reduce the number of infections by postponing travel over the winter holiday,” Cindy Friedman, MD, chief of the CDC Travelers’ Health Branch, said during the media briefing.
“Travel volume was high during Thanksgiving,” she said, “and even if only a small percentage of those travelers were asymptomatically infected, this can translate into hundreds of thousands of additional infections moving from one community to another.”
This article first appeared on Medscape.com.
Citing new evidence and an “acceptable risk” of transmission, the agency hopes reducing the 14-day quarantine will increase overall compliance and improve public health and economic constraints.
The agency also suggested people postpone travel during the upcoming winter holidays and stay home because of the pandemic.
These shorter quarantine options do not replace initial CDC guidance. “CDC continues to recommend quarantining for 14 days as the best way to reduce risk for spreading COVID-19,” said Henry Walke, MD, MPH, the CDC’s COVID-19 incident manager, during a media briefing on Wednesday.
However, “after reviewing and analyzing new research and data, CDC has identified two acceptable alternative quarantine periods.”
People can now quarantine for 10 days without a COVID-19 test if they have no symptoms. Alternatively, a quarantine can end after 7 days for someone with a negative test and no symptoms. The agency recommends a polymerase chain reaction test or an antigen assay within 48 hours before the end of a quarantine.
The agency also suggests people still monitor for symptoms for a full 14 days.
Reducing the length of quarantine “may make it easier for people to take this critical public health action, by reducing the economic hardship associated with a longer period, especially if they cannot work during that time,” Dr. Walke said. “In addition, a shorter quarantine period can lessen stress on the public health system and communities, especially when new infections are rapidly rising.”
The federal guidance leaves flexibility for local jurisdictions to make their own quarantine recommendations, as warranted, he added.
An ‘acceptable risk’ calculation
Modeling by the CDC and academic and public health partners led to the new quarantine recommendations, said John Brooks, MD, chief medical officer for the CDC’s COVID-19 response. Multiple studies “point in the same direction, which is that we can safely reduce the length of quarantine but accept there is a small residual risk that a person who is leaving quarantine early could transmit to someone else.”
The residual risk is approximately 1%, with an upper limit of 10%, when people quarantine for 10 days. A 7-day quarantine carries a residual risk of about 5% and an upper limit of 12%.
“Ten days is where the risk got into a sweet spot we like, at about 1%,” Dr. Brooks said. “That is a very acceptable risk, I think, for many people.”
Although it remains unknown what proportion of people spending 14 days in quarantine leave early, “we are hearing anecdotally from our partners in public health that many people are discontinuing quarantine ahead of time because there is pressure to go back to work, to get people back into school – and it imposes a burden on the individual,” Dr. Brooks said.
“One of our hopes is that ... if we reduce the amount of time they have to spend in quarantine, people will be more compliant,” he added.
A reporter asked why the CDC is shortening quarantines when the pandemic numbers are increasing nationwide. The timing has to do with capacity, Dr. Brooks said. “We are in situation where the number of cases is rising, the number of contacts is rising and the number of people who require quarantine is rising. That is a lot of burden, not just on the people who have to quarantine, but on public health.”
Home for the holidays
Similar to its pre-Thanksgiving advisory, the CDC also recommends people avoid travel during the upcoming winter holidays. “The best way to protect yourself and others is to postpone travel and stay home,” Dr. Walke said.
If people do decide to travel, the agency recommends COVID-19 testing 1-3 days prior to travel and again 3-5 days afterward, as well as reducing nonessential activities for a full 7 days after returning home. Furthermore, if someone does not have follow-up testing, the CDC recommends reducing nonessential activities for 10 days.
Testing does not eliminate all risk, Dr. Walke said, “but when combined with reducing nonessential activities, symptom screening and continuing with precautions like wearing masks, social distancing and hand washing, it can make travel safer.”
“We are trying to reduce the number of infections by postponing travel over the winter holiday,” Cindy Friedman, MD, chief of the CDC Travelers’ Health Branch, said during the media briefing.
“Travel volume was high during Thanksgiving,” she said, “and even if only a small percentage of those travelers were asymptomatically infected, this can translate into hundreds of thousands of additional infections moving from one community to another.”
This article first appeared on Medscape.com.
Citing new evidence and an “acceptable risk” of transmission, the agency hopes reducing the 14-day quarantine will increase overall compliance and improve public health and economic constraints.
The agency also suggested people postpone travel during the upcoming winter holidays and stay home because of the pandemic.
These shorter quarantine options do not replace initial CDC guidance. “CDC continues to recommend quarantining for 14 days as the best way to reduce risk for spreading COVID-19,” said Henry Walke, MD, MPH, the CDC’s COVID-19 incident manager, during a media briefing on Wednesday.
However, “after reviewing and analyzing new research and data, CDC has identified two acceptable alternative quarantine periods.”
People can now quarantine for 10 days without a COVID-19 test if they have no symptoms. Alternatively, a quarantine can end after 7 days for someone with a negative test and no symptoms. The agency recommends a polymerase chain reaction test or an antigen assay within 48 hours before the end of a quarantine.
The agency also suggests people still monitor for symptoms for a full 14 days.
Reducing the length of quarantine “may make it easier for people to take this critical public health action, by reducing the economic hardship associated with a longer period, especially if they cannot work during that time,” Dr. Walke said. “In addition, a shorter quarantine period can lessen stress on the public health system and communities, especially when new infections are rapidly rising.”
The federal guidance leaves flexibility for local jurisdictions to make their own quarantine recommendations, as warranted, he added.
An ‘acceptable risk’ calculation
Modeling by the CDC and academic and public health partners led to the new quarantine recommendations, said John Brooks, MD, chief medical officer for the CDC’s COVID-19 response. Multiple studies “point in the same direction, which is that we can safely reduce the length of quarantine but accept there is a small residual risk that a person who is leaving quarantine early could transmit to someone else.”
The residual risk is approximately 1%, with an upper limit of 10%, when people quarantine for 10 days. A 7-day quarantine carries a residual risk of about 5% and an upper limit of 12%.
“Ten days is where the risk got into a sweet spot we like, at about 1%,” Dr. Brooks said. “That is a very acceptable risk, I think, for many people.”
Although it remains unknown what proportion of people spending 14 days in quarantine leave early, “we are hearing anecdotally from our partners in public health that many people are discontinuing quarantine ahead of time because there is pressure to go back to work, to get people back into school – and it imposes a burden on the individual,” Dr. Brooks said.
“One of our hopes is that ... if we reduce the amount of time they have to spend in quarantine, people will be more compliant,” he added.
A reporter asked why the CDC is shortening quarantines when the pandemic numbers are increasing nationwide. The timing has to do with capacity, Dr. Brooks said. “We are in situation where the number of cases is rising, the number of contacts is rising and the number of people who require quarantine is rising. That is a lot of burden, not just on the people who have to quarantine, but on public health.”
Home for the holidays
Similar to its pre-Thanksgiving advisory, the CDC also recommends people avoid travel during the upcoming winter holidays. “The best way to protect yourself and others is to postpone travel and stay home,” Dr. Walke said.
If people do decide to travel, the agency recommends COVID-19 testing 1-3 days prior to travel and again 3-5 days afterward, as well as reducing nonessential activities for a full 7 days after returning home. Furthermore, if someone does not have follow-up testing, the CDC recommends reducing nonessential activities for 10 days.
Testing does not eliminate all risk, Dr. Walke said, “but when combined with reducing nonessential activities, symptom screening and continuing with precautions like wearing masks, social distancing and hand washing, it can make travel safer.”
“We are trying to reduce the number of infections by postponing travel over the winter holiday,” Cindy Friedman, MD, chief of the CDC Travelers’ Health Branch, said during the media briefing.
“Travel volume was high during Thanksgiving,” she said, “and even if only a small percentage of those travelers were asymptomatically infected, this can translate into hundreds of thousands of additional infections moving from one community to another.”
This article first appeared on Medscape.com.
ACIP: Health workers, long-term care residents first tier for COVID-19 vaccine
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 that both groups be in the highest-priority group for vaccination. As such, ACIP recommends that both be included in phase 1a of the committee’s allocation plan.
The recommendation now goes to CDC director Robert Redfield, MD, for approval. State health departments are expected to rely on the recommendation, but ultimately can make their own decisions on how to allocate vaccine in their states.
“We hope that this vote gets us all one step closer to the day when we can all feel safe again and when this pandemic is over,” said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, at today’s meeting.
Health care workers are defined as paid and unpaid individuals serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care. Phase 1a would not include children who live in such facilities.
“Our goal in phase 1a with regard to health care personnel is to preserve the workforce and health care capacity regardless of where exposure occurs,” said ACIP panelist Grace Lee, MD, MPH, professor of paediatrics at Stanford (Calif.) University. Thus vaccination would cover clinical support staff, such as nursing assistants, environmental services staff, and food support staff.
“It is crucial to maintain our health care capacity,” said ACIP member Sharon Frey, MD, clinical director at the Center for Vaccine Development at Saint Louis University. “But it’s also important to prevent severe disease and death in the group that is at highest risk of those complications and that includes those in long-term care facilities.”
CDC staff said that staff and residents in those facilities account for 6% of COVID-19 cases and 40% of deaths.
But Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., voted against putting long-term care residents into the 1a phase. “We have traditionally tried a vaccine in a young healthy population and then hope it works in our frail older adults. So we enter this realm of ‘we hope it works and that it’s safe,’ and that concerns me on many levels particularly for this vaccine,” she said, noting that the vaccines closest to FDA authorization have not been studied in elderly adults who live in nursing homes or assisted living facilities.
She added: “I have no reservations for health care workers taking this vaccine.”
Prioritization could change
The phase 1a allocation fits within the “four ethical principles” outlined by ACIP and CDC staff Nov. 23: to maximize benefits and minimize harms, promote justice, mitigate health inequities, and promote transparency.
“My vote reflects maximum benefit, minimum harm, promoting justice and mitigating the health inequalities that exist with regard to distribution of this vaccine,” said ACIP Chair Jose Romero, MD. Romero, chief medical officer of the Arkansas Department of Health, voted in favor of the phase 1a plan.
He and other panelists noted, however, that allocation priorities could change after the FDA reviews and authorizes a vaccine.
The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet December 10 to review the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). The companies filed for emergency use on November 20.
A second vaccine, made by Moderna, is not far behind. The company reported on Nov. 30 that its messenger RNA vaccine was 94.1% effective and filed for emergency use the same day. The FDA’s VRBPAC will review the safety and efficacy data for the Moderna vaccine on Dec. 17.
“If individual vaccines receive emergency use authorization, we will have more data to consider, and that could lead to revision of our prioritization,” said ACIP member Robert Atmar, MD, John S. Dunn Research Foundation Clinical Professor in Infectious Diseases at Baylor College of Medicine, Houston.
ACIP will meet again after the Dec. 10 FDA advisory panel. But it won’t recommend a product until after the FDA has authorized it, said Amanda Cohn, MD, senior advisor for vaccines at the CDC’s National Center for Immunization and Respiratory Diseases.
Staggered immunization subprioritization urged
The CDC staff said that given the potential that not enough vaccine will be available immediately, it was recommending that health care organizations plan on creating a hierarchy of prioritization within institutions. And, they also urged staggering vaccination for personnel in similar units or positions, citing potential systemic or other reactions among health care workers.
“Consider planning for personnel to have time away from clinical care if health care personnel experience systemic symptoms post vaccination,” said Sarah Oliver, MD, MSPH, from the CDC.
The CDC will soon be issuing guidance on how to handle systemic symptoms with health care workers, Dr. Oliver noted.
Some 40 million doses of the Pfizer/BioNTech and Moderna vaccines are expected to be available by the end of December, with 5 million to 10 million a week coming online after that, Dr. Cohn said. That means not all health care workers will be vaccinated immediately. That may require “subprioritization, but for a limited period of time,” she said.
Dr. Messonnier said that, even with limited supplies, most of the states have told the CDC that they think they can vaccinate all of their health care workers within 3 weeks – some in less time.
The ACIP allocation plan is similar to but not exactly the same as that issued by the National Academy of Sciences, Engineering, and Medicine, which issued recommendations in October. That organization said that health care workers, first responders, older Americans living in congregate settings, and people with underlying health conditions should be the first to receive a vaccine.
ACIP has said that phase 1b would include essential workers, including police officers and firefighters, and those in education, transportation, and food and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years or older.
This article first appeared on Medscape.com.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 that both groups be in the highest-priority group for vaccination. As such, ACIP recommends that both be included in phase 1a of the committee’s allocation plan.
The recommendation now goes to CDC director Robert Redfield, MD, for approval. State health departments are expected to rely on the recommendation, but ultimately can make their own decisions on how to allocate vaccine in their states.
“We hope that this vote gets us all one step closer to the day when we can all feel safe again and when this pandemic is over,” said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, at today’s meeting.
Health care workers are defined as paid and unpaid individuals serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care. Phase 1a would not include children who live in such facilities.
“Our goal in phase 1a with regard to health care personnel is to preserve the workforce and health care capacity regardless of where exposure occurs,” said ACIP panelist Grace Lee, MD, MPH, professor of paediatrics at Stanford (Calif.) University. Thus vaccination would cover clinical support staff, such as nursing assistants, environmental services staff, and food support staff.
“It is crucial to maintain our health care capacity,” said ACIP member Sharon Frey, MD, clinical director at the Center for Vaccine Development at Saint Louis University. “But it’s also important to prevent severe disease and death in the group that is at highest risk of those complications and that includes those in long-term care facilities.”
CDC staff said that staff and residents in those facilities account for 6% of COVID-19 cases and 40% of deaths.
But Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., voted against putting long-term care residents into the 1a phase. “We have traditionally tried a vaccine in a young healthy population and then hope it works in our frail older adults. So we enter this realm of ‘we hope it works and that it’s safe,’ and that concerns me on many levels particularly for this vaccine,” she said, noting that the vaccines closest to FDA authorization have not been studied in elderly adults who live in nursing homes or assisted living facilities.
She added: “I have no reservations for health care workers taking this vaccine.”
Prioritization could change
The phase 1a allocation fits within the “four ethical principles” outlined by ACIP and CDC staff Nov. 23: to maximize benefits and minimize harms, promote justice, mitigate health inequities, and promote transparency.
“My vote reflects maximum benefit, minimum harm, promoting justice and mitigating the health inequalities that exist with regard to distribution of this vaccine,” said ACIP Chair Jose Romero, MD. Romero, chief medical officer of the Arkansas Department of Health, voted in favor of the phase 1a plan.
He and other panelists noted, however, that allocation priorities could change after the FDA reviews and authorizes a vaccine.
The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet December 10 to review the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). The companies filed for emergency use on November 20.
A second vaccine, made by Moderna, is not far behind. The company reported on Nov. 30 that its messenger RNA vaccine was 94.1% effective and filed for emergency use the same day. The FDA’s VRBPAC will review the safety and efficacy data for the Moderna vaccine on Dec. 17.
“If individual vaccines receive emergency use authorization, we will have more data to consider, and that could lead to revision of our prioritization,” said ACIP member Robert Atmar, MD, John S. Dunn Research Foundation Clinical Professor in Infectious Diseases at Baylor College of Medicine, Houston.
ACIP will meet again after the Dec. 10 FDA advisory panel. But it won’t recommend a product until after the FDA has authorized it, said Amanda Cohn, MD, senior advisor for vaccines at the CDC’s National Center for Immunization and Respiratory Diseases.
Staggered immunization subprioritization urged
The CDC staff said that given the potential that not enough vaccine will be available immediately, it was recommending that health care organizations plan on creating a hierarchy of prioritization within institutions. And, they also urged staggering vaccination for personnel in similar units or positions, citing potential systemic or other reactions among health care workers.
“Consider planning for personnel to have time away from clinical care if health care personnel experience systemic symptoms post vaccination,” said Sarah Oliver, MD, MSPH, from the CDC.
The CDC will soon be issuing guidance on how to handle systemic symptoms with health care workers, Dr. Oliver noted.
Some 40 million doses of the Pfizer/BioNTech and Moderna vaccines are expected to be available by the end of December, with 5 million to 10 million a week coming online after that, Dr. Cohn said. That means not all health care workers will be vaccinated immediately. That may require “subprioritization, but for a limited period of time,” she said.
Dr. Messonnier said that, even with limited supplies, most of the states have told the CDC that they think they can vaccinate all of their health care workers within 3 weeks – some in less time.
The ACIP allocation plan is similar to but not exactly the same as that issued by the National Academy of Sciences, Engineering, and Medicine, which issued recommendations in October. That organization said that health care workers, first responders, older Americans living in congregate settings, and people with underlying health conditions should be the first to receive a vaccine.
ACIP has said that phase 1b would include essential workers, including police officers and firefighters, and those in education, transportation, and food and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years or older.
This article first appeared on Medscape.com.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted 13-1 that both groups be in the highest-priority group for vaccination. As such, ACIP recommends that both be included in phase 1a of the committee’s allocation plan.
The recommendation now goes to CDC director Robert Redfield, MD, for approval. State health departments are expected to rely on the recommendation, but ultimately can make their own decisions on how to allocate vaccine in their states.
“We hope that this vote gets us all one step closer to the day when we can all feel safe again and when this pandemic is over,” said Nancy Messonnier, MD, director of the CDC’s National Center for Immunization and Respiratory Diseases, at today’s meeting.
Health care workers are defined as paid and unpaid individuals serving in health care settings who have the potential for direct or indirect exposure to patients or infectious materials. Long-term care residents are defined as adults who reside in facilities that provide a variety of services, including medical and personal care. Phase 1a would not include children who live in such facilities.
“Our goal in phase 1a with regard to health care personnel is to preserve the workforce and health care capacity regardless of where exposure occurs,” said ACIP panelist Grace Lee, MD, MPH, professor of paediatrics at Stanford (Calif.) University. Thus vaccination would cover clinical support staff, such as nursing assistants, environmental services staff, and food support staff.
“It is crucial to maintain our health care capacity,” said ACIP member Sharon Frey, MD, clinical director at the Center for Vaccine Development at Saint Louis University. “But it’s also important to prevent severe disease and death in the group that is at highest risk of those complications and that includes those in long-term care facilities.”
CDC staff said that staff and residents in those facilities account for 6% of COVID-19 cases and 40% of deaths.
But Helen Keipp Talbot, MD, associate professor of medicine at Vanderbilt University, Nashville, Tenn., voted against putting long-term care residents into the 1a phase. “We have traditionally tried a vaccine in a young healthy population and then hope it works in our frail older adults. So we enter this realm of ‘we hope it works and that it’s safe,’ and that concerns me on many levels particularly for this vaccine,” she said, noting that the vaccines closest to FDA authorization have not been studied in elderly adults who live in nursing homes or assisted living facilities.
She added: “I have no reservations for health care workers taking this vaccine.”
Prioritization could change
The phase 1a allocation fits within the “four ethical principles” outlined by ACIP and CDC staff Nov. 23: to maximize benefits and minimize harms, promote justice, mitigate health inequities, and promote transparency.
“My vote reflects maximum benefit, minimum harm, promoting justice and mitigating the health inequalities that exist with regard to distribution of this vaccine,” said ACIP Chair Jose Romero, MD. Romero, chief medical officer of the Arkansas Department of Health, voted in favor of the phase 1a plan.
He and other panelists noted, however, that allocation priorities could change after the FDA reviews and authorizes a vaccine.
The FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet December 10 to review the Pfizer/BioNTech’s messenger RNA-based vaccine (BNT162b2). The companies filed for emergency use on November 20.
A second vaccine, made by Moderna, is not far behind. The company reported on Nov. 30 that its messenger RNA vaccine was 94.1% effective and filed for emergency use the same day. The FDA’s VRBPAC will review the safety and efficacy data for the Moderna vaccine on Dec. 17.
“If individual vaccines receive emergency use authorization, we will have more data to consider, and that could lead to revision of our prioritization,” said ACIP member Robert Atmar, MD, John S. Dunn Research Foundation Clinical Professor in Infectious Diseases at Baylor College of Medicine, Houston.
ACIP will meet again after the Dec. 10 FDA advisory panel. But it won’t recommend a product until after the FDA has authorized it, said Amanda Cohn, MD, senior advisor for vaccines at the CDC’s National Center for Immunization and Respiratory Diseases.
Staggered immunization subprioritization urged
The CDC staff said that given the potential that not enough vaccine will be available immediately, it was recommending that health care organizations plan on creating a hierarchy of prioritization within institutions. And, they also urged staggering vaccination for personnel in similar units or positions, citing potential systemic or other reactions among health care workers.
“Consider planning for personnel to have time away from clinical care if health care personnel experience systemic symptoms post vaccination,” said Sarah Oliver, MD, MSPH, from the CDC.
The CDC will soon be issuing guidance on how to handle systemic symptoms with health care workers, Dr. Oliver noted.
Some 40 million doses of the Pfizer/BioNTech and Moderna vaccines are expected to be available by the end of December, with 5 million to 10 million a week coming online after that, Dr. Cohn said. That means not all health care workers will be vaccinated immediately. That may require “subprioritization, but for a limited period of time,” she said.
Dr. Messonnier said that, even with limited supplies, most of the states have told the CDC that they think they can vaccinate all of their health care workers within 3 weeks – some in less time.
The ACIP allocation plan is similar to but not exactly the same as that issued by the National Academy of Sciences, Engineering, and Medicine, which issued recommendations in October. That organization said that health care workers, first responders, older Americans living in congregate settings, and people with underlying health conditions should be the first to receive a vaccine.
ACIP has said that phase 1b would include essential workers, including police officers and firefighters, and those in education, transportation, and food and agriculture sectors. Phase 1c would include adults with high-risk medical conditions and those aged 65 years or older.
This article first appeared on Medscape.com.
What to do when anticoagulation fails cancer patients
When a patient with cancer develops venous thromboembolism despite anticoagulation, how to help them comes down to clinical judgment, according to hematologist Neil Zakai, MD, associate professor at the University of Vermont, Burlington.
“Unfortunately,” when it comes to “anticoagulation failure, we are entering an evidence free-zone,” with no large trials to guide management and only a few guiding principles, he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.
The first thing is to check if there was an inciting incident, such as medical noncompliance, an infection, or an interruption of anticoagulation. Dr. Zakai said he’s even had cancer patients develop heparin-induced thrombocytopenia when switched to enoxaparin from a direct oral anticoagulants (DOAC) for a procedure.
Once the underlying problem is addressed, patients may be able to continue with their original anticoagulant.
However, cancer progression is the main reason anticoagulation fails. “In general, it is very difficult to control cancer thrombosis if you can’t control cancer progression,” Dr. Zakai said.
In those cases, he steps up anticoagulation. Prophylactic dosing is increased to full treatment dosing, and patients on a DOAC are generally switched to a low molecular weight heparin (LMWH).
If patients are already on LMWH once daily, they will be bumped up to twice daily dosing; for instance, enoxaparin 1 mg/kg b.i.d. instead of 1.5 mg/kg q.d. Dr. Zakai said he’s gone as high at 2 or even 2.5 mg/kg to control thrombosis, without excessive bleeding.
In general, anticoagulation for thrombosis prophylaxis continues as long as the cancer is active, and certainly while patients are on hormonal treatments such as tamoxifen, which increases the risk.
Dr. Zakai stressed that both thrombosis and bleeding risk change for cancer patients over time, and treatment needs to keep up.
“I continuously assess the risk and benefit of anticoagulation. At certain times” such as during and for a few months after hospitalization, thrombosis risk increases; at other times, bleeding risk is higher. “You need to actively change your anticoagulation during those periods,” and tailor therapy based on transient risk factors. “People with cancer have peaks and troughs for their risk that we don’t take advantage of,” he said.
Dr. Zakai generally favors apixaban or enoxaparin for prophylaxis, carefully monitoring patients for bleeding and, for the DOAC, drug interactions with antiemetics, dexamethasone, and certain chemotherapy drugs.
He noted a recent trial that found a 59% reduction in venous thromboembolism risk in ambulatory cancer patients with apixaban 2.5 mg twice daily over 6 months, versus placebo, and a 6% absolute reduction, but at the cost of a twofold increase in bleeding risk, with an absolute 1.7% increase.
Dr. Zakai cautioned that patients in trials are selected for higher VTE and lower bleeding risks, so outcomes might “poorly reflect real world populations.” Dr. Zakai did not have any industry disclosures. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
When a patient with cancer develops venous thromboembolism despite anticoagulation, how to help them comes down to clinical judgment, according to hematologist Neil Zakai, MD, associate professor at the University of Vermont, Burlington.
“Unfortunately,” when it comes to “anticoagulation failure, we are entering an evidence free-zone,” with no large trials to guide management and only a few guiding principles, he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.
The first thing is to check if there was an inciting incident, such as medical noncompliance, an infection, or an interruption of anticoagulation. Dr. Zakai said he’s even had cancer patients develop heparin-induced thrombocytopenia when switched to enoxaparin from a direct oral anticoagulants (DOAC) for a procedure.
Once the underlying problem is addressed, patients may be able to continue with their original anticoagulant.
However, cancer progression is the main reason anticoagulation fails. “In general, it is very difficult to control cancer thrombosis if you can’t control cancer progression,” Dr. Zakai said.
In those cases, he steps up anticoagulation. Prophylactic dosing is increased to full treatment dosing, and patients on a DOAC are generally switched to a low molecular weight heparin (LMWH).
If patients are already on LMWH once daily, they will be bumped up to twice daily dosing; for instance, enoxaparin 1 mg/kg b.i.d. instead of 1.5 mg/kg q.d. Dr. Zakai said he’s gone as high at 2 or even 2.5 mg/kg to control thrombosis, without excessive bleeding.
In general, anticoagulation for thrombosis prophylaxis continues as long as the cancer is active, and certainly while patients are on hormonal treatments such as tamoxifen, which increases the risk.
Dr. Zakai stressed that both thrombosis and bleeding risk change for cancer patients over time, and treatment needs to keep up.
“I continuously assess the risk and benefit of anticoagulation. At certain times” such as during and for a few months after hospitalization, thrombosis risk increases; at other times, bleeding risk is higher. “You need to actively change your anticoagulation during those periods,” and tailor therapy based on transient risk factors. “People with cancer have peaks and troughs for their risk that we don’t take advantage of,” he said.
Dr. Zakai generally favors apixaban or enoxaparin for prophylaxis, carefully monitoring patients for bleeding and, for the DOAC, drug interactions with antiemetics, dexamethasone, and certain chemotherapy drugs.
He noted a recent trial that found a 59% reduction in venous thromboembolism risk in ambulatory cancer patients with apixaban 2.5 mg twice daily over 6 months, versus placebo, and a 6% absolute reduction, but at the cost of a twofold increase in bleeding risk, with an absolute 1.7% increase.
Dr. Zakai cautioned that patients in trials are selected for higher VTE and lower bleeding risks, so outcomes might “poorly reflect real world populations.” Dr. Zakai did not have any industry disclosures. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
When a patient with cancer develops venous thromboembolism despite anticoagulation, how to help them comes down to clinical judgment, according to hematologist Neil Zakai, MD, associate professor at the University of Vermont, Burlington.
“Unfortunately,” when it comes to “anticoagulation failure, we are entering an evidence free-zone,” with no large trials to guide management and only a few guiding principles, he said during his presentation at the 2020 Update in Nonneoplastic Hematology virtual conference.
The first thing is to check if there was an inciting incident, such as medical noncompliance, an infection, or an interruption of anticoagulation. Dr. Zakai said he’s even had cancer patients develop heparin-induced thrombocytopenia when switched to enoxaparin from a direct oral anticoagulants (DOAC) for a procedure.
Once the underlying problem is addressed, patients may be able to continue with their original anticoagulant.
However, cancer progression is the main reason anticoagulation fails. “In general, it is very difficult to control cancer thrombosis if you can’t control cancer progression,” Dr. Zakai said.
In those cases, he steps up anticoagulation. Prophylactic dosing is increased to full treatment dosing, and patients on a DOAC are generally switched to a low molecular weight heparin (LMWH).
If patients are already on LMWH once daily, they will be bumped up to twice daily dosing; for instance, enoxaparin 1 mg/kg b.i.d. instead of 1.5 mg/kg q.d. Dr. Zakai said he’s gone as high at 2 or even 2.5 mg/kg to control thrombosis, without excessive bleeding.
In general, anticoagulation for thrombosis prophylaxis continues as long as the cancer is active, and certainly while patients are on hormonal treatments such as tamoxifen, which increases the risk.
Dr. Zakai stressed that both thrombosis and bleeding risk change for cancer patients over time, and treatment needs to keep up.
“I continuously assess the risk and benefit of anticoagulation. At certain times” such as during and for a few months after hospitalization, thrombosis risk increases; at other times, bleeding risk is higher. “You need to actively change your anticoagulation during those periods,” and tailor therapy based on transient risk factors. “People with cancer have peaks and troughs for their risk that we don’t take advantage of,” he said.
Dr. Zakai generally favors apixaban or enoxaparin for prophylaxis, carefully monitoring patients for bleeding and, for the DOAC, drug interactions with antiemetics, dexamethasone, and certain chemotherapy drugs.
He noted a recent trial that found a 59% reduction in venous thromboembolism risk in ambulatory cancer patients with apixaban 2.5 mg twice daily over 6 months, versus placebo, and a 6% absolute reduction, but at the cost of a twofold increase in bleeding risk, with an absolute 1.7% increase.
Dr. Zakai cautioned that patients in trials are selected for higher VTE and lower bleeding risks, so outcomes might “poorly reflect real world populations.” Dr. Zakai did not have any industry disclosures. The conference was sponsored by MedscapeLive. MedscapeLive and this news organization are owned by the same parent company.
FROM 2020 UNNH
Practice-changing data at this year’s ASH meeting
Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.
Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.
This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
Ruxolitinib in chronic GvHD
“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.
In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.
One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.
“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”
There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).
“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.
Transplants for older patients with MDS
Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.
New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.
It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
Subcutaneous daratumumab
New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.
Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.
“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”
Negative data with tranexamic acid
The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.
“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
‘Very exciting’ news about gene therapy
Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.
In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.
Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”
Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.
“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”
He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.
This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”
New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).
At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.
“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
Race and bloods cancers
ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).
It found that “self-reported race was the best indicator of survival,” noted Lee.
Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.
Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.
Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.
A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?”
COVID-19 and blood disorders
Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.
An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.
“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.
“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
‘Fireside chat’ with Fauci
COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
“This will be kicking off our meeting on Saturday morning,” said Lee.
This article first appeared on Medscape.com.
Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.
Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.
This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
Ruxolitinib in chronic GvHD
“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.
In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.
One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.
“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”
There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).
“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.
Transplants for older patients with MDS
Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.
New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.
It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
Subcutaneous daratumumab
New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.
Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.
“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”
Negative data with tranexamic acid
The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.
“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
‘Very exciting’ news about gene therapy
Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.
In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.
Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”
Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.
“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”
He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.
This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”
New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).
At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.
“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
Race and bloods cancers
ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).
It found that “self-reported race was the best indicator of survival,” noted Lee.
Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.
Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.
Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.
A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?”
COVID-19 and blood disorders
Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.
An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.
“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.
“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
‘Fireside chat’ with Fauci
COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
“This will be kicking off our meeting on Saturday morning,” said Lee.
This article first appeared on Medscape.com.
Instead of flying out to San Diego in California and soaking up a bit of sunshine in between listening to new research presentations, hematologists from around the world will be glued to their computer screens next weekend, tuning into the 62nd American Society of Hematology annual meeting.
Like many other conferences this year, the ASH meeting will be virtual because of the continuing COVID-19 pandemic, although the dates remain the same: Dec. 5-8.
This is the premier hematology event of the year, and the largest hematology conference in the world, with around 3,500 abstracts presented this year, commented Aaron T. Gerds, MD, chair of ASH’s Committee on Communications.
Ruxolitinib in chronic GvHD
“One of the things that people come to ASH for is to hear about practice-changing clinical trials, and this year is no exception,” said ASH secretary Robert Brodsky, MD.
In a preview webinar, he highlighted four abstracts that offer opportunities to change practice and revamp the current standards of care.
One clinical trial that is “almost certainly a practice changer,” he said, is the REACH 3 study (abstract 77) of the JAK inhibitor ruxolitinib (Jakafi, Incyte) in patients with chronic graft-versus-host disease (GvHD) after a stem cell transplant.
“This has been really hard to treat in patients undergoing allogeneic bone marrow transplants,” said Brodsky. “Steroids are the first-line treatment, but after that, nothing else has shown any improvement, and even steroids don’t work that well.”
There is currently no approved second-line therapy for chronic forms of GvHD, he emphasized. The main endpoint of the trial was overall response rate, which was doubled with ruxolitinib compared to the best available therapy (50% vs 25%).
“This is the first successful phase 3 trial for chronic GvHD,” Brodsky commented.
Transplants for older patients with MDS
Transplant offers the only curative option for myelodysplastic syndromes (MDS), but typically this option is offered to younger patients because benefits for older adults have not been well-defined, Brodsky noted.
New data from a clinical trial conducted in patients with advanced MDS aged 50-75 years (abstract 75) offers the most definitive evidence to date that allogeneic hematopoietic cell transplantation (AHCT) can significantly improve outcomes for older adults.
It’s clear that transplant is the standard of care in younger patients, Brodsky commented, and although there is a trend of offering it to older patients, some are not getting referred and instead are being offered palliative care. “The thinking is that bone marrow transplant would be too toxic in this age group,” he said. “But what is very clear here is that, in an intent-to-treat analysis, there was a significant survival advantage – 48% versus 27% at 3 years for transplantation – and it was seen across all subgroups.”
Subcutaneous daratumumab
New data on a subcutaneous formulation of daratumumab (Darzalex, Janssen), which is usually given by intravenous infusion, will be presented from the APOLLO trial (abstract 412) in patients with relapsed/refractory multiple myeloma.
Patients who received subcutaneous daratumumab combined with pomalidomide and dexamethasone had a 37% reduction in disease progression or death compared to those who received pomalidomide and dexamethasone alone.
“From previous years we’ve learned that daratumumab has had a major impact on outcomes in multiple myeloma,” said Brodsky. “The nice thing about the subcutaneous formulation is that it can be administered quickly and in an outpatient setting, which is especially important in the COVID era.”
Negative data with tranexamic acid
The fourth abstract highlighted by Brodsky is a negative study, but its findings can help guide clinical practice, he said. The a-TREAT study (abstract 2) showed that, despite being routinely used in the clinical setting, tranexamic acid does not prevent bleeding when administered prophylactically to severely thrombocytopenic patients undergoing treatment for hematologic malignancies.
“They found absolutely no difference in bleeding or need for transfusion,” said Brodsky. “What they did find was more catheter-associated blood clots in the tranexamic acid group. This is a practice changer in that it probably should not be given prophylactically to patients with thrombocytopenia.”
‘Very exciting’ news about gene therapy
Brodsky also highlighted several late-breaking abstract that will be presented at the meeting.
In particular, the first data on a gene therapy for hemophilia B (abstract LBA-6) are “very, very exciting,” he said. The HOPE-B trial showed a 96% response rate among patients with hemophilia B who were treated with etranacogene dezaparvovec, an investigational gene therapy composed of an adeno-associated virus serotype 5 (AAV5) vector containing a codon-optimized Padua variant human factor IX.
Brodsky pointed out that this was a large trial with 54 patients, but importantly, it included patients with pre-existing anti-AAV5 neutralizing antibodies. “About 40% of patients have naturally occurring antibodies to AAV5, and they have been excluded from previous trials because it was thought they wouldn’t take the vector,” said Brodsky. “But only one patient didn’t get a response.”
Following a single dose of etranacogene dezaparvovec, Factor IX activity increased into the mild to normal range without the need for prophylactic immunosuppression. Treated patients were able to discontinue prophylaxis and bleeding was controlled in most of the cohort.
“This is a big advance and we are getting very close to the point where gene therapy is going to be standard of care for some forms of hemophilia,” said Brodsky. However, he added that “we will still need to see more patients and have longer follow-up.”
He added that, with time, the technology behind gene therapy will probably become less expensive and more accessible to more patients, which will help become a standard of care.
This is also the hope for the technology behind chimeric antigen receptor T-cell (CAR-T) therapy, he added. At present, this cellular therapy is manufactured individually for each patient and is very expensive, but work on “off-the-shelf” products is underway. This topic will be explored during the presidential symposium, entitled, “Universal Donor Solutions in Hematology.”
New data on one of the currently available CAR-T cell products will be presented at the meeting. The phase 2 ZUMA-5 trial showed that axicabtagene ciloleucel (Axi-Cel) may be a viable option for some patients with high-risk non-Hodgkin lymphoma who have not responded to standard treatments (abstract 700).
At a median follow-up of almost 18 months, 92% of participants achieved an objective response, and 78% achieved a complete response to the treatment. By 12 months, 72% were still in response, and at 17.5 months, 64% were still in response.
“We were very impressed with the magnitude of the responses, and also the durability,” said senior study author Caron Jacobson, MD, of the Dana-Farber Cancer Institute, Boston, in a press release. “I was also struck early on by how favorable the safety profile was compared to what we’ve been seeing in the fast-growing lymphomas, such as large B cell lymphoma.”
Race and bloods cancers
ASH president Stephanie Lee, MD, MPH, highlighted several abstracts on disparities that will be presented at the meeting. One of these, which is to be presented during the plenary session, is an analysis of patient survival in acute myeloid leukemia (AML) (abstract 6).
It found that “self-reported race was the best indicator of survival,” noted Lee.
Overall survival at 3 years was 41% in White patients versus 32% in Black patients, a difference that was highly significant, she noted.
Part of the study also evaluated patients who were all on the same chemotherapy protocol, “so there was no effect of different treatment since they were on therapy determined by the trial,” said Lee.
Black patients were less likely to have normal cytogenetics compared with White patients (38% vs 51%; P = .01) and had a lower frequency of prognostically favorable NPM1 mutations (25% vs 38%; P = .04), but higher frequencies of spliceosome gene mutations (24% vs 12%; P = .009). Therefore, the results showed race was an independent prognosticator of poor survival in AML, aside from established molecular markers.
A special scientific session on race will be held on Dec. 5, Lee noted. While other abstracts consider race from the patient side, this session will focus on the scientist’s side, she explained, and address questions such as: “What are the implications of diversity and racism? And how does that impact scientists who are from underrepresented minorities?”
COVID-19 and blood disorders
Lee also highlighted a study (abstract 215) that analyzed emerging data from the ASH Research Collaborative COVID-19 Registry for Hematology, which was developed to look at outcomes of COVID-19 infection in patients with underlying blood disorders.
An analysis of data from 250 patients at 74 sites around the world found that overall mortality was 28%. “This supports the emerging consensus that patients with hematologic malignancies experience significant morbidity and mortality from COVID-19 infection,” say the authors.
“We do need real-world data to see how SARS-CoV-2 is affecting our patients with hematologic diseases or those who don’t have a hematologic disease but who are then infected with the coronavirus and develop a hematologic problem like blood clots,” said Lee.
“More data will be coming in, but this is a good example of trying to harness real-world information to learn things until we have more controlled trials.”
‘Fireside chat’ with Fauci
COVID-19 will be on the agenda for a special session billed as a “fireside chat” with Anthony Fauci, MD, of the National Institute of Allergy and Infectious Diseases, National Institutes of Health.
“This will be kicking off our meeting on Saturday morning,” said Lee.
This article first appeared on Medscape.com.
Patient health suffers amid pandemic health care shortages
More than half (56%) of responding clinicians reported seeing a decline in patient health because of delayed or inaccessible care amid the pandemic, according to the results of the latest survey by the Larry A. Green Center and the Primary Care Collaborative. The survey was conducted in mid-October and the results were published online Nov. 17.
In addition, 37% of respondents said their patients with chronic conditions showed “noticeably worse health resulting from the pandemic.” And a resounding 85% said patient mental health had worsened.
“I think it’s worse than we thought,” said Rebecca Etz, PhD, codirector of the Larry Green Center. “It’s the outcome of not sufficiently sending resources to primary care either before or during the pandemic.” According to Dr. Etz, survey respondents noted substantial increases in patient weight gain as well as weight loss, anxiety and depression, sleep issues, domestic abuse, and poor oral and eye health, among others.
One clinician from Pennsylvania wrote: “Patients are becoming sicker during the pandemic. I’m seeing more uncontrolled [diabetes]and new [patients with diabetes]. They prefer telehealth yet [have] no access to glucose monitoring or a blood pressure cuff. I am concerned about patients’ isolation and mental health. People are delaying care.”
Now, with COVID numbers peaking across much of the country, many clinicians are trying to close the gap in care with telehealth – something they’re more prepared to do now than they were in March. Over two-thirds of practices are using telehealth for visits to keep up with patients who have stable chronic conditions, according to the survey.
Over 60% of physicians report using telehealth for mental health visits. But a much smaller number – only 16% of respondents – said their practice had added staff to help manage the rising number of behavioral and mental health cases. About one-third (35%) of practices say they’re not financially able to take on new staff.
“We’ve been looking for more ways for patients to do self-support. A big part of chronic disease is health behaviors,” Alex Krist, MD, MPH, a family doctor in Fairfax, Va., and chairperson of the U.S. Preventive Services Task Force, said in an interview. And unfortunately, on top of limited access to basic care, healthy habits that are essential to managing many chronic conditions have become more difficult and less consistent during the pandemic.
The survey – the 22nd iteration in a series of surveys the Green Center and the Primary Care Collaborative have conducted – received 580 respondents from 47 states and Guam. Over two-thirds of respondents were primary care physicians (MDs and DOs). Over half were owners, partners, or employees of a private practice, 66% of which were family medicine practices. And one fifth of respondents provided care in a rural area.
Funding and support for primary care has been wildly insufficient, Dr. Etz said in an interview. If that doesn’t change, patient health, clinic staffing, and public health strategies amid the pandemic will continue to suffer.
“When you think of the COVID vaccine, who do you think is going to be sending that out?” Dr. Etz asked. “If we don’t bolster primary care now how are they going to handle that.”
A version of this article originally appeared on Medscape.com.
More than half (56%) of responding clinicians reported seeing a decline in patient health because of delayed or inaccessible care amid the pandemic, according to the results of the latest survey by the Larry A. Green Center and the Primary Care Collaborative. The survey was conducted in mid-October and the results were published online Nov. 17.
In addition, 37% of respondents said their patients with chronic conditions showed “noticeably worse health resulting from the pandemic.” And a resounding 85% said patient mental health had worsened.
“I think it’s worse than we thought,” said Rebecca Etz, PhD, codirector of the Larry Green Center. “It’s the outcome of not sufficiently sending resources to primary care either before or during the pandemic.” According to Dr. Etz, survey respondents noted substantial increases in patient weight gain as well as weight loss, anxiety and depression, sleep issues, domestic abuse, and poor oral and eye health, among others.
One clinician from Pennsylvania wrote: “Patients are becoming sicker during the pandemic. I’m seeing more uncontrolled [diabetes]and new [patients with diabetes]. They prefer telehealth yet [have] no access to glucose monitoring or a blood pressure cuff. I am concerned about patients’ isolation and mental health. People are delaying care.”
Now, with COVID numbers peaking across much of the country, many clinicians are trying to close the gap in care with telehealth – something they’re more prepared to do now than they were in March. Over two-thirds of practices are using telehealth for visits to keep up with patients who have stable chronic conditions, according to the survey.
Over 60% of physicians report using telehealth for mental health visits. But a much smaller number – only 16% of respondents – said their practice had added staff to help manage the rising number of behavioral and mental health cases. About one-third (35%) of practices say they’re not financially able to take on new staff.
“We’ve been looking for more ways for patients to do self-support. A big part of chronic disease is health behaviors,” Alex Krist, MD, MPH, a family doctor in Fairfax, Va., and chairperson of the U.S. Preventive Services Task Force, said in an interview. And unfortunately, on top of limited access to basic care, healthy habits that are essential to managing many chronic conditions have become more difficult and less consistent during the pandemic.
The survey – the 22nd iteration in a series of surveys the Green Center and the Primary Care Collaborative have conducted – received 580 respondents from 47 states and Guam. Over two-thirds of respondents were primary care physicians (MDs and DOs). Over half were owners, partners, or employees of a private practice, 66% of which were family medicine practices. And one fifth of respondents provided care in a rural area.
Funding and support for primary care has been wildly insufficient, Dr. Etz said in an interview. If that doesn’t change, patient health, clinic staffing, and public health strategies amid the pandemic will continue to suffer.
“When you think of the COVID vaccine, who do you think is going to be sending that out?” Dr. Etz asked. “If we don’t bolster primary care now how are they going to handle that.”
A version of this article originally appeared on Medscape.com.
More than half (56%) of responding clinicians reported seeing a decline in patient health because of delayed or inaccessible care amid the pandemic, according to the results of the latest survey by the Larry A. Green Center and the Primary Care Collaborative. The survey was conducted in mid-October and the results were published online Nov. 17.
In addition, 37% of respondents said their patients with chronic conditions showed “noticeably worse health resulting from the pandemic.” And a resounding 85% said patient mental health had worsened.
“I think it’s worse than we thought,” said Rebecca Etz, PhD, codirector of the Larry Green Center. “It’s the outcome of not sufficiently sending resources to primary care either before or during the pandemic.” According to Dr. Etz, survey respondents noted substantial increases in patient weight gain as well as weight loss, anxiety and depression, sleep issues, domestic abuse, and poor oral and eye health, among others.
One clinician from Pennsylvania wrote: “Patients are becoming sicker during the pandemic. I’m seeing more uncontrolled [diabetes]and new [patients with diabetes]. They prefer telehealth yet [have] no access to glucose monitoring or a blood pressure cuff. I am concerned about patients’ isolation and mental health. People are delaying care.”
Now, with COVID numbers peaking across much of the country, many clinicians are trying to close the gap in care with telehealth – something they’re more prepared to do now than they were in March. Over two-thirds of practices are using telehealth for visits to keep up with patients who have stable chronic conditions, according to the survey.
Over 60% of physicians report using telehealth for mental health visits. But a much smaller number – only 16% of respondents – said their practice had added staff to help manage the rising number of behavioral and mental health cases. About one-third (35%) of practices say they’re not financially able to take on new staff.
“We’ve been looking for more ways for patients to do self-support. A big part of chronic disease is health behaviors,” Alex Krist, MD, MPH, a family doctor in Fairfax, Va., and chairperson of the U.S. Preventive Services Task Force, said in an interview. And unfortunately, on top of limited access to basic care, healthy habits that are essential to managing many chronic conditions have become more difficult and less consistent during the pandemic.
The survey – the 22nd iteration in a series of surveys the Green Center and the Primary Care Collaborative have conducted – received 580 respondents from 47 states and Guam. Over two-thirds of respondents were primary care physicians (MDs and DOs). Over half were owners, partners, or employees of a private practice, 66% of which were family medicine practices. And one fifth of respondents provided care in a rural area.
Funding and support for primary care has been wildly insufficient, Dr. Etz said in an interview. If that doesn’t change, patient health, clinic staffing, and public health strategies amid the pandemic will continue to suffer.
“When you think of the COVID vaccine, who do you think is going to be sending that out?” Dr. Etz asked. “If we don’t bolster primary care now how are they going to handle that.”
A version of this article originally appeared on Medscape.com.
Moderna filing for FDA emergency COVID-19 vaccine approval, reports 94.1% efficacy
The Moderna COVID-19 vaccine in development was 94.1% effective in the final analysis of its 30,000-participant phase 3 study. Bolstered by the new findings, the company plans to file for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) today, according to a company release.
A total of 11 people in the mRNA-1273 vaccinated group later tested positive for COVID-19, compared with 185 participants given two placebo injections, resulting in a point estimate of 94.1% efficacy. This finding aligns with the 94.5% efficacy in interim trial results announced on November 16, as reported by Medscape Medical News.
Furthermore, Moderna announced that the vaccine prevented serious cases of infection. All 30 severe infections occurred among those people randomly assigned to placebo.
The FDA plans to review the Moderna vaccine safety and efficacy data at the next Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for December 17. If and when approved, healthcare providers can use the new 91301 CPT code specific to mRNA-1273 vaccination.
“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and, importantly, the ability to prevent severe COVID-19 disease,” said Stéphane Bancel, MBA, MEng, chief executive officer of Moderna, in the news release. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations, and death.”
Vaccine efficacy remained consistent across different groups analyzed by age, race/ethnicity, and gender. The 196 COVID-19 cases in the trial included 33 adults older than 65 years and 42 people from diverse communities, including 29 Hispanic or Latinx, six Black or African Americans, four Asian Americans, and three multiracial participants, the company reported.
No serious vaccine-related safety issues
The mRNA-1273 vaccine was generally well tolerated and no serious safety concerns with the vaccine have been identified to date, the company reported.
Injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site were the most common solicited adverse events in a prior analysis. The company noted that these solicited adverse reactions increased in frequency and severity after the second vaccine dose. A continuous review of safety data is ongoing.
One COVID-19-related death in the study occurred in the placebo group.
Ready to start shipping
Moderna expects to have approximately 20 million doses of mRNA-1273 available in the United States by the end of this year. The company reports that it’s on track to manufacture 500 million to 1 billion doses globally in 2021.
The company also is seeking approval from nations and organizations worldwide, including a conditional approval from the European Medicines Agency (EMA). The study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.
Moderna will be the second company to file an EUA with the FDA for a COVID vaccine, after Pfizer requested one for its mRNA vaccine earlier this month.
This article first appeared on Medscape.com.
The Moderna COVID-19 vaccine in development was 94.1% effective in the final analysis of its 30,000-participant phase 3 study. Bolstered by the new findings, the company plans to file for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) today, according to a company release.
A total of 11 people in the mRNA-1273 vaccinated group later tested positive for COVID-19, compared with 185 participants given two placebo injections, resulting in a point estimate of 94.1% efficacy. This finding aligns with the 94.5% efficacy in interim trial results announced on November 16, as reported by Medscape Medical News.
Furthermore, Moderna announced that the vaccine prevented serious cases of infection. All 30 severe infections occurred among those people randomly assigned to placebo.
The FDA plans to review the Moderna vaccine safety and efficacy data at the next Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for December 17. If and when approved, healthcare providers can use the new 91301 CPT code specific to mRNA-1273 vaccination.
“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and, importantly, the ability to prevent severe COVID-19 disease,” said Stéphane Bancel, MBA, MEng, chief executive officer of Moderna, in the news release. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations, and death.”
Vaccine efficacy remained consistent across different groups analyzed by age, race/ethnicity, and gender. The 196 COVID-19 cases in the trial included 33 adults older than 65 years and 42 people from diverse communities, including 29 Hispanic or Latinx, six Black or African Americans, four Asian Americans, and three multiracial participants, the company reported.
No serious vaccine-related safety issues
The mRNA-1273 vaccine was generally well tolerated and no serious safety concerns with the vaccine have been identified to date, the company reported.
Injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site were the most common solicited adverse events in a prior analysis. The company noted that these solicited adverse reactions increased in frequency and severity after the second vaccine dose. A continuous review of safety data is ongoing.
One COVID-19-related death in the study occurred in the placebo group.
Ready to start shipping
Moderna expects to have approximately 20 million doses of mRNA-1273 available in the United States by the end of this year. The company reports that it’s on track to manufacture 500 million to 1 billion doses globally in 2021.
The company also is seeking approval from nations and organizations worldwide, including a conditional approval from the European Medicines Agency (EMA). The study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.
Moderna will be the second company to file an EUA with the FDA for a COVID vaccine, after Pfizer requested one for its mRNA vaccine earlier this month.
This article first appeared on Medscape.com.
The Moderna COVID-19 vaccine in development was 94.1% effective in the final analysis of its 30,000-participant phase 3 study. Bolstered by the new findings, the company plans to file for an emergency use authorization (EUA) from the Food and Drug Administration (FDA) today, according to a company release.
A total of 11 people in the mRNA-1273 vaccinated group later tested positive for COVID-19, compared with 185 participants given two placebo injections, resulting in a point estimate of 94.1% efficacy. This finding aligns with the 94.5% efficacy in interim trial results announced on November 16, as reported by Medscape Medical News.
Furthermore, Moderna announced that the vaccine prevented serious cases of infection. All 30 severe infections occurred among those people randomly assigned to placebo.
The FDA plans to review the Moderna vaccine safety and efficacy data at the next Vaccines and Related Biological Products Advisory Committee (VRBPAC) meeting scheduled for December 17. If and when approved, healthcare providers can use the new 91301 CPT code specific to mRNA-1273 vaccination.
“This positive primary analysis confirms the ability of our vaccine to prevent COVID-19 disease with 94.1% efficacy and, importantly, the ability to prevent severe COVID-19 disease,” said Stéphane Bancel, MBA, MEng, chief executive officer of Moderna, in the news release. “We believe that our vaccine will provide a new and powerful tool that may change the course of this pandemic and help prevent severe disease, hospitalizations, and death.”
Vaccine efficacy remained consistent across different groups analyzed by age, race/ethnicity, and gender. The 196 COVID-19 cases in the trial included 33 adults older than 65 years and 42 people from diverse communities, including 29 Hispanic or Latinx, six Black or African Americans, four Asian Americans, and three multiracial participants, the company reported.
No serious vaccine-related safety issues
The mRNA-1273 vaccine was generally well tolerated and no serious safety concerns with the vaccine have been identified to date, the company reported.
Injection site pain, fatigue, myalgia, arthralgia, headache, and erythema/redness at the injection site were the most common solicited adverse events in a prior analysis. The company noted that these solicited adverse reactions increased in frequency and severity after the second vaccine dose. A continuous review of safety data is ongoing.
One COVID-19-related death in the study occurred in the placebo group.
Ready to start shipping
Moderna expects to have approximately 20 million doses of mRNA-1273 available in the United States by the end of this year. The company reports that it’s on track to manufacture 500 million to 1 billion doses globally in 2021.
The company also is seeking approval from nations and organizations worldwide, including a conditional approval from the European Medicines Agency (EMA). The study is being conducted in collaboration with the National Institute of Allergy and Infectious Diseases (NIAID) and the Biomedical Advanced Research and Development Authority (BARDA), part of the Office of the Assistant Secretary for Preparedness and Response at the US Department of Health and Human Services.
Moderna will be the second company to file an EUA with the FDA for a COVID vaccine, after Pfizer requested one for its mRNA vaccine earlier this month.
This article first appeared on Medscape.com.
Blood glucose on admission predicts COVID-19 severity in all
Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.
The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.
Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history.
Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.
“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.
The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.
However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
Pay attention to even mild hyperglycemia from admission
The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.
Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.
“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.
“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.
The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”
However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
All-cause death, progress to critical care higher with hyperglycemia
The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.
Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.
After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)
Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).
Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001).
The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.
The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.
Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history.
Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.
“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.
The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.
However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
Pay attention to even mild hyperglycemia from admission
The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.
Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.
“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.
“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.
The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”
However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
All-cause death, progress to critical care higher with hyperglycemia
The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.
Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.
After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)
Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).
Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001).
The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hyperglycemia at hospital admission – regardless of diabetes status – is a key predictor of COVID-19-related death and severity among noncritical patients, new research from Spain finds.
The observational study, the largest to date to investigate this association, was published online Nov. 23 in Annals of Medicine by Francisco Javier Carrasco-Sánchez, MD, PhD, and colleagues.
Among more than 11,000 patients with confirmed COVID-19 from March to May 2020 in a nationwide Spanish registry involving 109 hospitals, admission hyperglycemia independently predicted progression from noncritical to critical condition and death, regardless of prior diabetes history.
Those with abnormally high glucose levels were more than twice as likely to die from the virus than those with normal readings (41.4% vs 15.7%). They also had an increased need for a ventilator and intensive care unit (ICU) admission.
“These results provided a simple and practical way to stratify risk of death in hospitalized patients with COVID-19. Hence, admission hyperglycemia should not be overlooked, but rather detected and appropriately treated to improve the outcomes of COVID-19 patients with and without diabetes,” Dr. Carrasco-Sánchez and colleagues wrote.
The findings confirm those of previous retrospective observational studies, but the current study “has, by far, the biggest number of patients involved in this kind of study [to date]. All conclusions are consistent to other studies,” Dr. Carrasco-Sánchez, of University Hospital Juan Ramón Jiménez, Huelva, Spain, said in an interview.
However, a surprising finding, he said, “was how hyperglycemia works in the nondiabetic population and [that] glucose levels over 140 [mg/dL] ... increase the risk of death.”
Pay attention to even mild hyperglycemia from admission
The study also differs from some of the prior observational ones in that it examines outcome by admission glycemia rather than during the hospital stay, therefore eliminating the effect of any inpatient treatment, such as dexamethasone, he noted.
Although blood glucose measurement at admission is routine for all patients in Spain, as it is in the United States and elsewhere, a mildly elevated level in a person without a diagnosis of diabetes may not be recognized as important.
“In patients with diabetes we start the protocol to control and treat hyperglycemia during hospitalization. However, in nondiabetic patients blood glucose levels under 180 [mg/dL], and even greater, are usually overlooked. This means there is not a correct follow-up of the patients during hospitalization.
“After this study we learned that we need to pay attention to this population ... who develop hyperglycemia from the beginning,” he said.
The study was limited in that patients who had previously undiagnosed diabetes couldn’t always be distinguished from those with acute “stress hyperglycemia.”
However, both need to be managed during hospitalization, he said. “Unfortunately, there is high variability in inpatient glucose management. The working group of diabetes of the Spanish Society of Internal Medicine is working on specific protocols,” said Dr. Carrasco-Sánchez.
All-cause death, progress to critical care higher with hyperglycemia
The retrospective, multicenter study was based on data from 11,312 adult patients with confirmed COVID-19 in 109 hospitals participating in Spain’s SEMI-COVID-19 registry as of May 29, 2020. They had a mean age of 67 years, 57% were male, and 19% had a diagnosis of diabetes. A total of 20% (n = 2,289) died during hospitalization.
Overall all-cause mortality was 41.1% among those with admission blood glucose levels above 180 mg/dL, 33.0% for those with glucose levels 140-180 mg/dL, and 15.7% for levels below 140 mg/dL. All differences were significant (P < .0001), but there were no differences in mortality rates within each blood glucose category between patients with or without a previous diagnosis of diabetes.
After adjustment for confounding factors, elevated admission blood glucose level remained a significant predictor of death. Compared to < 140 mg/dL, the hazard ratios for 140-180 mg/dL and > 180 mg/dL were 1.48 and 1.50, respectively (both P < .001). (Adjustments included age, gender, hypertension, diabetes, chronic obstructive pulmonary disease, lymphopenia, anemia (hemoglobin < 10 g/dL), serum creatinine, C-reactive protein > 60 mg/L, lactate dehydrogenase > 400 U/L and D-dimer >1000 ng/mL.)
Length of stay was 12, 11.5, and 11.1 days for those with admission blood glucose levels > 180, 140-180, and < 140 mg/dL, respectively (P = .011).
Use of mechanical ventilation and admission to intensive care also rose with higher admission blood glucose levels. For the composite of death, mechanical ventilation, and/or ICU admission, odds ratios for 140-180 mg/dL and > 180 mg/dL compared with < 140 mg/dL were 1.70 and 2.02, respectively (both P < .001).
The study was supported by the Spanish Federation of Internal Medicine. The authors have reported no relevant financial relationships.
A version of this article originally appeared on Medscape.com.
Hemochromatosis variants may confer 10-fold higher risk of liver cancer
Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.
In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.
Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.
For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.
Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
Results: Increased risks for men, not women
The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.
Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.
At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).
The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P = .046).
In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.
Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.
The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
Implications: Earlier diagnosis and treatment
The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.
“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.
“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.
“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.
“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.
“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.
This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.
SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.
Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.
In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.
Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.
For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.
Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
Results: Increased risks for men, not women
The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.
Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.
At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).
The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P = .046).
In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.
Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.
The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
Implications: Earlier diagnosis and treatment
The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.
“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.
“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.
“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.
“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.
“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.
This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.
SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.
Hereditary hemochromatosis is primarily caused by HFE gene variants. Past research suggested that 81% of patients with hereditary hemochromatosis carry the p.C282Y variant and 5% carry the p.C282Y/p.H63D compound heterozygote genotype.
In a new study, the presence of HFE p.C282Y and p.H63D genotypes was associated with a 10-fold greater risk of developing a hepatic malignancy among men of European ancestry aged 40-70 years. In addition, men with HFE variants were 1.2 times more likely to die of any cause, compared with men who had neither pathogenic variant.
Janice L. Atkins, PhD, of the University of Exeter (England), and colleagues reported these findings in JAMA.
For this study, Dr. Atkins and colleagues used follow-up data from a large genotyped community sample to estimate the incidence of primary hepatic carcinomas and deaths by HFE variant status in participants of European descent.
Data for the two linked coprimary endpoints, incident primary liver carcinoma and all-cause mortality, were derived from hospital and death certificate records. Where available, primary care data was also included.
Results: Increased risks for men, not women
The researchers analyzed data from 451,186 men and women, aged 40-70 years, from the UK Biobank. There were 2,890 (0.9%) patients who were p.C282Y homozygous, 1,294 of whom were men.
Among the 1,294 men with HFE p.C282Y homozygosity, 21 were diagnosed with a primary hepatic malignancy. Ten of these patients were not diagnosed with hemochromatosis at baseline.
At a median follow-up of 8.9 years, the risk of primary hepatic malignancy was significantly higher in men with HFE p.C282Y homozygosity, compared with men without HFE pathogenic variants (hazard ratio, 10.5; 95% confidence interval, 6.6-16.7; P < .001).
The risk of all-cause death was significantly higher in men with HFE p.C282Y homozygosity as well (HR, 1.2; 95% CI, 1.0-1.5; P = .046).
In contrast, female HFE p.C282Y homozygotes had no significant increases in the risk of incident primary hepatic malignancy or all-cause mortality.
Life table projections estimated that 7.2% of men with HFE p.C282Y homozygosity will develop a primary hepatic malignancy by age 75, compared with 0.6% of men without p.C282Y or p.H63D variants.
The researchers acknowledged that a key limitation of this study was the ancestral homogeneity of the cohort. Thus, the findings may not be generalizable to all patient populations.
Implications: Earlier diagnosis and treatment
The results of this study underline the importance of early diagnosis and genetic testing, according to the researchers.
“Tragically, men with the hemochromatosis faulty genes have been dying of liver cancer for many years, but this was thought to be rare,” study author David Melzer, MBBCh, PhD, of University of Exeter, said in a press release.
“The large scale of the UK Biobank study allowed us to measure cancer risk accurately. We were shocked to find that more than 7% of men with two faulty genes are likely to develop liver cancer by age 75, particularly considering that the U.K. has the second-highest rate of these faulty genes in the world. Fortunately, most of these cancers could be prevented with early treatment,” Dr. Melzer added.
“Physicians and scientists have long acknowledged that iron overload is an important cofactor fueling the development of many serious diseases, including cancer,” said study author Jeremy Shearman, MBChB, DPhil, of Nuffield Health and South Warwickshire NHS Foundation Trust in the United Kingdom.
“This research is a vital step towards quantifying that risk and should raise awareness of the importance of iron in the minds of both clinicians and patients. Measurement of iron stores and recognition of the genetic risk of iron overload needs to become a routine part of health assessment and monitoring in the U.K.,” Dr. Shearman added.
“The UK Biobank project is a glimpse into the future of medicine where all known genes are tested and then treatable conditions are offered treatment before serious complications develop,” said study author Paul Adams, MD, of the University of Western Ontario in London.
This research was funded by the UK Medical Research Council. Dr. Melzer disclosed financial affiliations with the UK Medical Research Council during the conduct of the study.
SOURCE: Atkins JL et al. JAMA. 2020 Nov 24. doi: 10.1001/jama.2020.21566.
FROM JAMA
Approval of COVID-19 vaccines will change nature of clinical trials
While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.
In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”
In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.
“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”
Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”
Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.
In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.
In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.
Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.
The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.
“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted.
More data with more study designs
Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.
“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.
Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.
With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.
“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”
For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.
It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.
“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”
Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
‘A lot of redundancy’
Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.
“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.
“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”
Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.
The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.
“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”
A version of this article originally appeared on Medscape.com.
While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.
In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”
In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.
“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”
Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”
Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.
In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.
In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.
Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.
The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.
“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted.
More data with more study designs
Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.
“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.
Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.
With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.
“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”
For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.
It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.
“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”
Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
‘A lot of redundancy’
Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.
“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.
“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”
Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.
The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.
“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”
A version of this article originally appeared on Medscape.com.
While stressing the urgent need to vaccinate the whole U.S. population, infectious disease experts and medical ethicists are raising questions about the clinical trials needed to answer important questions about the new COVID-19 vaccines.
In a statement released on Nov. 20, Barbara Alexander, MD, president of the Infectious Diseases Society of America (IDSA) and a professor at Duke University, Durham, N.C., commented on Pfizer and BioNTech’s application to the Food and Drug Administration for an emergency use authorization (EUA) for its COVID-19 vaccine. Besides emphasizing the need for a transparent review of the companies’ trial data prior to the FDA’s granting an EUA, she said, “If emergency use authorization is granted, clinical trials and data collection must continue.”
In an interview, Dr. Alexander said she is convinced that both Pfizer and Moderna, which is also expected to seek an EUA soon, will continue their clinical trials to monitor the long-term safety and efficacy of their vaccines.
“The EUA guidance for COVID vaccine authorization is very clear that clinical trials will move forward,” she said. “Any EUA request would have to include a strategy to ensure that the long-term safety and efficacy of a vaccine could be monitored. I see no evidence that either Pfizer or Moderna is not prepared to follow those regulations.”
Eventually, she added, the drug makers will have to seek full FDA approval to replace an EUA, which as its name signifies, is designed for public health emergencies. “The EUA is a tool to help us get the vaccine into circulation and have it start working as quickly as possible in the current health crisis,” she said. “But once the crisis is over, if the sponsors want to continue to market their vaccines, they have to go forward and get full approval.”
Medical ethicists, however, point out there may be ethical and practical dilemmas involved in continuing or initiating clinical trials once a vaccine has been approved for use even on an emergency basis.
In a commentary in Annals of Internal Medicine, Rafael Dal-Re, MD, PhD, Arthur L. Caplan, PhD, and two other ethicists stipulated that the pandemic requires early licensing and deployment of COVID-19 vaccines. Nevertheless, they noted, additional months of data are required to establish the long-term efficacy and safety of the vaccines. “Moreover, early deployment could interfere with the acquisition of long-term data,” both on these vaccines and on others coming through the pipeline, they wrote.
In countries where an approved vaccine is deployed, the ethicists noted, investigators must inform participants in an ongoing trial about the approved vaccine’s status and ask if they want to continue in the study. If enough participants decline, the trial might have to be terminated early. At that point, researchers may not have sufficient long-term data to identify late-term safety issues, determine how long efficacy lasts, determine whether waning immunity is associated with reduced levels of antibodies, or identify the level of neutralizing antibodies that correlates with immunity.
Moreover, they observed, long-term trials are especially important for vaccines that use mRNA technology, because less is known about them than about traditional kinds of vaccines.
The authors also pointed out that early licensing of any vaccine might make it harder to evaluate vaccines that haven’t yet been approved. “Once a vaccine is licensed, new placebo-controlled RCTs [randomized controlled trials] of other vaccines will not be acceptable ethically, and noninferiority RCTs will be the most likely alternative.
“The goal of noninferiority trials will be to demonstrate that the immune response (that is, neutralizing antibody titers or levels) of the candidate vaccine is not inferior to that of the approved vaccine within a prespecified margin, which the FDA has established as less than 10% for COVID-19 vaccines,” the authors noted.
More data with more study designs
Dial Hewlett Jr., MD, medical director for disease control services, Westchester County Department of Health, White Plains, N.Y., said in an interview that the ethicists raise important issues that have been discussed in other forums, including a recent webinar of the National Academy of Medicine.
“As the authors point out, once you have a vaccine that has been shown to be effective and safe, it’s no longer ethical to enroll people in placebo trials,” he said.
Therefore, he said, Pfizer and Moderna will undoubtedly offer their vaccines to the people in their studies’ placebo groups after the vaccines receive an EUA. Then they will follow everyone who has been vaccinated for 2 years to determine long-term safety. Efficacy will also continue to be measured as an adjunct of safety, he said.
With regard to the difficulty of reconsenting individuals to enter a new clinical trial after a vaccine has been approved, he said, “I’d agree that trying to get all the same participants to come into another study would be a challenge. You can, however, design studies that will allow you to obtain the same information. You will have a large number of people out there who haven’t been vaccinated, and you can do single-arm longitudinal studies and measure a number of things in the individuals who are enrolled in those studies,” he said.
“You can look at the immunologic markers, both antibody and T-cell. You can follow these individuals longitudinally to see if they do develop disease over a period of time. If they do, you can determine what their levels of response were,” he added. “So there are opportunities to design studies that would give you some of the same information, although it would not be in the same population that was in the randomized trials.”
For newer vaccines that have yet to be tested, he said, developers can compare “historical controls” from the trials of approved vaccines, i.e., data from the unvaccinated participants in those studies, with the data from inoculating people with the novel agents. The historical data can be sex- and age-matched, among other things, to individuals in the new trials. Moreover, because the study protocols have been harmonized for all trials under Operation Warp Speed, it doesn’t matter what kind of vaccine they’re testing, he said.
It may be necessary to do additional studies to find out how long immunity lasts after people have been vaccinated, Dr. Hewlett pointed out.
“You may have a different trial design. You don’t need a control arm to determine how long immunity lasts. You’re just comparing the patients who were vaccinated to nothing,” he said. “So you could have a single-arm trial on a group of people who consent to be immunized and followed. You can see what their antibody levels are and other surrogate markers, and you can see when they might develop disease, if they do. You’d need a large sample, but you can do that.”
Dr. Hewlett noted that additional studies will be required to determine whether the new vaccines stop transmission of the coronavirus or just prevent symptoms of COVID-19. Until it’s established that a vaccine halts transmission or the country achieves herd immunity, he said, “we’ll still have to wear masks and take other precautions, because a significant portion of people will still be at risk.”
‘A lot of redundancy’
Dr. Alexander emphasized that any safety or efficacy issues with the first COVID-19 vaccines must be identified before the vaccine is offered to a large portion of the U.S. population.
“While the data from the Pfizer and Moderna trials are said to be favorable, we at IDSA want to make sure that whatever vaccine comes to market is safe,” she said. “Having an unsafe vaccine on the market would be worse than no vaccine, because you’re compromising the public confidence. We have to make sure the public trusts the process and that sufficient data have been evaluated to ensure the vaccine is safe and efficacious.
“I believe the FDA is being very careful and thoughtful in [its] response,” Dr. Alexander said. “They realize how important it is to get a vaccine and save lives. While they’re doing things differently and moving much faster than before, they’re still trying to be thoughtful and reasonable. They don’t seem to be putting people at risk or circumventing the regulatory standards.”
Moreover, she pointed out, the FDA’s Vaccines and Related Biological Products Advisory Committee, which is expected to meet on Dec. 10, will review the trial data before the agency grants an EUA to Pfizer or Moderna. Then the FDA will post the data publicly.
The next step is for the Advisory Committee on Immunization Practices of the Centers for Disease Control and Prevention to look at the data and decide who in the United States should receive the vaccine first, she pointed out. And both Pfizer and Moderna have shown their data to advisory panels of outside experts.
“There’s a lot of redundancy, and a lot of people are looking at the data,” Dr. Alexander said. “So I don’t think we’re cutting corners to get it out there more quickly.”
A version of this article originally appeared on Medscape.com.
Immune checkpoint inhibitors don’t increase COVID-19 incidence or mortality, studies suggest
Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.
However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.
In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).
In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).
Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
COVID-19 incidence with ICIs
Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.
The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).
In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).
Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.
“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”
COVID-19 mortality with ICIs
For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.
Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.
In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.
Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).
At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.
The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.
“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.
“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
ICI therapy can continue, with precautions
“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.
“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.
However, the findings of the study by Tyan and colleagues are more “thought-provoking,” Dr. Doroshow said. She noted that a large study published in Nature Medicine showed previous ICI therapy in cancer patients with COVID-19 increased the risk for hospitalization or severe COVID-19 requiring high-flow oxygen or mechanical ventilation. The new study was much smaller and did not perform statistical comparisons for outcomes such as oxygen requirements.
“I would feel comfortable telling patients that the data suggests that ICI treatment does not increase their risk of COVID-19. However, if they were to be diagnosed with COVID-19, it is unclear whether their previous ICI treatment increases their risk for poor outcomes,” Dr. Doroshow said.
“I would feel comfortable continuing to treat patients with ICIs at this time, but because we know that patients with cancer are generally more likely to develop COVID-19 and have poor outcomes, it is critical that our patients be educated about social distancing and mask wearing to the extent that their living and working situations permit,” she added.
Mr. Pahalyants disclosed no relevant conflicts of interest, and his study did not receive any specific funding. Mr. Tyan disclosed that he is cofounder and chief science officer of Kinnos, and his study did not receive any specific funding. Dr. Doroshow disclosed no relevant conflicts of interest.
SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.
Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.
However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.
In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).
In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).
Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
COVID-19 incidence with ICIs
Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.
The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).
In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).
Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.
“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”
COVID-19 mortality with ICIs
For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.
Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.
In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.
Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).
At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.
The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.
“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.
“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
ICI therapy can continue, with precautions
“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.
“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.
However, the findings of the study by Tyan and colleagues are more “thought-provoking,” Dr. Doroshow said. She noted that a large study published in Nature Medicine showed previous ICI therapy in cancer patients with COVID-19 increased the risk for hospitalization or severe COVID-19 requiring high-flow oxygen or mechanical ventilation. The new study was much smaller and did not perform statistical comparisons for outcomes such as oxygen requirements.
“I would feel comfortable telling patients that the data suggests that ICI treatment does not increase their risk of COVID-19. However, if they were to be diagnosed with COVID-19, it is unclear whether their previous ICI treatment increases their risk for poor outcomes,” Dr. Doroshow said.
“I would feel comfortable continuing to treat patients with ICIs at this time, but because we know that patients with cancer are generally more likely to develop COVID-19 and have poor outcomes, it is critical that our patients be educated about social distancing and mask wearing to the extent that their living and working situations permit,” she added.
Mr. Pahalyants disclosed no relevant conflicts of interest, and his study did not receive any specific funding. Mr. Tyan disclosed that he is cofounder and chief science officer of Kinnos, and his study did not receive any specific funding. Dr. Doroshow disclosed no relevant conflicts of interest.
SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.
Cytokine storm plays a major role in the pathogenesis of COVID-19, according to research published in The Lancet Respiratory Medicine. This has generated concern about using ICIs during the pandemic, given their immunostimulatory activity and the risk of immune-related adverse effects.
However, two retrospective studies suggest ICIs do not increase the risk of developing COVID-19 or dying from the disease.
In a study of 1,545 cancer patients prescribed ICIs and 20,418 matched controls, the incidence of COVID-19 was 1.4% with ICI therapy and 1.0% without it (odds ratio, 1.38; P = .15).
In a case-control study of 50 patients with cancer and COVID-19, 28% of patients who had received ICIs died from COVID-19, compared with 36% of patients who had not received ICIs (OR, 0.36; P = .23).
Vartan Pahalyants and Kevin Tyan, both students in Harvard University’s joint MD/MBA program in Boston, presented these studies at the meeting.
COVID-19 incidence with ICIs
Mr. Pahalyants and colleagues analyzed data from cancer patients treated in the Mass General Brigham health care system. The researchers compared 1,545 patients with at least one ICI prescription between July 1, 2019, and Feb. 29, 2020, with 20,418 matched cancer patients not prescribed ICIs. The team assessed COVID-19 incidence based on positive test results through June 19, 2020, from public health data.
The incidence of COVID-19 was low in both groups – 1.4% in the ICI group and 1.0% in the matched control group (P = .16). Among COVID-19–positive patients, the all-cause death rate was 40.9% in the ICI group and 28.6% in the control group (P = .23).
In multivariate analysis, patients prescribed ICIs did not have a significantly elevated risk for COVID-19 relative to peers not prescribed ICIs (OR, 1.38; P = .15). However, risk was significantly increased for female patients (OR, 1.74; P < .001), those living in a town or county with higher COVID-19 positivity rate (OR, 1.59; P < .001), and those with severe comorbidity (vs. mild or moderate; OR, 9.77; P = .02).
Among COVID-19–positive patients, those prescribed ICIs did not have a significantly elevated risk for all-cause mortality (OR, 1.60; P = .71), but male sex and lower income were associated with an increased risk of death.
“We did not identify an increased risk of [COVID-19] diagnosis among patients prescribed ICIs compared to the controls,” Mr. Pahalyants said. “This information may assist patients and their providers in decision-making around continuation of therapy during this protracted pandemic. However, more research needs to be conducted to determine potential behavioral and testing factors that may have affected COVID-19 diagnosis susceptibility among patients included in the study.”
COVID-19 mortality with ICIs
For their study, Mr. Tyan and colleagues identified 25 cancer patients who had received ICIs in the year before a COVID-19 diagnosis between March 20, 2020, and June 3, 2020, at the Dana-Farber Cancer Institute and Mass General Brigham network. The researchers then matched each patient with a cancer patient having a COVID-19 diagnosis who had not received ICIs during the preceding year.
Overall, 28% of patients who had received ICIs before their COVID-19 diagnosis died from COVID-19, compared with 36% of those who had not received ICIs.
In multivariate analysis, ICI therapy did not predict COVID-19 mortality (OR, 0.36; P = .23). However, the risk of death from COVID-19 increased with age (OR, 1.14; P = .01) and for patients with chronic obstructive pulmonary disease (OR, 12.26; P = .01), and risk was lower for statin users (OR, 0.08; P = .02). Findings were similar in an analysis restricted to hospitalized patients in the ICI group and their matched controls.
Two ICI-treated patients with COVID-19 had persistent immune-related adverse events (hypophysitis in both cases), and one ICI-treated patient developed a new immune-related adverse event (hypothyroidism).
At COVID-19 presentation, relative to counterparts who had not received ICIs, patients who had received ICIs had higher platelet counts (P = .017) and higher D-dimer levels (P = .037). In the context of similar levels of other biomarkers, this finding is “of unclear significance, as all deaths in the cohort were due to respiratory failure as opposed to hypercoagulability,” Mr. Tyan said.
The patients treated with ICIs were more likely to die from COVID-19 if they had elevated troponin levels (P = .01), whereas no such association was seen for those not treated with ICIs.
“We found that ICI therapy is not associated with greater risk for COVID-19 mortality. Our period of follow-up was relatively short, but we did not observe a high incidence of new or persistent immune-related adverse events among our patients taking ICIs,” Mr. Tyan said.
“While larger prospective trials are needed to evaluate long-term safety in the context of COVID-19 infection, our findings support the continuation of ICI therapy during the pandemic as it does not appear to worsen outcomes for cancer patients,” he concluded.
ICI therapy can continue, with precautions
“The question of susceptibility to COVID-19 has been unclear as ICIs do not necessarily cause immunosuppression but certainly result in modulation of a patient’s immune system,” said Deborah Doroshow, MD, PhD, assistant professor at the Tisch Cancer Institute Icahn School of Medicine at Mount Sinai, New York. She was not involved in these studies.
“The findings of the study by Pahalyants and colleagues, which used a very large sample size, appear to convincingly demonstrate that ICI receipt is not associated with an increased susceptibility to COVID-19,” Dr. Doroshow said in an interview.
However, the findings of the study by Tyan and colleagues are more “thought-provoking,” Dr. Doroshow said. She noted that a large study published in Nature Medicine showed previous ICI therapy in cancer patients with COVID-19 increased the risk for hospitalization or severe COVID-19 requiring high-flow oxygen or mechanical ventilation. The new study was much smaller and did not perform statistical comparisons for outcomes such as oxygen requirements.
“I would feel comfortable telling patients that the data suggests that ICI treatment does not increase their risk of COVID-19. However, if they were to be diagnosed with COVID-19, it is unclear whether their previous ICI treatment increases their risk for poor outcomes,” Dr. Doroshow said.
“I would feel comfortable continuing to treat patients with ICIs at this time, but because we know that patients with cancer are generally more likely to develop COVID-19 and have poor outcomes, it is critical that our patients be educated about social distancing and mask wearing to the extent that their living and working situations permit,” she added.
Mr. Pahalyants disclosed no relevant conflicts of interest, and his study did not receive any specific funding. Mr. Tyan disclosed that he is cofounder and chief science officer of Kinnos, and his study did not receive any specific funding. Dr. Doroshow disclosed no relevant conflicts of interest.
SOURCE: Pahalyants V et al. SITC 2020, Abstract 826. Tyan K et al. SITC 2020, Abstract 481.
FROM SITC 2020