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ZUMA-2, TRANSCEND data pique interest in earlier CAR T for R/R MCL
The “remarkable” efficacy of chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory mantle cell lymphoma as observed in recent trials supports its evaluation earlier in the course of treatment, according to Roch Houot, MD, PhD.
Patients with relapsed or refractory mantle cell lymphoma (MCL) who progress after treatment with a Bruton’s tyrosine kinase inhibitor (BTKi) have poor clinical outcomes, Dr. Houot, professor of hematology at Rennes (France) University Hospital, explained at the 3rd European CAR T-cell meeting.
Objective response rates in patients who relapse after BTKi therapy range from 25% to 42%, and median overall survival (OS) is less than 10 months with standard therapies, he said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.
The recent ZUMA-2 and TRANSCEND NHL 001 trials evaluating the CD19 CAR T-cell products brexucabtagene autoleucel (brexu-cel; Tecartus) and lisocabtagene maraleucel (liso-cel; Breyanzi), respectively, in patients with relapsed or refractory MCL after BTKi therapy, showed dramatically improved outcomes, compared with outcomes seen previously with standard salvage therapies.
The ORR in 68 patients treated with brexu-cel in ZUMA-2 was 92%, including complete response (CR) in 40 patients (67%) and partial response (PR) in 15 patients (25%) with the rare, aggressive subtype of B-cell lymphoma.
“Interestingly, among patients who achieved a CR, 70% remained in remission after a median follow-up of 17.5 months,” he said.
Median duration of response, progression-free survival, and overall survival were not reached at that time, and ongoing responses were consistent across prognostic subgroups, he added.
The ZUMA-2 findings led to accelerated approval of brexu-cel by the Food and Drug Administration in July 2020, as well as priority medicine designation by the European Medicines Agency in December 2020, for the treatment of MCL after two or more prior lines of systemic therapy including a BTKi.
The TRANSCEND study also included patients with MCL who were relapsed or refractory after two or more lines of therapy.
The ORR was 84% in 32 patients who completed treatment – including CRs in 66% and PRs in 19%. An additional 3% had stable disease and 9% of patients progressed, Dr. Houot said.
“The follow-up of the TRANSCEND study is still very short – the median is 5.9 months – so we don’t have survival data yet for these patients,” he noted.
Still, the efficacy in these studies is excellent, particularly considering the challenges of treating MCL patients who relapse or are refractory after BTKi treatment, he said, noting that most patients in both studies had poor prognostic factors.
Toxicities in both studies were similar to those seen in studies of patients with aggressive B-cell lymphomas who were treated with these drugs, he added.
“Longer follow-up is needed to better evaluate long-term efficacy,” he said, concluding that the results nonetheless “support evaluation of CAR T-cell therapy earlier in the therapeutic strategy of mantle cell lymphoma.”
Dr. Houot reported having no disclosures.
The “remarkable” efficacy of chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory mantle cell lymphoma as observed in recent trials supports its evaluation earlier in the course of treatment, according to Roch Houot, MD, PhD.
Patients with relapsed or refractory mantle cell lymphoma (MCL) who progress after treatment with a Bruton’s tyrosine kinase inhibitor (BTKi) have poor clinical outcomes, Dr. Houot, professor of hematology at Rennes (France) University Hospital, explained at the 3rd European CAR T-cell meeting.
Objective response rates in patients who relapse after BTKi therapy range from 25% to 42%, and median overall survival (OS) is less than 10 months with standard therapies, he said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.
The recent ZUMA-2 and TRANSCEND NHL 001 trials evaluating the CD19 CAR T-cell products brexucabtagene autoleucel (brexu-cel; Tecartus) and lisocabtagene maraleucel (liso-cel; Breyanzi), respectively, in patients with relapsed or refractory MCL after BTKi therapy, showed dramatically improved outcomes, compared with outcomes seen previously with standard salvage therapies.
The ORR in 68 patients treated with brexu-cel in ZUMA-2 was 92%, including complete response (CR) in 40 patients (67%) and partial response (PR) in 15 patients (25%) with the rare, aggressive subtype of B-cell lymphoma.
“Interestingly, among patients who achieved a CR, 70% remained in remission after a median follow-up of 17.5 months,” he said.
Median duration of response, progression-free survival, and overall survival were not reached at that time, and ongoing responses were consistent across prognostic subgroups, he added.
The ZUMA-2 findings led to accelerated approval of brexu-cel by the Food and Drug Administration in July 2020, as well as priority medicine designation by the European Medicines Agency in December 2020, for the treatment of MCL after two or more prior lines of systemic therapy including a BTKi.
The TRANSCEND study also included patients with MCL who were relapsed or refractory after two or more lines of therapy.
The ORR was 84% in 32 patients who completed treatment – including CRs in 66% and PRs in 19%. An additional 3% had stable disease and 9% of patients progressed, Dr. Houot said.
“The follow-up of the TRANSCEND study is still very short – the median is 5.9 months – so we don’t have survival data yet for these patients,” he noted.
Still, the efficacy in these studies is excellent, particularly considering the challenges of treating MCL patients who relapse or are refractory after BTKi treatment, he said, noting that most patients in both studies had poor prognostic factors.
Toxicities in both studies were similar to those seen in studies of patients with aggressive B-cell lymphomas who were treated with these drugs, he added.
“Longer follow-up is needed to better evaluate long-term efficacy,” he said, concluding that the results nonetheless “support evaluation of CAR T-cell therapy earlier in the therapeutic strategy of mantle cell lymphoma.”
Dr. Houot reported having no disclosures.
The “remarkable” efficacy of chimeric antigen receptor (CAR) T-cell therapy for relapsed or refractory mantle cell lymphoma as observed in recent trials supports its evaluation earlier in the course of treatment, according to Roch Houot, MD, PhD.
Patients with relapsed or refractory mantle cell lymphoma (MCL) who progress after treatment with a Bruton’s tyrosine kinase inhibitor (BTKi) have poor clinical outcomes, Dr. Houot, professor of hematology at Rennes (France) University Hospital, explained at the 3rd European CAR T-cell meeting.
Objective response rates in patients who relapse after BTKi therapy range from 25% to 42%, and median overall survival (OS) is less than 10 months with standard therapies, he said at the meeting, which is jointly sponsored by the European Society for Blood and Marrow Transplantation and the European Hematology Association.
The recent ZUMA-2 and TRANSCEND NHL 001 trials evaluating the CD19 CAR T-cell products brexucabtagene autoleucel (brexu-cel; Tecartus) and lisocabtagene maraleucel (liso-cel; Breyanzi), respectively, in patients with relapsed or refractory MCL after BTKi therapy, showed dramatically improved outcomes, compared with outcomes seen previously with standard salvage therapies.
The ORR in 68 patients treated with brexu-cel in ZUMA-2 was 92%, including complete response (CR) in 40 patients (67%) and partial response (PR) in 15 patients (25%) with the rare, aggressive subtype of B-cell lymphoma.
“Interestingly, among patients who achieved a CR, 70% remained in remission after a median follow-up of 17.5 months,” he said.
Median duration of response, progression-free survival, and overall survival were not reached at that time, and ongoing responses were consistent across prognostic subgroups, he added.
The ZUMA-2 findings led to accelerated approval of brexu-cel by the Food and Drug Administration in July 2020, as well as priority medicine designation by the European Medicines Agency in December 2020, for the treatment of MCL after two or more prior lines of systemic therapy including a BTKi.
The TRANSCEND study also included patients with MCL who were relapsed or refractory after two or more lines of therapy.
The ORR was 84% in 32 patients who completed treatment – including CRs in 66% and PRs in 19%. An additional 3% had stable disease and 9% of patients progressed, Dr. Houot said.
“The follow-up of the TRANSCEND study is still very short – the median is 5.9 months – so we don’t have survival data yet for these patients,” he noted.
Still, the efficacy in these studies is excellent, particularly considering the challenges of treating MCL patients who relapse or are refractory after BTKi treatment, he said, noting that most patients in both studies had poor prognostic factors.
Toxicities in both studies were similar to those seen in studies of patients with aggressive B-cell lymphomas who were treated with these drugs, he added.
“Longer follow-up is needed to better evaluate long-term efficacy,” he said, concluding that the results nonetheless “support evaluation of CAR T-cell therapy earlier in the therapeutic strategy of mantle cell lymphoma.”
Dr. Houot reported having no disclosures.
FROM CART21
CDC panel: Pause of J&J COVID-19 vaccine to remain for now
The Advisory Committee on Immunization Practices decided there was not adequate information to change again recommend use of the Johnson & Johnson vaccine.
The committee’s decision comes the day after the CDC and Food and Drug Administration recommended that J&J injections be paused after reports of rare, but serious types of blood clots in six patients among the 6.8 million people who had received the J&J vaccine in the United States.
A member of the committee, Beth Bell, MD, said: “I do not want to be sending a message that there is some huge concern here on a different order of magnitude than any other vaccine safety signals that we evaluate. And I don’t want to send a message that there is something fundamentally wrong with the vaccine because that also I don’t agree with.”
At the end of the 4-hour meeting, ACIP members decided to call a meeting in 1 or 2 weeks and evaluate more safety data, specifically reports of people who have received the J&J vaccine in the past 2 weeks.
Some, however, pointed out that delaying a decision could have substantial consequences as well in terms of unused vaccine doses and public confidence.
Committee member Camiile Kotton, MD, described the pause as “devastating.”
“Putting this vaccine on pause for those of us that are frontline health care workers has really been devastating,” she said. “I agree in general that we don’t have enough data to make a decision at this time but we were planning on using this vaccine in the state of Massachusetts for people who were homebound and otherwise not able to get a vaccine. We were planning on using it for our vulnerable inpatient population often with many comorbidities and at high risk for disease but haven’t been able to get vaccinated otherwise.”
Pausing the one-and-done vaccine that doesn’t have the significant refrigeration requirements of the others “is a significant loss,” she said.
What is known, not known
Sara Oliver, MD, who leads the COVID-19 Vaccines ACIP Work Group, summarized what is known and unknown about the blood clots.
Among the six cases of cerebral venous sinus thrombosis reported to the Vaccine Adverse Event Reporting System after the J&J shot, all were women aged 18-48 years and all developed the clots 6-13 days after receiving the vaccine.
No cases of these clots have been reported from either the Pfizer or Moderna shots, she noted.
In the United States, the two mRNA vaccine alternatives – the Moderna and Pfizer vaccines – are available “and based on current projections supply of both vaccines are expected to be relatively stable in the near future,” she said.
She said 14 million doses of Pfizer and Moderna are expected each week in the United States and J&J vaccines makes up less than 5% of vaccines administered in the country.
Approximately 13 million J&J doses are available to order or are already at administration sites, she said.
But much more is unknown, she said.
“There may be more cases identified in the coming days to weeks,” Dr. Oliver said, referring back to the average time from vaccination to symptom onset.
Scott Ratzan, MD, editor-in-chief of the Journal of Health Communication: International Perspectives and executive director of Business Partners to CONVINCE (BP2C), a global network of employers that promotes COVID-19 vaccination among employees, suppliers, and customers, applauded ACIP’s delay on making a decision.
Dr. Ratzan, who watched the deliberations online, said in an interview the decision “shows an admirable abundance of caution in the distribution of COVID-19 vaccines.”
“Unfortunately,” he said, “the pause also worsens the existing and pervasive vaccine hesitancy issue.
“We need a rational strategy regarding who should or should not get the J&J/Janssen vaccine since these rare adverse events appear to affect a particular group of people, females aged 18-48. It is essential that we build vaccine confidence and retain the option of using this vaccine for people who are not in this risk group.”
He pointed out there are safety red flags with the Pfizer and Moderna COVID-19 vaccines.
“We should feel reassured about the process of ensuring vaccine safety as the FDA and CDC have quickly addressed risk and shared the data transparently of the J&J vaccine and taken appropriate action,” he said.
ACIP’s executive secretary, Amanda Cohn, MD, said the date for the next meeting would be set by April 16.
A version of this article first appeared on WebMD.com.
The Advisory Committee on Immunization Practices decided there was not adequate information to change again recommend use of the Johnson & Johnson vaccine.
The committee’s decision comes the day after the CDC and Food and Drug Administration recommended that J&J injections be paused after reports of rare, but serious types of blood clots in six patients among the 6.8 million people who had received the J&J vaccine in the United States.
A member of the committee, Beth Bell, MD, said: “I do not want to be sending a message that there is some huge concern here on a different order of magnitude than any other vaccine safety signals that we evaluate. And I don’t want to send a message that there is something fundamentally wrong with the vaccine because that also I don’t agree with.”
At the end of the 4-hour meeting, ACIP members decided to call a meeting in 1 or 2 weeks and evaluate more safety data, specifically reports of people who have received the J&J vaccine in the past 2 weeks.
Some, however, pointed out that delaying a decision could have substantial consequences as well in terms of unused vaccine doses and public confidence.
Committee member Camiile Kotton, MD, described the pause as “devastating.”
“Putting this vaccine on pause for those of us that are frontline health care workers has really been devastating,” she said. “I agree in general that we don’t have enough data to make a decision at this time but we were planning on using this vaccine in the state of Massachusetts for people who were homebound and otherwise not able to get a vaccine. We were planning on using it for our vulnerable inpatient population often with many comorbidities and at high risk for disease but haven’t been able to get vaccinated otherwise.”
Pausing the one-and-done vaccine that doesn’t have the significant refrigeration requirements of the others “is a significant loss,” she said.
What is known, not known
Sara Oliver, MD, who leads the COVID-19 Vaccines ACIP Work Group, summarized what is known and unknown about the blood clots.
Among the six cases of cerebral venous sinus thrombosis reported to the Vaccine Adverse Event Reporting System after the J&J shot, all were women aged 18-48 years and all developed the clots 6-13 days after receiving the vaccine.
No cases of these clots have been reported from either the Pfizer or Moderna shots, she noted.
In the United States, the two mRNA vaccine alternatives – the Moderna and Pfizer vaccines – are available “and based on current projections supply of both vaccines are expected to be relatively stable in the near future,” she said.
She said 14 million doses of Pfizer and Moderna are expected each week in the United States and J&J vaccines makes up less than 5% of vaccines administered in the country.
Approximately 13 million J&J doses are available to order or are already at administration sites, she said.
But much more is unknown, she said.
“There may be more cases identified in the coming days to weeks,” Dr. Oliver said, referring back to the average time from vaccination to symptom onset.
Scott Ratzan, MD, editor-in-chief of the Journal of Health Communication: International Perspectives and executive director of Business Partners to CONVINCE (BP2C), a global network of employers that promotes COVID-19 vaccination among employees, suppliers, and customers, applauded ACIP’s delay on making a decision.
Dr. Ratzan, who watched the deliberations online, said in an interview the decision “shows an admirable abundance of caution in the distribution of COVID-19 vaccines.”
“Unfortunately,” he said, “the pause also worsens the existing and pervasive vaccine hesitancy issue.
“We need a rational strategy regarding who should or should not get the J&J/Janssen vaccine since these rare adverse events appear to affect a particular group of people, females aged 18-48. It is essential that we build vaccine confidence and retain the option of using this vaccine for people who are not in this risk group.”
He pointed out there are safety red flags with the Pfizer and Moderna COVID-19 vaccines.
“We should feel reassured about the process of ensuring vaccine safety as the FDA and CDC have quickly addressed risk and shared the data transparently of the J&J vaccine and taken appropriate action,” he said.
ACIP’s executive secretary, Amanda Cohn, MD, said the date for the next meeting would be set by April 16.
A version of this article first appeared on WebMD.com.
The Advisory Committee on Immunization Practices decided there was not adequate information to change again recommend use of the Johnson & Johnson vaccine.
The committee’s decision comes the day after the CDC and Food and Drug Administration recommended that J&J injections be paused after reports of rare, but serious types of blood clots in six patients among the 6.8 million people who had received the J&J vaccine in the United States.
A member of the committee, Beth Bell, MD, said: “I do not want to be sending a message that there is some huge concern here on a different order of magnitude than any other vaccine safety signals that we evaluate. And I don’t want to send a message that there is something fundamentally wrong with the vaccine because that also I don’t agree with.”
At the end of the 4-hour meeting, ACIP members decided to call a meeting in 1 or 2 weeks and evaluate more safety data, specifically reports of people who have received the J&J vaccine in the past 2 weeks.
Some, however, pointed out that delaying a decision could have substantial consequences as well in terms of unused vaccine doses and public confidence.
Committee member Camiile Kotton, MD, described the pause as “devastating.”
“Putting this vaccine on pause for those of us that are frontline health care workers has really been devastating,” she said. “I agree in general that we don’t have enough data to make a decision at this time but we were planning on using this vaccine in the state of Massachusetts for people who were homebound and otherwise not able to get a vaccine. We were planning on using it for our vulnerable inpatient population often with many comorbidities and at high risk for disease but haven’t been able to get vaccinated otherwise.”
Pausing the one-and-done vaccine that doesn’t have the significant refrigeration requirements of the others “is a significant loss,” she said.
What is known, not known
Sara Oliver, MD, who leads the COVID-19 Vaccines ACIP Work Group, summarized what is known and unknown about the blood clots.
Among the six cases of cerebral venous sinus thrombosis reported to the Vaccine Adverse Event Reporting System after the J&J shot, all were women aged 18-48 years and all developed the clots 6-13 days after receiving the vaccine.
No cases of these clots have been reported from either the Pfizer or Moderna shots, she noted.
In the United States, the two mRNA vaccine alternatives – the Moderna and Pfizer vaccines – are available “and based on current projections supply of both vaccines are expected to be relatively stable in the near future,” she said.
She said 14 million doses of Pfizer and Moderna are expected each week in the United States and J&J vaccines makes up less than 5% of vaccines administered in the country.
Approximately 13 million J&J doses are available to order or are already at administration sites, she said.
But much more is unknown, she said.
“There may be more cases identified in the coming days to weeks,” Dr. Oliver said, referring back to the average time from vaccination to symptom onset.
Scott Ratzan, MD, editor-in-chief of the Journal of Health Communication: International Perspectives and executive director of Business Partners to CONVINCE (BP2C), a global network of employers that promotes COVID-19 vaccination among employees, suppliers, and customers, applauded ACIP’s delay on making a decision.
Dr. Ratzan, who watched the deliberations online, said in an interview the decision “shows an admirable abundance of caution in the distribution of COVID-19 vaccines.”
“Unfortunately,” he said, “the pause also worsens the existing and pervasive vaccine hesitancy issue.
“We need a rational strategy regarding who should or should not get the J&J/Janssen vaccine since these rare adverse events appear to affect a particular group of people, females aged 18-48. It is essential that we build vaccine confidence and retain the option of using this vaccine for people who are not in this risk group.”
He pointed out there are safety red flags with the Pfizer and Moderna COVID-19 vaccines.
“We should feel reassured about the process of ensuring vaccine safety as the FDA and CDC have quickly addressed risk and shared the data transparently of the J&J vaccine and taken appropriate action,” he said.
ACIP’s executive secretary, Amanda Cohn, MD, said the date for the next meeting would be set by April 16.
A version of this article first appeared on WebMD.com.
How to counsel worried patients about the J&J vaccine news
On April 13, the Centers for Disease Control and Prevention and the Food and Drug Administration issued a joint statement recommending a pause in Johnson & Johnson vaccine administration, pending review of six reported U.S. cases of a rare and severe type of blood clot occurring after receiving the Johnson & Johnson vaccine. To date, more than 6.8 million doses of that vaccine have been given in the United States, so at this point the rate of detected cases of this problem is less than one in a million.
The six cases occurred in women aged 18-48 years, and symptoms occurred 6-13 days after vaccination. In these cases, cerebral venous sinus thrombosis was seen in addition to thrombocytopenia.
Physicians may receive calls from concerned patients who have received a COVID vaccine. However, more than 95% of the vaccine administrations in the United States to date have been the Pfizer and Moderna messenger RNA vaccines. No association between these vaccines and blood clots has been detected. Also, these six cases occurred within 2 weeks of Johnson & Johnson vaccination, so even among those receiving the Johnson & Johnson vaccine, those who are more than 3 weeks out from their vaccination have no need for concern regarding this rare complication.
Physicians should counsel those who have received the Johnson & Johnson vaccine less than 3 weeks ago to watch for easy bruising, gum bleeding, nose bleeds, leg or arm pain or swelling, severe headache or abdominal pain, shortness of breath, or chest pain. If they notice one or more of those symptoms, they should seek medical attention.
The Centers for Disease Control and Prevention will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the six U.S. cases of the Johnson & Johnson vaccine and determine their significance.
Several cases of unusual thromboses and thrombocytopenia have been detected after the Oxford AstraZeneca vaccine, which uses the same adenovirus vector technology as the Johnson & Johnson vaccine, but which is not authorized for use in the United States. The Oxford AstraZeneca vaccine uses a recombinant deficient chimpanzee adenovirus to deliver the message to cells to produce antibody against the SARS-CoV-2 spike protein. The Johnson & Johnson vaccine uses a recombinant deficient human adenovirus to deliver this same message.
Two recent reports in the New England Journal of Medicine have reported on thrombosis and thrombocytopenia after the Oxford AstraZeneca vaccine in Europe. Both of these reports identified high levels of IgG antibodies to platelet factor 4–polyanion complexes, similar to the mechanism of heparin-induced thrombocytopenia. The term vaccine-induced immune thrombocytopenia was proposed for this phenomenon. Treatment of this condition involves administration of intravenous immunoglobulin and nonheparin anticoagulants. Recent updates from the World Health Organization report that 169 cases of cerebral venous sinus thrombosis and 53 of splanchnic venous thrombosis occurred after 34 million doses of the Oxford AstraZeneca vaccine was administered in the European Union and United Kingdom.
While this pause in Johnson & Johnson vaccination is disappointing news amid increased cases in parts of the country, the Johnson & Johnson vaccines make up less than 5% of the U.S. vaccine doses administered to date. According to the CDC, more than 122 million Americans have received at least one dose and more than 75 million are fully vaccinated.
Dr. Patterson has received an honorarium from Pfizer for an antifungal symposium and is a subinvestigator for the Novavax vaccine. Her spouse served as a consultant for SCYNEXIS, as a speaker for Gilead Sciences and Basilea, and has received a research grant from the National Institutes of Health for the ACTT remdesivir trial.
A version of this article first appeared on Medscape.com.
On April 13, the Centers for Disease Control and Prevention and the Food and Drug Administration issued a joint statement recommending a pause in Johnson & Johnson vaccine administration, pending review of six reported U.S. cases of a rare and severe type of blood clot occurring after receiving the Johnson & Johnson vaccine. To date, more than 6.8 million doses of that vaccine have been given in the United States, so at this point the rate of detected cases of this problem is less than one in a million.
The six cases occurred in women aged 18-48 years, and symptoms occurred 6-13 days after vaccination. In these cases, cerebral venous sinus thrombosis was seen in addition to thrombocytopenia.
Physicians may receive calls from concerned patients who have received a COVID vaccine. However, more than 95% of the vaccine administrations in the United States to date have been the Pfizer and Moderna messenger RNA vaccines. No association between these vaccines and blood clots has been detected. Also, these six cases occurred within 2 weeks of Johnson & Johnson vaccination, so even among those receiving the Johnson & Johnson vaccine, those who are more than 3 weeks out from their vaccination have no need for concern regarding this rare complication.
Physicians should counsel those who have received the Johnson & Johnson vaccine less than 3 weeks ago to watch for easy bruising, gum bleeding, nose bleeds, leg or arm pain or swelling, severe headache or abdominal pain, shortness of breath, or chest pain. If they notice one or more of those symptoms, they should seek medical attention.
The Centers for Disease Control and Prevention will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the six U.S. cases of the Johnson & Johnson vaccine and determine their significance.
Several cases of unusual thromboses and thrombocytopenia have been detected after the Oxford AstraZeneca vaccine, which uses the same adenovirus vector technology as the Johnson & Johnson vaccine, but which is not authorized for use in the United States. The Oxford AstraZeneca vaccine uses a recombinant deficient chimpanzee adenovirus to deliver the message to cells to produce antibody against the SARS-CoV-2 spike protein. The Johnson & Johnson vaccine uses a recombinant deficient human adenovirus to deliver this same message.
Two recent reports in the New England Journal of Medicine have reported on thrombosis and thrombocytopenia after the Oxford AstraZeneca vaccine in Europe. Both of these reports identified high levels of IgG antibodies to platelet factor 4–polyanion complexes, similar to the mechanism of heparin-induced thrombocytopenia. The term vaccine-induced immune thrombocytopenia was proposed for this phenomenon. Treatment of this condition involves administration of intravenous immunoglobulin and nonheparin anticoagulants. Recent updates from the World Health Organization report that 169 cases of cerebral venous sinus thrombosis and 53 of splanchnic venous thrombosis occurred after 34 million doses of the Oxford AstraZeneca vaccine was administered in the European Union and United Kingdom.
While this pause in Johnson & Johnson vaccination is disappointing news amid increased cases in parts of the country, the Johnson & Johnson vaccines make up less than 5% of the U.S. vaccine doses administered to date. According to the CDC, more than 122 million Americans have received at least one dose and more than 75 million are fully vaccinated.
Dr. Patterson has received an honorarium from Pfizer for an antifungal symposium and is a subinvestigator for the Novavax vaccine. Her spouse served as a consultant for SCYNEXIS, as a speaker for Gilead Sciences and Basilea, and has received a research grant from the National Institutes of Health for the ACTT remdesivir trial.
A version of this article first appeared on Medscape.com.
On April 13, the Centers for Disease Control and Prevention and the Food and Drug Administration issued a joint statement recommending a pause in Johnson & Johnson vaccine administration, pending review of six reported U.S. cases of a rare and severe type of blood clot occurring after receiving the Johnson & Johnson vaccine. To date, more than 6.8 million doses of that vaccine have been given in the United States, so at this point the rate of detected cases of this problem is less than one in a million.
The six cases occurred in women aged 18-48 years, and symptoms occurred 6-13 days after vaccination. In these cases, cerebral venous sinus thrombosis was seen in addition to thrombocytopenia.
Physicians may receive calls from concerned patients who have received a COVID vaccine. However, more than 95% of the vaccine administrations in the United States to date have been the Pfizer and Moderna messenger RNA vaccines. No association between these vaccines and blood clots has been detected. Also, these six cases occurred within 2 weeks of Johnson & Johnson vaccination, so even among those receiving the Johnson & Johnson vaccine, those who are more than 3 weeks out from their vaccination have no need for concern regarding this rare complication.
Physicians should counsel those who have received the Johnson & Johnson vaccine less than 3 weeks ago to watch for easy bruising, gum bleeding, nose bleeds, leg or arm pain or swelling, severe headache or abdominal pain, shortness of breath, or chest pain. If they notice one or more of those symptoms, they should seek medical attention.
The Centers for Disease Control and Prevention will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the six U.S. cases of the Johnson & Johnson vaccine and determine their significance.
Several cases of unusual thromboses and thrombocytopenia have been detected after the Oxford AstraZeneca vaccine, which uses the same adenovirus vector technology as the Johnson & Johnson vaccine, but which is not authorized for use in the United States. The Oxford AstraZeneca vaccine uses a recombinant deficient chimpanzee adenovirus to deliver the message to cells to produce antibody against the SARS-CoV-2 spike protein. The Johnson & Johnson vaccine uses a recombinant deficient human adenovirus to deliver this same message.
Two recent reports in the New England Journal of Medicine have reported on thrombosis and thrombocytopenia after the Oxford AstraZeneca vaccine in Europe. Both of these reports identified high levels of IgG antibodies to platelet factor 4–polyanion complexes, similar to the mechanism of heparin-induced thrombocytopenia. The term vaccine-induced immune thrombocytopenia was proposed for this phenomenon. Treatment of this condition involves administration of intravenous immunoglobulin and nonheparin anticoagulants. Recent updates from the World Health Organization report that 169 cases of cerebral venous sinus thrombosis and 53 of splanchnic venous thrombosis occurred after 34 million doses of the Oxford AstraZeneca vaccine was administered in the European Union and United Kingdom.
While this pause in Johnson & Johnson vaccination is disappointing news amid increased cases in parts of the country, the Johnson & Johnson vaccines make up less than 5% of the U.S. vaccine doses administered to date. According to the CDC, more than 122 million Americans have received at least one dose and more than 75 million are fully vaccinated.
Dr. Patterson has received an honorarium from Pfizer for an antifungal symposium and is a subinvestigator for the Novavax vaccine. Her spouse served as a consultant for SCYNEXIS, as a speaker for Gilead Sciences and Basilea, and has received a research grant from the National Institutes of Health for the ACTT remdesivir trial.
A version of this article first appeared on Medscape.com.
COVID-19 vaccine failure in patients with blood cancers
COVID vaccines do not work well for patients with hematologic malignancies, new data suggest.
A small study involving 67 such patients shows that nearly half did not produce antibodies and were therefore still at risk of contracting COVID-19, even though they had all received both doses of one of the new mRNA COVID vaccines (Moderna or Pfizer).
“[This] is in stark contrast with the results of phase 1 mRNA vaccine immunogenicity trials, in which robust antibody responses were seen in essentially 100% of participants,” said the authors, led by Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at the University of Pittsburgh Medical Center’s Hillman Cancer Center.
“Clinicians caring for patients with hematological malignancies and other immunocompromising conditions should be aware of the possibility of COVID-19 vaccine failure,” they emphasized.
“It’s critically important for these patients to be aware of their continued risk [for SARS-CoV-2 infection] and to seek prompt medical attention if they have COVID-19 symptoms, even after vaccination,” Dr. Agha said in a statement.
The study was published online on April 9 as preprint in medRxiv and has not yet undergone peer review.
Antibody responses
The authors analyzed responses in a group of 67 patients who had a hematologic malignancy, including chronic lymphocytic leukemia (CLL), lymphoma, and multiple myeloma. Approximately 45% of the patients were receiving therapy for their cancer at the time of vaccination; the rest were under observation.
All patients received two doses of an mRNA COVID vaccine and so were considered to be fully vaccinated.
Antibody responses for these fully vaccinated patients were then analyzed. The median duration between receipt of the second dose of the vaccine and the antibody test was 23 days.
“In total ... 46.3% ... had a negative antibody result after vaccination and were therefore considered to be vaccine nonresponders,” the authors reported.
The worst responses occurred in patients with CLL, of whom only 23% produced measurable antibodies to either vaccine, although approximately 70% of these patients were not receiving any form of cancer therapy at the time of vaccination.
Older patients were more likely not to have a response to either vaccine compared with younger patients, the investigators added.
In contrast, gender, immunoglobulin G levels, the number of days between the second dose and the measurement of antibodies, and status of cancer therapy did not differ among patients who had a response to the vaccines and those who did not.
“Our findings underscore the importance of adherence to nonpharmaceutical interventions to prevent COVID-19 in hematological malignancy patients,” the authors wrote. This is particularly important, given the fact that among patients with hematologic malignancies who become infected with SARS-CoV-2, the mortality rate is in excess of 30%.
Moreover, among such patients, viral shedding may be prolonged, often lasting several months. As such, “these patients should be advised to wear masks and observe social distancing regardless of vaccination status,” the investigators advised.
As of March 2021, guidance from the Centers for Disease Control and Prevention has allowed gatherings of unmasked people who have been vaccinated and of those at low risk for COVID-19 who have not yet been vaccinated. “As we see more national guidance allowing for unmasked gatherings among vaccinated people, clinicians should counsel their immunocompromised patients about the possibility that COVID-19 vaccines may not fully protect them against SARS-CoV-2,” coauthor Ghady Haidar, MD, assistant professor of medicine at the University of Pittsburgh, said in a statement.
“Our results show that the odds of the vaccine producing an antibody response in people with hematologic malignancies are the equivalent of a coin flip,” he said.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID vaccines do not work well for patients with hematologic malignancies, new data suggest.
A small study involving 67 such patients shows that nearly half did not produce antibodies and were therefore still at risk of contracting COVID-19, even though they had all received both doses of one of the new mRNA COVID vaccines (Moderna or Pfizer).
“[This] is in stark contrast with the results of phase 1 mRNA vaccine immunogenicity trials, in which robust antibody responses were seen in essentially 100% of participants,” said the authors, led by Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at the University of Pittsburgh Medical Center’s Hillman Cancer Center.
“Clinicians caring for patients with hematological malignancies and other immunocompromising conditions should be aware of the possibility of COVID-19 vaccine failure,” they emphasized.
“It’s critically important for these patients to be aware of their continued risk [for SARS-CoV-2 infection] and to seek prompt medical attention if they have COVID-19 symptoms, even after vaccination,” Dr. Agha said in a statement.
The study was published online on April 9 as preprint in medRxiv and has not yet undergone peer review.
Antibody responses
The authors analyzed responses in a group of 67 patients who had a hematologic malignancy, including chronic lymphocytic leukemia (CLL), lymphoma, and multiple myeloma. Approximately 45% of the patients were receiving therapy for their cancer at the time of vaccination; the rest were under observation.
All patients received two doses of an mRNA COVID vaccine and so were considered to be fully vaccinated.
Antibody responses for these fully vaccinated patients were then analyzed. The median duration between receipt of the second dose of the vaccine and the antibody test was 23 days.
“In total ... 46.3% ... had a negative antibody result after vaccination and were therefore considered to be vaccine nonresponders,” the authors reported.
The worst responses occurred in patients with CLL, of whom only 23% produced measurable antibodies to either vaccine, although approximately 70% of these patients were not receiving any form of cancer therapy at the time of vaccination.
Older patients were more likely not to have a response to either vaccine compared with younger patients, the investigators added.
In contrast, gender, immunoglobulin G levels, the number of days between the second dose and the measurement of antibodies, and status of cancer therapy did not differ among patients who had a response to the vaccines and those who did not.
“Our findings underscore the importance of adherence to nonpharmaceutical interventions to prevent COVID-19 in hematological malignancy patients,” the authors wrote. This is particularly important, given the fact that among patients with hematologic malignancies who become infected with SARS-CoV-2, the mortality rate is in excess of 30%.
Moreover, among such patients, viral shedding may be prolonged, often lasting several months. As such, “these patients should be advised to wear masks and observe social distancing regardless of vaccination status,” the investigators advised.
As of March 2021, guidance from the Centers for Disease Control and Prevention has allowed gatherings of unmasked people who have been vaccinated and of those at low risk for COVID-19 who have not yet been vaccinated. “As we see more national guidance allowing for unmasked gatherings among vaccinated people, clinicians should counsel their immunocompromised patients about the possibility that COVID-19 vaccines may not fully protect them against SARS-CoV-2,” coauthor Ghady Haidar, MD, assistant professor of medicine at the University of Pittsburgh, said in a statement.
“Our results show that the odds of the vaccine producing an antibody response in people with hematologic malignancies are the equivalent of a coin flip,” he said.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
COVID vaccines do not work well for patients with hematologic malignancies, new data suggest.
A small study involving 67 such patients shows that nearly half did not produce antibodies and were therefore still at risk of contracting COVID-19, even though they had all received both doses of one of the new mRNA COVID vaccines (Moderna or Pfizer).
“[This] is in stark contrast with the results of phase 1 mRNA vaccine immunogenicity trials, in which robust antibody responses were seen in essentially 100% of participants,” said the authors, led by Mounzer Agha, MD, director of the Mario Lemieux Center for Blood Cancers at the University of Pittsburgh Medical Center’s Hillman Cancer Center.
“Clinicians caring for patients with hematological malignancies and other immunocompromising conditions should be aware of the possibility of COVID-19 vaccine failure,” they emphasized.
“It’s critically important for these patients to be aware of their continued risk [for SARS-CoV-2 infection] and to seek prompt medical attention if they have COVID-19 symptoms, even after vaccination,” Dr. Agha said in a statement.
The study was published online on April 9 as preprint in medRxiv and has not yet undergone peer review.
Antibody responses
The authors analyzed responses in a group of 67 patients who had a hematologic malignancy, including chronic lymphocytic leukemia (CLL), lymphoma, and multiple myeloma. Approximately 45% of the patients were receiving therapy for their cancer at the time of vaccination; the rest were under observation.
All patients received two doses of an mRNA COVID vaccine and so were considered to be fully vaccinated.
Antibody responses for these fully vaccinated patients were then analyzed. The median duration between receipt of the second dose of the vaccine and the antibody test was 23 days.
“In total ... 46.3% ... had a negative antibody result after vaccination and were therefore considered to be vaccine nonresponders,” the authors reported.
The worst responses occurred in patients with CLL, of whom only 23% produced measurable antibodies to either vaccine, although approximately 70% of these patients were not receiving any form of cancer therapy at the time of vaccination.
Older patients were more likely not to have a response to either vaccine compared with younger patients, the investigators added.
In contrast, gender, immunoglobulin G levels, the number of days between the second dose and the measurement of antibodies, and status of cancer therapy did not differ among patients who had a response to the vaccines and those who did not.
“Our findings underscore the importance of adherence to nonpharmaceutical interventions to prevent COVID-19 in hematological malignancy patients,” the authors wrote. This is particularly important, given the fact that among patients with hematologic malignancies who become infected with SARS-CoV-2, the mortality rate is in excess of 30%.
Moreover, among such patients, viral shedding may be prolonged, often lasting several months. As such, “these patients should be advised to wear masks and observe social distancing regardless of vaccination status,” the investigators advised.
As of March 2021, guidance from the Centers for Disease Control and Prevention has allowed gatherings of unmasked people who have been vaccinated and of those at low risk for COVID-19 who have not yet been vaccinated. “As we see more national guidance allowing for unmasked gatherings among vaccinated people, clinicians should counsel their immunocompromised patients about the possibility that COVID-19 vaccines may not fully protect them against SARS-CoV-2,” coauthor Ghady Haidar, MD, assistant professor of medicine at the University of Pittsburgh, said in a statement.
“Our results show that the odds of the vaccine producing an antibody response in people with hematologic malignancies are the equivalent of a coin flip,” he said.
The authors have disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Data about COVID-19-related skin manifestations in children continue to emerge
Two and stratifying children at risk for serious, systemic illness due to the virus.
In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).
“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.
“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”
In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).
Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).
The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.
“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”
Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”
In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).
In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.
The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”
At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.
Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.
The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.
“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.
“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.
“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”
The researchers reported having no financial disclosures.
Two and stratifying children at risk for serious, systemic illness due to the virus.
In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).
“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.
“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”
In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).
Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).
The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.
“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”
Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”
In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).
In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.
The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”
At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.
Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.
The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.
“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.
“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.
“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”
The researchers reported having no financial disclosures.
Two and stratifying children at risk for serious, systemic illness due to the virus.
In a single-center descriptive study carried out over a 9-month period, researchers in Madrid found that of 50 hospitalized children infected with COVID-19, 21 (42%) had mucocutaneous symptoms, most commonly exanthem, followed by conjunctival hyperemia without secretion and red cracked lips or strawberry tongue. In addition, 18 (36%) fulfilled criteria for Multisystem Inflammatory Syndrome in Children (MIS-C).
“Based on findings in adult patients, the skin manifestations of COVID-19 have been classified under five categories: acral pseudo-chilblain, vesicular eruptions, urticarial lesions, maculopapular eruptions, and livedo or necrosis,” David Andina-Martinez, MD, of Hospital Infantil Universitario Niño Jesús, Madrid, and colleagues wrote in the study, which was published online on April 2 in the Journal of the American Academy of Dermatology.
“Chilblain lesions in healthy children and adolescents have received much attention; these lesions resolve without complications after a few weeks,” they added. “Besides, other cutaneous manifestations of COVID-19 in children have been the matter of case reports or small case series. Nevertheless, the mucocutaneous manifestations in hospitalized children infected with SARS-CoV-2 and their implications on the clinical course have not yet been extensively described.”
In an effort to describe the mucocutaneous manifestations in children hospitalized for COVID-19, the researchers evaluated 50 children up to 18 years of age who were admitted between March 1 and Nov. 30, 2020, to Hospital Infantil Universitario Niño Jesús, which was designated as a pediatric reference center during the peak of the pandemic. The main reasons for admission were respiratory illness (40%) and MIS-C (40%).
Of the 50 patients, 44 (88%) had a positive RT-PCR for SARS-CoV-2 and 6 (12%) met clinical suspicion criteria and had a negative RT-PCR with a positive IgG serology. In 34 patients (68%), a close contact with a suspected or confirmed case of COVID-19 was referred, while the source of the infection remained unknown in the remaining 16 patients (32%).
The researchers reported that 21 patients (42%) had mucocutaneous symptoms, most commonly maculopapular exanthem (86%), conjunctival hyperemia (81%), and red cracked lips or strawberry tongue (43%). In addition, 18 of the 21 patients (86%) fulfilled criteria for MIS-C.
“A tricky thing about MIS-C is that it often manifests 4-5 weeks after a child had COVID-19,” said Christine Ko, MD, professor of dermatology and pathology at Yale University, New Haven, Conn., who was asked to comment on the study. “MIS-C is associated with characteristic bright red lips and a red tongue that might resemble a strawberry. Such oral findings should prompt rapid evaluation for other signs and symptoms. There can be redness of the eyes or other more nonspecific skin findings (large or small areas of redness on the trunk or limbs, sometimes with surface change), but more importantly, fever, a rapid heartbeat, diarrhea, or breathing issues. The risk with MIS-C is a rapid decline in a child’s health, with admission to an intensive care unit.”
Dr. Andina-Martinez and his colleagues also contrast the skin findings of MIS-C, which are not generally on the hands or feet, with the so-called “COVID toe” or finger phenomenon, which has also been associated with SARS-CoV-2, particularly in children. “Only one of the patients in this series had skin involvement of a finger, and it only appeared after recovery from MIS-C,” Dr. Ko noted. “Distinguishing COVID toes from MIS-C is important, as COVID toes has a very good outcome, while MIS-C can have severe consequences, including protracted heart disease.”
In other findings, patients who presented with mucocutaneous signs tended to be older than those without skin signs and they presented at the emergency department with poor general status and extreme tachycardia. They also had higher C-reactive protein and D-dimer levels and lower lymphocyte counts and faced a more than a 10-fold increased risk of being admitted to the PICU, compared with patients who did not have skin signs (OR, 10.24; P = .003).
In a separate study published online on April 7 in JAMA Dermatology, Zachary E. Holcomb, MD, of the combined dermatology residency program at Massachusetts General Hospital, Boston, and colleagues presented what is believed to be the first case report of reactive infectious mucocutaneous eruption (RIME) triggered by SARS-CoV-2. RIME is the preferred term for pediatric patients who present with mucositis and rash (often a scant or even absent skin eruption) triggered by various infectious agents.
The patient, a 17-year-old male, presented to the emergency department with 3 days of mouth pain and nonpainful penile erosions. “One week prior, he experienced transient anosmia and ageusia that had since spontaneously resolved,” the researchers wrote. “At that time, he was tested for SARS-CoV-2 infection via nasopharyngeal polymerase chain reaction (PCR), the results of which were positive.”
At presentation, the patient had no fever, his vital signs were normal, and the physical exam revealed shallow erosions of the vermilion lips and hard palate, circumferential erythematous erosions of the periurethral glans penis, and five small vesicles on the trunk and upper extremities. Serum analysis revealed a normal white blood cell count with mild absolute lymphopenia, slightly elevated creatinine level, normal liver function, slightly elevated C-reactive protein level, and normal ferritin level.
Dr. Holcomb and colleagues made a diagnosis of SARS-CoV-2–associated RIME based on microbiological results, which revealed positive repeated SARS-CoV-2 nasopharyngeal PCR and negative nasopharyngeal PCR testing for Mycoplasma pneumoniae, adenovirus, Chlamydophila pneumoniae, human metapneumovirus, influenza A/B, parainfluenza 1 to 4, rhinovirus, and respiratory syncytial virus. In addition, titers of Mycoplasma pneumoniae IgM levels were negative, but Mycoplasma pneumoniae IgG levels were elevated.
The lesions resolved with 60 mg of oral prednisone taken daily for 4 days. A recurrence of oral mucositis 3 months later responded to 80 mg oral prednisone taken daily for 6 days.
“It’s not surprising that SARS-CoV-2 is yet another trigger for RIME,” said Anna Yasmine Kirkorian, MD, chief of the division of dermatology at Children’s National Hospital, Washington, who was asked to comment about the case report.
“The take-home message is for clinicians to be aware of this association and distinguish these patients from those with MIS-C, because patients with MIS-C require monitoring and urgent systemic treatment. RIME and MIS-C may potentially be distinguished clinically based on the nature of the mucositis (hemorrhagic and erosive in RIME, dry, cracked lips with ‘strawberry tongue’ in MIS-C) but more importantly patients with RIME lack laboratory evidence of severe systemic inflammation,” such as ESR, CRP, or ferritin, she said.
“A final interesting point in this article was the recurrence of mucositis in this patient, which could mean that recurrent mucositis/recurrent RIME might be yet another manifestation of ‘long-COVID’ (now called post-Acute Sequelae of SARS-CoV-2 infection) in some patients,” Dr. Kirkorian added. She noted that the American Academy of Dermatology–International League of Dermatologic Societies COVID-19 Dermatology Registry and articles like these “provide invaluable ‘hot off the presses’ information for clinicians who are facing the protean manifestations of a novel viral epidemic.”
The researchers reported having no financial disclosures.
Personalized cancer vaccine shows early promise across tumor types
The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.
At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.
Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.
“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”
With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
Creating a personalized vaccine
The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.
Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.
OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
Vaccine administration
The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.
“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .
“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
Feasibility, safety, and immunogenicity
PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.
Eleven patients received all 10 intended doses, and two patients received at least 8 doses.
“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.
Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.
Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.
Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
Survival and subsequent therapy
At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.
Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.
Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.
“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.
Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.
The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.
The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.
At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.
Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.
“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”
With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
Creating a personalized vaccine
The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.
Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.
OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
Vaccine administration
The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.
“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .
“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
Feasibility, safety, and immunogenicity
PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.
Eleven patients received all 10 intended doses, and two patients received at least 8 doses.
“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.
Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.
Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.
Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
Survival and subsequent therapy
At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.
Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.
Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.
“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.
Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.
The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.
The vaccine, PGV-001, was given to 13 patients with solid tumors or multiple myeloma who had a high risk of recurrence after surgery or autologous stem cell transplant.
At last follow-up, four patients were still alive without evidence of disease and had not received subsequent therapy, four were alive and receiving therapy, three had died, and two were lost to follow-up.
Thomas Marron, MD, PhD , of Mount Sinai in New York presented these results in a poster at the American Association for Cancer Research Annual Meeting 2021: Week 1 ( Abstract LB048 ). Data in the abstract differ from the data presented.
“While cancer immunotherapy has revolutionized the treatment of cancer, we know that the majority of patients fail to achieve significant clinical response,” Dr. Marron said during his presentation. “One reason for this may be due to lack of preexisting primed T-cell response needed for PD-1 blockade to have a significant effect. To address this, personalized neoantigen vaccines may help prime an improved immune response against tumor cells.”
With this in mind, Dr. Marron and colleagues developed PGV-001, a vaccine consisting of patient-specific synthetic neoantigen peptides given to patients in the adjuvant setting.
Creating a personalized vaccine
The researchers synthesized PGV-001 for 15 patients with advanced malignancies. The patients first underwent tumor and germline DNA sequencing as well as HLA typing. Bulk RNA sequencing was performed on patients’ tumors as well.
Then, the researchers used a computational pipeline called OpenVax to identify candidate neoantigens. This pipeline, developed at Mount Sinai, identified and prioritized candidate neoantigens using predicted MHC class I binding affinity and neoantigen abundance.
OpenVax identified an average of 71.5 neoantigens per patient (range, 7-193). The goal was to synthesize a maximum of 10 peptides per patient, but two patients did not have an adequate number of neoantigens.
Vaccine administration
The peptides were administered over the course of 27 weeks along with poly-ICLC and a tetanus helper peptide. Before receiving their vaccine doses, patients with solid tumors had undergone curative-intent surgery, and those with multiple myeloma had undergone autologous stem cell transplant.
“Most experimental personalized cancer vaccines are administered in the metastatic setting, but prior research indicates that immunotherapies tend to be more effective in patients who have less cancer spread,” principal investigator Nina Bhardwaj, MD, PhD , of Mount Sinai, explained in a press release .
“We have, therefore, developed a neoantigen vaccine that is administered after standard-of-care adjuvant therapy, such as surgery in solid tumors and bone marrow transplant in multiple myeloma, when patients have minimal, typically microscopic, residual disease.”
Feasibility, safety, and immunogenicity
PGV-001 was synthesized for 15 patients and administered to 13 of them. Six of the 13 patients had head and neck squamous cell carcinoma, three had multiple myeloma, two had non–small cell lung cancer, one had breast cancer, and one had urothelial carcinoma.
Eleven patients received all 10 intended doses, and two patients received at least 8 doses.
“The vaccine was well tolerated, with only half of patients experiencing mild, grade 1 adverse events,” Dr. Marron said.
Transient injection site reactions occurred in four patients, and grade 1 fever was reported in one patient.
Immune monitoring is ongoing, but an initial analysis in one patient showed “robust responses” in CD4 and CD8 T cells by intracellular cytokine staining for interferon-gamma, tumor necrosis factor–alpha, and interleukin-2 after in vitro expansion in the presence of vaccine antigens, according to the researchers.
Dr. Marron noted that robust T-cell reactivity was seen at the completion of all 10 doses but was not seen after the 6th dose, and this supports the need for a prolonged dosing schedule.
Survival and subsequent therapy
At a mean follow-up of 880 days, four patients had no evidence of disease and had not received subsequent therapy. This includes one patient with stage IIIA non–small cell lung cancer, one with stage IVA HER-2 positive breast cancer, one with stage II urothelial carcinoma, and one with multiple myeloma.
Four patients were alive and receiving subsequent lines of therapy. Two of these patients had significant responses to anti–PD-1 therapy.
Three patients have died, two of whom had documented recurrence of their malignancy. The last two patients were lost to follow-up without documented recurrence.
“Our results demonstrate that the OpenVax pipeline is a viable approach to generate a safe, personalized cancer vaccine, which could potentially be used to treat a range of tumor types,” Dr. Bhardwaj said.
Trials combining neoantigens identified with the OpenVax platform are ongoing in patients with urothelial carcinoma and glioblastoma multiforme, Dr. Marron said.
The current study ( NCT02721043 ) is sponsored by Dr. Bhardwaj. Dr. Marron and Dr. Bhardwaj reported having no disclosures. Their colleagues disclosed relationships with Bristol Myers Squibb, Sema4, and Related Sciences.
FROM AACR 2021
Low-calorie diet linked to improved chemo response in leukemia
Children and adolescents with leukemia who were placed on a restrictive diet and exercise regimen concurrent with starting chemotherapy showed responses to treatment that were better than those historically seen in such patients.
This apparently improved response suggests it is possible to boost treatment efficacy without raising the dose – or toxicity – of chemotherapy.
“To our knowledge, this is the first study in any hematologic malignancy to demonstrate potential benefit from caloric restriction via diet and exercise to augment chemotherapy efficacy and improve disease response, the authors reported.
The findings come from the IDEAL pilot trial, conducted in 40 young patients (mean age, 15 years; range, 10-21 years) diagnosed with high-risk B-cell acute lymphoblastic leukemia (B-ALL).
The study was published online April 1 in Blood Advances.
The diet and exercise regimen is a departure from current recommendations for patients with leukemia.
“This was a major paradigm shift – until now, many oncologists encouraged ‘comfort foods’ and increased calories to get through the rigor of chemotherapy,” first author Etan Orgel, MD, of Children’s Hospital Los Angeles and the University of Southern California, also in Los Angeles.
The results from this pilot trial suggest that “the era of encouraging comfort food should be in the past; over-nutrition is likely harmful, and diet and exercise are important tools to harness during chemotherapy,” he said.
Dr. Orgel added that childhood ALL was selected because it is the most common cancer of childhood, but the findings could have potential relevance in other cancer types in children as well as adults.
Commenting on the study, Patrick Brown, MD, director of the pediatric leukemia program at Johns Hopkins University, Baltimore, said the findings are important, albeit preliminary.
“I think the most important contribution of this pilot study is to show that it is possible to change the nutrition and exercise habits of children and adolescents during the initial month of treatment for ALL,” he said in an interview.
“We have to be cautious about the preliminary finding that these changes resulted in deeper remissions – this will need to be confirmed in a larger study,” added Dr. Brown, who was not involved with the research.
Dr. Orgel noted that a prospective, randomized trial, IDEAL-2, is launching later this year to further evaluate the intervention.
Obesity linked to poorer chemotherapy response
Among children and adolescents who start treatment for B-ALL, as many as 40% are overweight or obese, noted the study authors.
Those who are obese have more than a twofold greater risk of having persistent minimal residual disease (MRD) at the end of chemotherapy, considered the strongest patient-level predictor of poor outcome and a common guide for therapy intensification.
The problem is compounded by weight gain that is common during treatment as a result of prolonged chemotherapy and sedentary behavior, they commented.
With studies of obese mice linking calorie and fat restriction to improved survival after chemotherapy, the authors theorized that a calorie- and fat-restrictive diet and exercise could help improve outcomes after chemotherapy in humans.
Participants were enrolled at Children’s Hospital Los Angeles and City of Hope National Medical Center in nearby Duarte. After they were started on chemotherapy, they were placed on a low-carb, low-fat, and low-sugar diet tailored to patient needs and preferences, as well as a moderate daily exercise regimen, and continued on this regimen throughout the 4-week induction phase.
Following the intervention, there were no significant reductions observed in median gain of fat mass at the end of the intervention, compared with baseline (P = .13). However, in the subgroup of patients who were overweight or obese at baseline, the reduction in fat mass was indeed significant versus baseline (+1.5% vs. +9.7% at baseline; P = .02).
Importantly, after adjustment for prognostic factors, adherence to the intervention was associated with a significant reduction in the risk of MRD, compared with recent historical controls who received the same induction therapy at the same institution, but no intervention (odds ratio, 0.30; P = .02).
The intervention was also associated with a lower detectable MRD, compared with the historical controls (OR, 0.16; one-sided P = .002).
“Most importantly, the IDEAL intervention reduced risk of MRD at the end of induction in all patients, irrespective of starting [body mass index] and after accounting for prognostic features,” the authors noted.
Adherence to diet high, exercise low
As many as 82% of study participants achieved the goal of 20% or more caloric deficit throughout the chemotherapy.
“Adherence to the diet was excellent, with caloric deficits and macronutrient goals achieved in nearly all patients, including in the lean group,” the authors reported.
Dr. Orgel added that families embraced the chance to play an active role in the cancer therapy. “In our view, they couldn’t control their disease or their chemotherapy, but this, they could,” he said.
Conversely, adherence to the prescribed exercise was low – just 31.2%, with the inactivity during the first month likely contributed to the similar loss of muscle mass that occurred in both cohorts, Dr. Orgel noted.
“The [low exercise adherence] unfortunately was not a surprise, as it is often difficult to exercise and be active during chemotherapy,” he said.
Key aspects of physical activity will be refined in further studies, Dr. Orgel added.
Insulin sensitivity, adiponectin key factors?
Patients receiving the intervention showed improved insulin sensitivity and reductions in circulating insulin, which are notable in that insulin has been linked to mechanisms that counter chemoresistance, the authors noted.
Furthermore, the decreases in insulin were accompanied by notable elevations in circulating adiponectin, a protein hormone produced and secreted by fat cells.
“Adiponectin was certainly a surprise, as until now it did not appear to play a major role in cancer cell resistance to chemotherapy,” Dr. Orgel said.
“It is too soon to say they are central to the mechanism of the intervention, but the large differences in adiponectin and insulin sensitivity found in children in the trial have definitely highlighted these as important for future study,” he added.
Dr. Orgel, the study coauthors, and Dr. Brown disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Children and adolescents with leukemia who were placed on a restrictive diet and exercise regimen concurrent with starting chemotherapy showed responses to treatment that were better than those historically seen in such patients.
This apparently improved response suggests it is possible to boost treatment efficacy without raising the dose – or toxicity – of chemotherapy.
“To our knowledge, this is the first study in any hematologic malignancy to demonstrate potential benefit from caloric restriction via diet and exercise to augment chemotherapy efficacy and improve disease response, the authors reported.
The findings come from the IDEAL pilot trial, conducted in 40 young patients (mean age, 15 years; range, 10-21 years) diagnosed with high-risk B-cell acute lymphoblastic leukemia (B-ALL).
The study was published online April 1 in Blood Advances.
The diet and exercise regimen is a departure from current recommendations for patients with leukemia.
“This was a major paradigm shift – until now, many oncologists encouraged ‘comfort foods’ and increased calories to get through the rigor of chemotherapy,” first author Etan Orgel, MD, of Children’s Hospital Los Angeles and the University of Southern California, also in Los Angeles.
The results from this pilot trial suggest that “the era of encouraging comfort food should be in the past; over-nutrition is likely harmful, and diet and exercise are important tools to harness during chemotherapy,” he said.
Dr. Orgel added that childhood ALL was selected because it is the most common cancer of childhood, but the findings could have potential relevance in other cancer types in children as well as adults.
Commenting on the study, Patrick Brown, MD, director of the pediatric leukemia program at Johns Hopkins University, Baltimore, said the findings are important, albeit preliminary.
“I think the most important contribution of this pilot study is to show that it is possible to change the nutrition and exercise habits of children and adolescents during the initial month of treatment for ALL,” he said in an interview.
“We have to be cautious about the preliminary finding that these changes resulted in deeper remissions – this will need to be confirmed in a larger study,” added Dr. Brown, who was not involved with the research.
Dr. Orgel noted that a prospective, randomized trial, IDEAL-2, is launching later this year to further evaluate the intervention.
Obesity linked to poorer chemotherapy response
Among children and adolescents who start treatment for B-ALL, as many as 40% are overweight or obese, noted the study authors.
Those who are obese have more than a twofold greater risk of having persistent minimal residual disease (MRD) at the end of chemotherapy, considered the strongest patient-level predictor of poor outcome and a common guide for therapy intensification.
The problem is compounded by weight gain that is common during treatment as a result of prolonged chemotherapy and sedentary behavior, they commented.
With studies of obese mice linking calorie and fat restriction to improved survival after chemotherapy, the authors theorized that a calorie- and fat-restrictive diet and exercise could help improve outcomes after chemotherapy in humans.
Participants were enrolled at Children’s Hospital Los Angeles and City of Hope National Medical Center in nearby Duarte. After they were started on chemotherapy, they were placed on a low-carb, low-fat, and low-sugar diet tailored to patient needs and preferences, as well as a moderate daily exercise regimen, and continued on this regimen throughout the 4-week induction phase.
Following the intervention, there were no significant reductions observed in median gain of fat mass at the end of the intervention, compared with baseline (P = .13). However, in the subgroup of patients who were overweight or obese at baseline, the reduction in fat mass was indeed significant versus baseline (+1.5% vs. +9.7% at baseline; P = .02).
Importantly, after adjustment for prognostic factors, adherence to the intervention was associated with a significant reduction in the risk of MRD, compared with recent historical controls who received the same induction therapy at the same institution, but no intervention (odds ratio, 0.30; P = .02).
The intervention was also associated with a lower detectable MRD, compared with the historical controls (OR, 0.16; one-sided P = .002).
“Most importantly, the IDEAL intervention reduced risk of MRD at the end of induction in all patients, irrespective of starting [body mass index] and after accounting for prognostic features,” the authors noted.
Adherence to diet high, exercise low
As many as 82% of study participants achieved the goal of 20% or more caloric deficit throughout the chemotherapy.
“Adherence to the diet was excellent, with caloric deficits and macronutrient goals achieved in nearly all patients, including in the lean group,” the authors reported.
Dr. Orgel added that families embraced the chance to play an active role in the cancer therapy. “In our view, they couldn’t control their disease or their chemotherapy, but this, they could,” he said.
Conversely, adherence to the prescribed exercise was low – just 31.2%, with the inactivity during the first month likely contributed to the similar loss of muscle mass that occurred in both cohorts, Dr. Orgel noted.
“The [low exercise adherence] unfortunately was not a surprise, as it is often difficult to exercise and be active during chemotherapy,” he said.
Key aspects of physical activity will be refined in further studies, Dr. Orgel added.
Insulin sensitivity, adiponectin key factors?
Patients receiving the intervention showed improved insulin sensitivity and reductions in circulating insulin, which are notable in that insulin has been linked to mechanisms that counter chemoresistance, the authors noted.
Furthermore, the decreases in insulin were accompanied by notable elevations in circulating adiponectin, a protein hormone produced and secreted by fat cells.
“Adiponectin was certainly a surprise, as until now it did not appear to play a major role in cancer cell resistance to chemotherapy,” Dr. Orgel said.
“It is too soon to say they are central to the mechanism of the intervention, but the large differences in adiponectin and insulin sensitivity found in children in the trial have definitely highlighted these as important for future study,” he added.
Dr. Orgel, the study coauthors, and Dr. Brown disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Children and adolescents with leukemia who were placed on a restrictive diet and exercise regimen concurrent with starting chemotherapy showed responses to treatment that were better than those historically seen in such patients.
This apparently improved response suggests it is possible to boost treatment efficacy without raising the dose – or toxicity – of chemotherapy.
“To our knowledge, this is the first study in any hematologic malignancy to demonstrate potential benefit from caloric restriction via diet and exercise to augment chemotherapy efficacy and improve disease response, the authors reported.
The findings come from the IDEAL pilot trial, conducted in 40 young patients (mean age, 15 years; range, 10-21 years) diagnosed with high-risk B-cell acute lymphoblastic leukemia (B-ALL).
The study was published online April 1 in Blood Advances.
The diet and exercise regimen is a departure from current recommendations for patients with leukemia.
“This was a major paradigm shift – until now, many oncologists encouraged ‘comfort foods’ and increased calories to get through the rigor of chemotherapy,” first author Etan Orgel, MD, of Children’s Hospital Los Angeles and the University of Southern California, also in Los Angeles.
The results from this pilot trial suggest that “the era of encouraging comfort food should be in the past; over-nutrition is likely harmful, and diet and exercise are important tools to harness during chemotherapy,” he said.
Dr. Orgel added that childhood ALL was selected because it is the most common cancer of childhood, but the findings could have potential relevance in other cancer types in children as well as adults.
Commenting on the study, Patrick Brown, MD, director of the pediatric leukemia program at Johns Hopkins University, Baltimore, said the findings are important, albeit preliminary.
“I think the most important contribution of this pilot study is to show that it is possible to change the nutrition and exercise habits of children and adolescents during the initial month of treatment for ALL,” he said in an interview.
“We have to be cautious about the preliminary finding that these changes resulted in deeper remissions – this will need to be confirmed in a larger study,” added Dr. Brown, who was not involved with the research.
Dr. Orgel noted that a prospective, randomized trial, IDEAL-2, is launching later this year to further evaluate the intervention.
Obesity linked to poorer chemotherapy response
Among children and adolescents who start treatment for B-ALL, as many as 40% are overweight or obese, noted the study authors.
Those who are obese have more than a twofold greater risk of having persistent minimal residual disease (MRD) at the end of chemotherapy, considered the strongest patient-level predictor of poor outcome and a common guide for therapy intensification.
The problem is compounded by weight gain that is common during treatment as a result of prolonged chemotherapy and sedentary behavior, they commented.
With studies of obese mice linking calorie and fat restriction to improved survival after chemotherapy, the authors theorized that a calorie- and fat-restrictive diet and exercise could help improve outcomes after chemotherapy in humans.
Participants were enrolled at Children’s Hospital Los Angeles and City of Hope National Medical Center in nearby Duarte. After they were started on chemotherapy, they were placed on a low-carb, low-fat, and low-sugar diet tailored to patient needs and preferences, as well as a moderate daily exercise regimen, and continued on this regimen throughout the 4-week induction phase.
Following the intervention, there were no significant reductions observed in median gain of fat mass at the end of the intervention, compared with baseline (P = .13). However, in the subgroup of patients who were overweight or obese at baseline, the reduction in fat mass was indeed significant versus baseline (+1.5% vs. +9.7% at baseline; P = .02).
Importantly, after adjustment for prognostic factors, adherence to the intervention was associated with a significant reduction in the risk of MRD, compared with recent historical controls who received the same induction therapy at the same institution, but no intervention (odds ratio, 0.30; P = .02).
The intervention was also associated with a lower detectable MRD, compared with the historical controls (OR, 0.16; one-sided P = .002).
“Most importantly, the IDEAL intervention reduced risk of MRD at the end of induction in all patients, irrespective of starting [body mass index] and after accounting for prognostic features,” the authors noted.
Adherence to diet high, exercise low
As many as 82% of study participants achieved the goal of 20% or more caloric deficit throughout the chemotherapy.
“Adherence to the diet was excellent, with caloric deficits and macronutrient goals achieved in nearly all patients, including in the lean group,” the authors reported.
Dr. Orgel added that families embraced the chance to play an active role in the cancer therapy. “In our view, they couldn’t control their disease or their chemotherapy, but this, they could,” he said.
Conversely, adherence to the prescribed exercise was low – just 31.2%, with the inactivity during the first month likely contributed to the similar loss of muscle mass that occurred in both cohorts, Dr. Orgel noted.
“The [low exercise adherence] unfortunately was not a surprise, as it is often difficult to exercise and be active during chemotherapy,” he said.
Key aspects of physical activity will be refined in further studies, Dr. Orgel added.
Insulin sensitivity, adiponectin key factors?
Patients receiving the intervention showed improved insulin sensitivity and reductions in circulating insulin, which are notable in that insulin has been linked to mechanisms that counter chemoresistance, the authors noted.
Furthermore, the decreases in insulin were accompanied by notable elevations in circulating adiponectin, a protein hormone produced and secreted by fat cells.
“Adiponectin was certainly a surprise, as until now it did not appear to play a major role in cancer cell resistance to chemotherapy,” Dr. Orgel said.
“It is too soon to say they are central to the mechanism of the intervention, but the large differences in adiponectin and insulin sensitivity found in children in the trial have definitely highlighted these as important for future study,” he added.
Dr. Orgel, the study coauthors, and Dr. Brown disclosed no relevant financial relationships.
A version of this article first appeared on Medscape.com.
Evidence favors lower-dose R-CHOP for fit, very elderly DLBCL patients
A dose-adjusted R-CHOP may be the best treatment for elderly patients with diffuse large beta-cell lymphoma (DLBCL), according to a review of 38 studies that examined this aged population.
In addition, treatment choices based on new tools such as the Comprehensive Geriatric Assessment appeared to provide useful guidance based on the comorbidities and frailty index of this group of patients, according to Alda Tavares, MD, of Hospital Pedro Hispano, Matosinhos (Portugal) Local Health Unit, and Ilídia Moreira, MD, of the Portuguese Institute of Oncology of Porto.
Study characteristics
Of the 38 studies assessed, 13 were retrospective and 25 were phase II/III clinical trials. Most of these studies investigated the efficacy of dose-adjusted R-CHOP regimen, according to the review published online in Critical Reviews in Oncology/Hematology.
Alternative therapeutic drugs as well as the use of geriatric assessment were also investigated.
In terms of the elderly populations assessed, 11 out of 38 studies included at least 30 patients over age 80 years, although 11 other studies did not specify the number of patients older than 80 years. Eight of the studies included exclusively patients aged 80 years and over. Three of these studies were phase II trials.
Only six of the clinical trials required a geriatric assessment tool for inclusion criteria or therapeutic regime choice, using the Cumulative Illness Rating Scale–Geriatric (CIRS-G), the performance in activities of daily living (ADL) and/or instrumental activities of daily living (IADL) tools.
Most of the studies investigated the efficacy of R-CHOP regimen at different doses and variations, with 11 studies using alternative anthracycline in place of doxorubicin.
MiniCHOP mattered
Elderly patients over 80 years achieved complete response (CR) rates from 37.2% to 66.7% and 2-year overall survival (OS) from 31.9% to 64.7% across the studies reviewed. Overall, for fit patients aged 80 and over, the strongest evidence favored the use of an R-miniCHOP regimen, according to the authors.
In the 25 studies with treatment based on R-CHOP/modified R-CHOP or immunochemotherapy with an alternative anthracycline, the CR rate was below 50% in three studies and over 60% in the majority. Higher CR rates of 71%-88.9% were achieved in eight studies.
For patients over 80 years, the strongest evidence favored rituximab/ofatumumab-miniCHOP, based on two studies. In both studies, patients over 80 years old, without significant comorbidities, received CHOP regime with a dose reduction of about 50% (miniCHOP: cyclophosphamide 400 mg/m2, doxorubicin 25 mg/m2, and 1 mg vincristine on day 1 of each cycle, and prednisone 40 mg/m2 on days 1-5) plus an anti–CD-20 antibody (rituximab 375 mg/m2 or ofatumumab 1,000 mg). The first of these studies obtained CR rate of 62% and 2-year OS of 59% with low toxicities. The second study achieved slightly better results, according to the reviewers, who suggested the difference was possibly because of a prephase treatment and/or the use of ofatumumab.
One study group developed a simple prognostic model based on multivariate analysis of 108 patients aged 80 years and older treated in their study with R-CHOP at full (48%) or reduced dose (51%). Patients with at least two out of three risk factors (age > 85 years, revised International Prognostic Index score 3-5 and CIRS > 5) had worse survival than did those with 0-1 risk factors, with a median OS of 12 months vs. 45 months, P = .001, respectively).
“All these studies results favor the tailored treatment approach,” the reviewers stated. “More prospective studies are still needed to demonstrate and validate the adequate tools for the selection of patients and their optimal treatment. They would provide the grounds for clinical therapeutic decision, aiming for tailored treatment and fulfilling best individual expectations and outcome,” they concluded.
The authors reported that they received no research funds for the study and that they had no disclosures.
A dose-adjusted R-CHOP may be the best treatment for elderly patients with diffuse large beta-cell lymphoma (DLBCL), according to a review of 38 studies that examined this aged population.
In addition, treatment choices based on new tools such as the Comprehensive Geriatric Assessment appeared to provide useful guidance based on the comorbidities and frailty index of this group of patients, according to Alda Tavares, MD, of Hospital Pedro Hispano, Matosinhos (Portugal) Local Health Unit, and Ilídia Moreira, MD, of the Portuguese Institute of Oncology of Porto.
Study characteristics
Of the 38 studies assessed, 13 were retrospective and 25 were phase II/III clinical trials. Most of these studies investigated the efficacy of dose-adjusted R-CHOP regimen, according to the review published online in Critical Reviews in Oncology/Hematology.
Alternative therapeutic drugs as well as the use of geriatric assessment were also investigated.
In terms of the elderly populations assessed, 11 out of 38 studies included at least 30 patients over age 80 years, although 11 other studies did not specify the number of patients older than 80 years. Eight of the studies included exclusively patients aged 80 years and over. Three of these studies were phase II trials.
Only six of the clinical trials required a geriatric assessment tool for inclusion criteria or therapeutic regime choice, using the Cumulative Illness Rating Scale–Geriatric (CIRS-G), the performance in activities of daily living (ADL) and/or instrumental activities of daily living (IADL) tools.
Most of the studies investigated the efficacy of R-CHOP regimen at different doses and variations, with 11 studies using alternative anthracycline in place of doxorubicin.
MiniCHOP mattered
Elderly patients over 80 years achieved complete response (CR) rates from 37.2% to 66.7% and 2-year overall survival (OS) from 31.9% to 64.7% across the studies reviewed. Overall, for fit patients aged 80 and over, the strongest evidence favored the use of an R-miniCHOP regimen, according to the authors.
In the 25 studies with treatment based on R-CHOP/modified R-CHOP or immunochemotherapy with an alternative anthracycline, the CR rate was below 50% in three studies and over 60% in the majority. Higher CR rates of 71%-88.9% were achieved in eight studies.
For patients over 80 years, the strongest evidence favored rituximab/ofatumumab-miniCHOP, based on two studies. In both studies, patients over 80 years old, without significant comorbidities, received CHOP regime with a dose reduction of about 50% (miniCHOP: cyclophosphamide 400 mg/m2, doxorubicin 25 mg/m2, and 1 mg vincristine on day 1 of each cycle, and prednisone 40 mg/m2 on days 1-5) plus an anti–CD-20 antibody (rituximab 375 mg/m2 or ofatumumab 1,000 mg). The first of these studies obtained CR rate of 62% and 2-year OS of 59% with low toxicities. The second study achieved slightly better results, according to the reviewers, who suggested the difference was possibly because of a prephase treatment and/or the use of ofatumumab.
One study group developed a simple prognostic model based on multivariate analysis of 108 patients aged 80 years and older treated in their study with R-CHOP at full (48%) or reduced dose (51%). Patients with at least two out of three risk factors (age > 85 years, revised International Prognostic Index score 3-5 and CIRS > 5) had worse survival than did those with 0-1 risk factors, with a median OS of 12 months vs. 45 months, P = .001, respectively).
“All these studies results favor the tailored treatment approach,” the reviewers stated. “More prospective studies are still needed to demonstrate and validate the adequate tools for the selection of patients and their optimal treatment. They would provide the grounds for clinical therapeutic decision, aiming for tailored treatment and fulfilling best individual expectations and outcome,” they concluded.
The authors reported that they received no research funds for the study and that they had no disclosures.
A dose-adjusted R-CHOP may be the best treatment for elderly patients with diffuse large beta-cell lymphoma (DLBCL), according to a review of 38 studies that examined this aged population.
In addition, treatment choices based on new tools such as the Comprehensive Geriatric Assessment appeared to provide useful guidance based on the comorbidities and frailty index of this group of patients, according to Alda Tavares, MD, of Hospital Pedro Hispano, Matosinhos (Portugal) Local Health Unit, and Ilídia Moreira, MD, of the Portuguese Institute of Oncology of Porto.
Study characteristics
Of the 38 studies assessed, 13 were retrospective and 25 were phase II/III clinical trials. Most of these studies investigated the efficacy of dose-adjusted R-CHOP regimen, according to the review published online in Critical Reviews in Oncology/Hematology.
Alternative therapeutic drugs as well as the use of geriatric assessment were also investigated.
In terms of the elderly populations assessed, 11 out of 38 studies included at least 30 patients over age 80 years, although 11 other studies did not specify the number of patients older than 80 years. Eight of the studies included exclusively patients aged 80 years and over. Three of these studies were phase II trials.
Only six of the clinical trials required a geriatric assessment tool for inclusion criteria or therapeutic regime choice, using the Cumulative Illness Rating Scale–Geriatric (CIRS-G), the performance in activities of daily living (ADL) and/or instrumental activities of daily living (IADL) tools.
Most of the studies investigated the efficacy of R-CHOP regimen at different doses and variations, with 11 studies using alternative anthracycline in place of doxorubicin.
MiniCHOP mattered
Elderly patients over 80 years achieved complete response (CR) rates from 37.2% to 66.7% and 2-year overall survival (OS) from 31.9% to 64.7% across the studies reviewed. Overall, for fit patients aged 80 and over, the strongest evidence favored the use of an R-miniCHOP regimen, according to the authors.
In the 25 studies with treatment based on R-CHOP/modified R-CHOP or immunochemotherapy with an alternative anthracycline, the CR rate was below 50% in three studies and over 60% in the majority. Higher CR rates of 71%-88.9% were achieved in eight studies.
For patients over 80 years, the strongest evidence favored rituximab/ofatumumab-miniCHOP, based on two studies. In both studies, patients over 80 years old, without significant comorbidities, received CHOP regime with a dose reduction of about 50% (miniCHOP: cyclophosphamide 400 mg/m2, doxorubicin 25 mg/m2, and 1 mg vincristine on day 1 of each cycle, and prednisone 40 mg/m2 on days 1-5) plus an anti–CD-20 antibody (rituximab 375 mg/m2 or ofatumumab 1,000 mg). The first of these studies obtained CR rate of 62% and 2-year OS of 59% with low toxicities. The second study achieved slightly better results, according to the reviewers, who suggested the difference was possibly because of a prephase treatment and/or the use of ofatumumab.
One study group developed a simple prognostic model based on multivariate analysis of 108 patients aged 80 years and older treated in their study with R-CHOP at full (48%) or reduced dose (51%). Patients with at least two out of three risk factors (age > 85 years, revised International Prognostic Index score 3-5 and CIRS > 5) had worse survival than did those with 0-1 risk factors, with a median OS of 12 months vs. 45 months, P = .001, respectively).
“All these studies results favor the tailored treatment approach,” the reviewers stated. “More prospective studies are still needed to demonstrate and validate the adequate tools for the selection of patients and their optimal treatment. They would provide the grounds for clinical therapeutic decision, aiming for tailored treatment and fulfilling best individual expectations and outcome,” they concluded.
The authors reported that they received no research funds for the study and that they had no disclosures.
FROM CRITICAL REVIEWS IN ONCOLOGY/HEMATOLOGY
Next winter may be rough: Models predict ‘considerable surge’ of COVID
It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.
Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.
“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.
But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.
With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.
Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
Decreased infections
If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.
The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”
B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.
In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.
Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.
The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
Human factors
Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.
By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.
In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.
Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.
However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
Double surge
Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.
He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.
Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.
Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.
In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.
Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.
A version of this article first appeared on Medscape.com.
It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.
Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.
“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.
But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.
With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.
Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
Decreased infections
If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.
The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”
B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.
In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.
Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.
The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
Human factors
Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.
By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.
In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.
Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.
However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
Double surge
Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.
He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.
Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.
Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.
In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.
Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.
A version of this article first appeared on Medscape.com.
It’s likely the United States will see another surge of COVID-19 this winter, warned Christopher Murray, MD, director of the Institute for Health Metrics and Evaluation (IHME) at the University of Washington in Seattle.
Speaking at the national conference of State of Reform on April 8, Dr. Murray cited the seasonality of the SARS-CoV-2 virus, which wanes in the summer and waxes in the winter. The “optimistic forecast” of IHME, which has modeled the course of the pandemic for the past 13 months, is that daily deaths will rise a bit in the next month, then decline from May through August, he said.
“Summer should be fairly quiet in terms of COVID, if vaccinations rise and people don’t stop wearing masks,” Dr. Murray said.
But he added that “a considerable surge will occur over next winter,” because the new variants are more transmissible, and people will likely relax social distancing and mask wearing. The IHME predicts that the percentage of Americans who usually don masks will decline from 73% today to 21% by Aug. 1.
With a rapid decline in mask use and a rise in mobility, there will still be more than 1,000 deaths each day by July 1, Dr. Murray said. In a forecast released the day after Dr. Murray spoke, the IHME predicted that by Aug. 1, there will be a total of 618,523 U.S. deaths from COVID-19. Deaths could be as high as 696,651 if mobility among the vaccinated returns to prepandemic levels, the institute forecasts.
Based on cell phone data, Dr. Murray said, the amount of mobility in the United States has already risen to the level of March 2020, when the pandemic was just getting underway.
Decreased infections
If there’s one piece of good news in the latest IHME report, it’s that the estimated number of people infected (including those not tested) will drop from 111,581 today to a projected 17,502 on Aug. 1. But in a worst-case scenario, with sharply higher mobility among vaccinated people, the case count on that date would only fall to 73,842.
The SARS-CoV-2 variants are another factor of concern. Dr. Murray distinguished between variants like the one first identified in the U.K. (B.1.1.7) and other “escape variants.”
B.1.1.7, which is now the dominant strain in the United States, increases transmission but doesn’t necessarily escape the immune system or vaccines, he explained.
In contrast, if someone is infected with a variant such as the South African or the Brazilian mutations, he said, a previous COVID-19 infection might not protect the person, and vaccines are less effective against those variants.
Cross-variant immunity may range from 0% to 60% for escape variants, based on the slim amount of data now available, Dr. Murray said. In his view, these variants will be the long-term driver of the pandemic in the United States, while the United Kingdom variant is the short-term driver.
The latest data, he said, show that the Pfizer/BioNTech and Moderna vaccines are 75% effective against the escape variants, with lower efficacy for other vaccines. But booster shots may still be required to protect people against some variants.
Human factors
Human behavior will also help determine the course of the pandemic, he noted. Vaccine hesitancy, for example, is still high in the United States.
By the end of May, he predicted, about 180 million people will have received about two doses of vaccine. After that, he said, “vaccination will flatline due to lack of demand.” The two unknowns are how much campaigns to promote vaccination will increase vaccine confidence, and when children will be vaccinated.
In the United States, he said, 69% of adults have been vaccinated or want to get a shot. But that percentage has dropped 5 points since February, and vaccine confidence varies by state.
Dr. Murray emphasized that the winter surge he predicts can be blocked if people change their behaviors. These include a rise in vaccine confidence to 80% and continued mask wearing by most people.
However, if vaccine confidence and mask wearing decline, state governments continue to drop social distancing rules, and the uptake of boosters is low, the winter surge could be more serious, he said.
Double surge
Murray also raised the possibility of a double surge of COVID-19 and influenza this winter. Widely expected last winter, this double surge never materialized here or elsewhere, partly because of mask wearing. But Dr. Murray said it could happen this year: History shows that the flu tends to be stronger in years after weak outbreaks.
He advised hospitals to prepare now for whatever might come later this year. Public health authorities, he said, should speed up vaccination, monitor variants closely with additional sequencing, and try to modify behavior in high-risk groups.
Asked to explain the recent surge of COVID-19 cases in Michigan, Dr. Murray attributed it partly to the spread of the B.1.1.7 (U.K.) variant. But he noted that the U.K. variant has expanded even more widely in some other states that haven’t had an explosive surge like Michigan’s.
Moreover, he noted, Michigan doesn’t have low mask use or high mobility. So the upward spiral of COVID-19 infections there is very concerning, he said.
In regard to the role of children as reservoirs of the virus, Dr. Murray pointed out that views on this have changed around the world. For a while, people thought kids didn’t spread COVID-19 very much. That view shifted when U.K. data showed that child transmission of the B.1.1.7 variant increased by half to 9% of contacts in comparison with the original virus strain.
Dutch data, similarly, showed schools contributing to the latest outbreaks, and some European nations have closed schools. In the United States, the trend is to open them.
A version of this article first appeared on Medscape.com.
FDA, CDC urge pause of J&J COVID vaccine
The Food and Drug Administration and Centers for Disease Control and Prevention on April 13 recommended that use of the Johnson & Johnson COVID-19 vaccine be paused after reports of blood clots in patients receiving the shot, the agencies have announced.
In a statement, FDA said 6.8 million doses of the J&J vaccine have been administered and the agency is investigating six reported cases of a rare and severe blood clot occurring in patients who received the vaccine.
The pause is intended to give time to alert the public to this "very rare" condition, experts said during a joint CDC-FDA media briefing April 13.
"It was clear to us that we needed to alert the public," Janet Woodcock, MD, acting FDA commissioner, said. The move also will allow "time for the healthcare community to learn what they need to know about how to diagnose, treat and report" any additional cases.
The CDC will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the cases.
"I know the information today will be very concerning to Americans who have already received the Johnson & Johnson vaccine," said Anne Schuchat, MD, principal deputy director at the CDC.
"For people who got the vaccine more than one month ago, the risk is very low at this time," she added. "For people who recently got the vaccine, in the last couple of weeks, look for symptoms."
Headache, leg pain, abdominal pain, and shortness of breath were among the reported symptoms. All six cases arose within 6 to 13 days of receipt of the Johnson & Johnson vaccine.
Traditional treatment dangerous
Importantly, treatment for traditional blood clots, such as the drug heparin, should not be used for these clots. "The issue here with these types of blood clots is that if one administers the standard treatment we give for blood clots, one can cause tremendous harm or it can be fatal," said Peter Marks, MD, director of the FDA Center for Biologics Evaluation and Research.
If health care providers see people with these symptoms along with a low platelet count or blood clots, they should ask about any recent vaccinations, Dr. Marks added.
Headache is a common side effect of COVID-19 vaccination, Dr. Marks said, but it typically happens within a day or two. In contrast, the headaches associated with these blood clots come 1 to 2 weeks later and were very severe.
Not all of the six women involved in the events had a pre-existing condition or risk factor, Dr. Schuchat said.
Severe but 'extremely rare'
To put the numbers in context, the six reported events occurred among millions of people who received the Johnson & Johnson vaccine to date.
"There have been six reports of a severe stroke-like illness due to low platelet count and more than six million doses of the Johnson & Johnson vaccine have been administered so far," Dr. Schuchat said.
"I would like to stress these events are extremely rare," Dr. Woodcock said, "but we take all reports of adverse events after vaccination very seriously."
The company response
Johnson & Johnson in a statement said, "We are aware of an extremely rare disorder involving people with blood clots in combination with low platelets in a small number of individuals who have received our COVID-19 vaccine. The United States Centers for Disease Control (CDC) and Food and Drug Administration (FDA) are reviewing data involving six reported U.S. cases out of more than 6.8 million doses administered. Out of an abundance of caution, the CDC and FDA have recommended a pause in the use of our vaccine."
The company said they are also reviewing these cases with European regulators and "we have made the decision to proactively delay the rollout of our vaccine in Europe."
Overall vaccinations continuing apace
"This announcement will not have a significant impact on our vaccination plan. Johnson & Johnson vaccine makes up less than 5% of the recorded shots in arms in the United States to date," Jeff Zients, White House COVID-19 Response Coordinator, said in a statement.
"Based on actions taken by the president earlier this year, the United States has secured enough Pfizer and Moderna doses for 300 million Americans. We are working now with our state and federal partners to get anyone scheduled for a J&J vaccine quickly rescheduled for a Pfizer or Moderna vaccine," he added.
The likely duration of the pause remains unclear.
"I know this has been a long and difficult pandemic, and people are tired of the steps they have to take," Dr. Schuchat said. "Steps taken today make sure the health care system is ready to diagnose, treat and report [any additional cases] and the public has the information necessary to stay safe."
A version of this article first appeared on WebMD.com.
This article was updated 4/13/21.
The Food and Drug Administration and Centers for Disease Control and Prevention on April 13 recommended that use of the Johnson & Johnson COVID-19 vaccine be paused after reports of blood clots in patients receiving the shot, the agencies have announced.
In a statement, FDA said 6.8 million doses of the J&J vaccine have been administered and the agency is investigating six reported cases of a rare and severe blood clot occurring in patients who received the vaccine.
The pause is intended to give time to alert the public to this "very rare" condition, experts said during a joint CDC-FDA media briefing April 13.
"It was clear to us that we needed to alert the public," Janet Woodcock, MD, acting FDA commissioner, said. The move also will allow "time for the healthcare community to learn what they need to know about how to diagnose, treat and report" any additional cases.
The CDC will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the cases.
"I know the information today will be very concerning to Americans who have already received the Johnson & Johnson vaccine," said Anne Schuchat, MD, principal deputy director at the CDC.
"For people who got the vaccine more than one month ago, the risk is very low at this time," she added. "For people who recently got the vaccine, in the last couple of weeks, look for symptoms."
Headache, leg pain, abdominal pain, and shortness of breath were among the reported symptoms. All six cases arose within 6 to 13 days of receipt of the Johnson & Johnson vaccine.
Traditional treatment dangerous
Importantly, treatment for traditional blood clots, such as the drug heparin, should not be used for these clots. "The issue here with these types of blood clots is that if one administers the standard treatment we give for blood clots, one can cause tremendous harm or it can be fatal," said Peter Marks, MD, director of the FDA Center for Biologics Evaluation and Research.
If health care providers see people with these symptoms along with a low platelet count or blood clots, they should ask about any recent vaccinations, Dr. Marks added.
Headache is a common side effect of COVID-19 vaccination, Dr. Marks said, but it typically happens within a day or two. In contrast, the headaches associated with these blood clots come 1 to 2 weeks later and were very severe.
Not all of the six women involved in the events had a pre-existing condition or risk factor, Dr. Schuchat said.
Severe but 'extremely rare'
To put the numbers in context, the six reported events occurred among millions of people who received the Johnson & Johnson vaccine to date.
"There have been six reports of a severe stroke-like illness due to low platelet count and more than six million doses of the Johnson & Johnson vaccine have been administered so far," Dr. Schuchat said.
"I would like to stress these events are extremely rare," Dr. Woodcock said, "but we take all reports of adverse events after vaccination very seriously."
The company response
Johnson & Johnson in a statement said, "We are aware of an extremely rare disorder involving people with blood clots in combination with low platelets in a small number of individuals who have received our COVID-19 vaccine. The United States Centers for Disease Control (CDC) and Food and Drug Administration (FDA) are reviewing data involving six reported U.S. cases out of more than 6.8 million doses administered. Out of an abundance of caution, the CDC and FDA have recommended a pause in the use of our vaccine."
The company said they are also reviewing these cases with European regulators and "we have made the decision to proactively delay the rollout of our vaccine in Europe."
Overall vaccinations continuing apace
"This announcement will not have a significant impact on our vaccination plan. Johnson & Johnson vaccine makes up less than 5% of the recorded shots in arms in the United States to date," Jeff Zients, White House COVID-19 Response Coordinator, said in a statement.
"Based on actions taken by the president earlier this year, the United States has secured enough Pfizer and Moderna doses for 300 million Americans. We are working now with our state and federal partners to get anyone scheduled for a J&J vaccine quickly rescheduled for a Pfizer or Moderna vaccine," he added.
The likely duration of the pause remains unclear.
"I know this has been a long and difficult pandemic, and people are tired of the steps they have to take," Dr. Schuchat said. "Steps taken today make sure the health care system is ready to diagnose, treat and report [any additional cases] and the public has the information necessary to stay safe."
A version of this article first appeared on WebMD.com.
This article was updated 4/13/21.
The Food and Drug Administration and Centers for Disease Control and Prevention on April 13 recommended that use of the Johnson & Johnson COVID-19 vaccine be paused after reports of blood clots in patients receiving the shot, the agencies have announced.
In a statement, FDA said 6.8 million doses of the J&J vaccine have been administered and the agency is investigating six reported cases of a rare and severe blood clot occurring in patients who received the vaccine.
The pause is intended to give time to alert the public to this "very rare" condition, experts said during a joint CDC-FDA media briefing April 13.
"It was clear to us that we needed to alert the public," Janet Woodcock, MD, acting FDA commissioner, said. The move also will allow "time for the healthcare community to learn what they need to know about how to diagnose, treat and report" any additional cases.
The CDC will convene a meeting of the Advisory Committee on Immunization Practices on April 14 to review the cases.
"I know the information today will be very concerning to Americans who have already received the Johnson & Johnson vaccine," said Anne Schuchat, MD, principal deputy director at the CDC.
"For people who got the vaccine more than one month ago, the risk is very low at this time," she added. "For people who recently got the vaccine, in the last couple of weeks, look for symptoms."
Headache, leg pain, abdominal pain, and shortness of breath were among the reported symptoms. All six cases arose within 6 to 13 days of receipt of the Johnson & Johnson vaccine.
Traditional treatment dangerous
Importantly, treatment for traditional blood clots, such as the drug heparin, should not be used for these clots. "The issue here with these types of blood clots is that if one administers the standard treatment we give for blood clots, one can cause tremendous harm or it can be fatal," said Peter Marks, MD, director of the FDA Center for Biologics Evaluation and Research.
If health care providers see people with these symptoms along with a low platelet count or blood clots, they should ask about any recent vaccinations, Dr. Marks added.
Headache is a common side effect of COVID-19 vaccination, Dr. Marks said, but it typically happens within a day or two. In contrast, the headaches associated with these blood clots come 1 to 2 weeks later and were very severe.
Not all of the six women involved in the events had a pre-existing condition or risk factor, Dr. Schuchat said.
Severe but 'extremely rare'
To put the numbers in context, the six reported events occurred among millions of people who received the Johnson & Johnson vaccine to date.
"There have been six reports of a severe stroke-like illness due to low platelet count and more than six million doses of the Johnson & Johnson vaccine have been administered so far," Dr. Schuchat said.
"I would like to stress these events are extremely rare," Dr. Woodcock said, "but we take all reports of adverse events after vaccination very seriously."
The company response
Johnson & Johnson in a statement said, "We are aware of an extremely rare disorder involving people with blood clots in combination with low platelets in a small number of individuals who have received our COVID-19 vaccine. The United States Centers for Disease Control (CDC) and Food and Drug Administration (FDA) are reviewing data involving six reported U.S. cases out of more than 6.8 million doses administered. Out of an abundance of caution, the CDC and FDA have recommended a pause in the use of our vaccine."
The company said they are also reviewing these cases with European regulators and "we have made the decision to proactively delay the rollout of our vaccine in Europe."
Overall vaccinations continuing apace
"This announcement will not have a significant impact on our vaccination plan. Johnson & Johnson vaccine makes up less than 5% of the recorded shots in arms in the United States to date," Jeff Zients, White House COVID-19 Response Coordinator, said in a statement.
"Based on actions taken by the president earlier this year, the United States has secured enough Pfizer and Moderna doses for 300 million Americans. We are working now with our state and federal partners to get anyone scheduled for a J&J vaccine quickly rescheduled for a Pfizer or Moderna vaccine," he added.
The likely duration of the pause remains unclear.
"I know this has been a long and difficult pandemic, and people are tired of the steps they have to take," Dr. Schuchat said. "Steps taken today make sure the health care system is ready to diagnose, treat and report [any additional cases] and the public has the information necessary to stay safe."
A version of this article first appeared on WebMD.com.
This article was updated 4/13/21.
