Hematology News

Axicabtagene ciloleucel (axi-cel) can be safely administered and has substantial clinical benefit as part of first-line therapy in patients with high-risk large B-cell lymphoma, according to an investigator in a phase 2 study.

The chimeric antigen receptor (CAR) T-cell therapy had a “very high” overall response rate (ORR) of 85% and a complete response (CR) rate of 74% in the ZUMA-12 study, said investigator Sattva S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center in Houston.

Nearly three-quarters of responses were ongoing with a median of follow-up of about 9 months, Dr. Neelapu said in interim analysis of ZUMA-12 presented at the annual meeting of the American Society of Hematology, which was held virtually.

While axi-cel is approved for treatment of certain relapsed/refractory large B-cell lymphomas (LBCLs), Dr. Neelapu said this is the first-ever study evaluating a CAR T-cell therapy as a first-line treatment for patients with LBCL that is high risk as defined by histology or International Prognostic Index (IPI) scoring.

Treatment with axi-cel was guided by dynamic risk assessment, Dr. Neelapu explained, meaning that patients received the CAR T-cell treatment if they had a positive interim positron emission tomography (PET) scan after two cycles of an anti-CD20 monoclonal antibody and anthracycline-containing regimen.
 

Longer follow-up needed

The interim efficacy analysis is based on 27 evaluable patients out of 40 patients planned to be enrolled, meaning that the final analysis is needed, and longer follow-up is needed to ensure that durability is maintained, Dr. Neelapu said in a question-and-answer session following his presentation.

Nevertheless, the 74% complete response rate in the frontline setting is “quite encouraging” compared to historical data in high-risk LBCL, where CR rates have generally been less than 50%, Dr. Neelapu added.

“Assuming that long-term data in the final analysis confirms this encouraging activity, I think we likely would need a randomized phase 3 trial to compare (axi-cel) head-to-head with frontline therapy,” he said.

Without mature data available, it’s hard to say in this single-arm study how much axi-cel is improving outcomes at the cost of significant toxicity, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

Adverse events as reported by Dr. Neelapu included grade 3 cytokine release syndrome (CRS) in 9% of patients, and 25% grade 3 or greater neurologic events in 25%.

“It appears as though it may be salvaging some patients, as the response rate is higher than that expected for chemotherapy alone in this setting,” Dr. Diefenbach said in an interview, “but toxicity is not trivial, so the long-term data will provide better clarity as to the degree of benefit.”
 

Ongoing responses at 9 months

The phase 2 ZUMA-12 study includes patients classified as high risk based on MYC and BCL2 and/or BCL6 translocations, or by an International Prognostic Indicator score of 3 or greater.

Patients initially received two cycles of anti-CD20 monoclonal antibody therapy plus an anthracycline containing regimen. Those with a positive interim PET (score of 4 or 5 on the 5-point Deauville scale) received fludarabine/cyclophosphamide conditioning plus axi-cel as a single intravenous infusion of 2 x 106 CAR T cells per kg of body weight.

As of the report at the ASH meeting, 32 patient had received axi-cel, of whom 32 were evaluable for safety and 27 were evaluable for efficacy.

The ORR was 85% (23 of 27 patients), and the CR rate was 74% (20 of 27 patients), Dr. Neelapu reported, noting that with a median follow-up of 9.3 months, 70% of responders (19 of 27) were in ongoing response.

Median duration of response, progression-free survival, and overall survival have not been reached, he added.

Encephalopathy was the most common grade 3 or greater adverse event related to axi-cel, occurring in 16% of patients, while increased alanine aminotransferase and decreased neutrophil count were each seen in 9% of patients, Dr. Neelapu said.

All 32 patients experienced CRS, including grade 3 CRS in 3 patients (9%), according to the reported data. Neurologic events were seen in 22 patients (69%) including grade 3 or greater in 8 (25%). There were 2 grade 4 neurologic events – both encephalopathies that resolved, according to Dr. Neelapu – and no grade 5 neurologic events.

ZUMA-12 is sponsored by Kite, a Gilead Company. Dr. Neelapu reported disclosures related to Acerta, Adicet Bio, Bristol-Myers Squibb, Kite, and various other pharmaceutical and biotechnology companies.
 

SOURCE: Neelapu SS et al. ASH 2020, Abstract 405.

Axicabtagene ciloleucel (axi-cel) can be safely administered and has substantial clinical benefit as part of first-line therapy in patients with high-risk large B-cell lymphoma, according to an investigator in a phase 2 study.

The chimeric antigen receptor (CAR) T-cell therapy had a “very high” overall response rate (ORR) of 85% and a complete response (CR) rate of 74% in the ZUMA-12 study, said investigator Sattva S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center in Houston.

Nearly three-quarters of responses were ongoing with a median of follow-up of about 9 months, Dr. Neelapu said in interim analysis of ZUMA-12 presented at the annual meeting of the American Society of Hematology, which was held virtually.

While axi-cel is approved for treatment of certain relapsed/refractory large B-cell lymphomas (LBCLs), Dr. Neelapu said this is the first-ever study evaluating a CAR T-cell therapy as a first-line treatment for patients with LBCL that is high risk as defined by histology or International Prognostic Index (IPI) scoring.

Treatment with axi-cel was guided by dynamic risk assessment, Dr. Neelapu explained, meaning that patients received the CAR T-cell treatment if they had a positive interim positron emission tomography (PET) scan after two cycles of an anti-CD20 monoclonal antibody and anthracycline-containing regimen.
 

Longer follow-up needed

The interim efficacy analysis is based on 27 evaluable patients out of 40 patients planned to be enrolled, meaning that the final analysis is needed, and longer follow-up is needed to ensure that durability is maintained, Dr. Neelapu said in a question-and-answer session following his presentation.

Nevertheless, the 74% complete response rate in the frontline setting is “quite encouraging” compared to historical data in high-risk LBCL, where CR rates have generally been less than 50%, Dr. Neelapu added.

“Assuming that long-term data in the final analysis confirms this encouraging activity, I think we likely would need a randomized phase 3 trial to compare (axi-cel) head-to-head with frontline therapy,” he said.

Without mature data available, it’s hard to say in this single-arm study how much axi-cel is improving outcomes at the cost of significant toxicity, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

Adverse events as reported by Dr. Neelapu included grade 3 cytokine release syndrome (CRS) in 9% of patients, and 25% grade 3 or greater neurologic events in 25%.

“It appears as though it may be salvaging some patients, as the response rate is higher than that expected for chemotherapy alone in this setting,” Dr. Diefenbach said in an interview, “but toxicity is not trivial, so the long-term data will provide better clarity as to the degree of benefit.”
 

Ongoing responses at 9 months

The phase 2 ZUMA-12 study includes patients classified as high risk based on MYC and BCL2 and/or BCL6 translocations, or by an International Prognostic Indicator score of 3 or greater.

Patients initially received two cycles of anti-CD20 monoclonal antibody therapy plus an anthracycline containing regimen. Those with a positive interim PET (score of 4 or 5 on the 5-point Deauville scale) received fludarabine/cyclophosphamide conditioning plus axi-cel as a single intravenous infusion of 2 x 106 CAR T cells per kg of body weight.

As of the report at the ASH meeting, 32 patient had received axi-cel, of whom 32 were evaluable for safety and 27 were evaluable for efficacy.

The ORR was 85% (23 of 27 patients), and the CR rate was 74% (20 of 27 patients), Dr. Neelapu reported, noting that with a median follow-up of 9.3 months, 70% of responders (19 of 27) were in ongoing response.

Median duration of response, progression-free survival, and overall survival have not been reached, he added.

Encephalopathy was the most common grade 3 or greater adverse event related to axi-cel, occurring in 16% of patients, while increased alanine aminotransferase and decreased neutrophil count were each seen in 9% of patients, Dr. Neelapu said.

All 32 patients experienced CRS, including grade 3 CRS in 3 patients (9%), according to the reported data. Neurologic events were seen in 22 patients (69%) including grade 3 or greater in 8 (25%). There were 2 grade 4 neurologic events – both encephalopathies that resolved, according to Dr. Neelapu – and no grade 5 neurologic events.

ZUMA-12 is sponsored by Kite, a Gilead Company. Dr. Neelapu reported disclosures related to Acerta, Adicet Bio, Bristol-Myers Squibb, Kite, and various other pharmaceutical and biotechnology companies.
 

SOURCE: Neelapu SS et al. ASH 2020, Abstract 405.

Axicabtagene ciloleucel (axi-cel) can be safely administered and has substantial clinical benefit as part of first-line therapy in patients with high-risk large B-cell lymphoma, according to an investigator in a phase 2 study.

The chimeric antigen receptor (CAR) T-cell therapy had a “very high” overall response rate (ORR) of 85% and a complete response (CR) rate of 74% in the ZUMA-12 study, said investigator Sattva S. Neelapu, MD, of The University of Texas MD Anderson Cancer Center in Houston.

Nearly three-quarters of responses were ongoing with a median of follow-up of about 9 months, Dr. Neelapu said in interim analysis of ZUMA-12 presented at the annual meeting of the American Society of Hematology, which was held virtually.

While axi-cel is approved for treatment of certain relapsed/refractory large B-cell lymphomas (LBCLs), Dr. Neelapu said this is the first-ever study evaluating a CAR T-cell therapy as a first-line treatment for patients with LBCL that is high risk as defined by histology or International Prognostic Index (IPI) scoring.

Treatment with axi-cel was guided by dynamic risk assessment, Dr. Neelapu explained, meaning that patients received the CAR T-cell treatment if they had a positive interim positron emission tomography (PET) scan after two cycles of an anti-CD20 monoclonal antibody and anthracycline-containing regimen.
 

Longer follow-up needed

The interim efficacy analysis is based on 27 evaluable patients out of 40 patients planned to be enrolled, meaning that the final analysis is needed, and longer follow-up is needed to ensure that durability is maintained, Dr. Neelapu said in a question-and-answer session following his presentation.

Nevertheless, the 74% complete response rate in the frontline setting is “quite encouraging” compared to historical data in high-risk LBCL, where CR rates have generally been less than 50%, Dr. Neelapu added.

“Assuming that long-term data in the final analysis confirms this encouraging activity, I think we likely would need a randomized phase 3 trial to compare (axi-cel) head-to-head with frontline therapy,” he said.

Without mature data available, it’s hard to say in this single-arm study how much axi-cel is improving outcomes at the cost of significant toxicity, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

Adverse events as reported by Dr. Neelapu included grade 3 cytokine release syndrome (CRS) in 9% of patients, and 25% grade 3 or greater neurologic events in 25%.

“It appears as though it may be salvaging some patients, as the response rate is higher than that expected for chemotherapy alone in this setting,” Dr. Diefenbach said in an interview, “but toxicity is not trivial, so the long-term data will provide better clarity as to the degree of benefit.”
 

Ongoing responses at 9 months

The phase 2 ZUMA-12 study includes patients classified as high risk based on MYC and BCL2 and/or BCL6 translocations, or by an International Prognostic Indicator score of 3 or greater.

Patients initially received two cycles of anti-CD20 monoclonal antibody therapy plus an anthracycline containing regimen. Those with a positive interim PET (score of 4 or 5 on the 5-point Deauville scale) received fludarabine/cyclophosphamide conditioning plus axi-cel as a single intravenous infusion of 2 x 106 CAR T cells per kg of body weight.

As of the report at the ASH meeting, 32 patient had received axi-cel, of whom 32 were evaluable for safety and 27 were evaluable for efficacy.

The ORR was 85% (23 of 27 patients), and the CR rate was 74% (20 of 27 patients), Dr. Neelapu reported, noting that with a median follow-up of 9.3 months, 70% of responders (19 of 27) were in ongoing response.

Median duration of response, progression-free survival, and overall survival have not been reached, he added.

Encephalopathy was the most common grade 3 or greater adverse event related to axi-cel, occurring in 16% of patients, while increased alanine aminotransferase and decreased neutrophil count were each seen in 9% of patients, Dr. Neelapu said.

All 32 patients experienced CRS, including grade 3 CRS in 3 patients (9%), according to the reported data. Neurologic events were seen in 22 patients (69%) including grade 3 or greater in 8 (25%). There were 2 grade 4 neurologic events – both encephalopathies that resolved, according to Dr. Neelapu – and no grade 5 neurologic events.

ZUMA-12 is sponsored by Kite, a Gilead Company. Dr. Neelapu reported disclosures related to Acerta, Adicet Bio, Bristol-Myers Squibb, Kite, and various other pharmaceutical and biotechnology companies.
 

SOURCE: Neelapu SS et al. ASH 2020, Abstract 405.

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with sequential blinatumomab is highly effective as frontline therapy for Philadelphia Chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (ALL), according to results of a phase 2 study reported at the annual meeting of the American Society of Hematology.

Favorable minimal residual disease (MRD) negativity and overall survival with low higher-grade toxicities suggest that reductions in chemotherapy in this setting are feasible, said Nicholas J. Short, MD, of the University of Texas MD Anderson Cancer Center, Houston.

While complete response rates with current ALL therapy are 80%-90%, long-term overall survival is only 40%-50%. Blinatumomab, a bispecific T-cell–engaging CD3-CD19 antibody, has been shown to be superior to chemotherapy in relapsed/refractory B-cell ALL, and to produce high rates of MRD eradication, the most important prognostic factor in ALL, Dr. Short said at the meeting, which was held virtually.

The hypothesis of the current study was that early incorporation of blinatumomab with hyper-CVAD in patients with newly diagnosed Ph-negative B-cell ALL would decrease the need for intensive chemotherapy and lead to higher efficacy and cure rates with less myelosuppression. Patients were required to have a performance status of 3 or less, total bilirubin 2 mg/dL or less and creatinine 2 mg/dL or less. Investigators enrolled 38 patients (mean age, 37 years,; range, 17-59) with most (79%) in performance status 0-1. The primary endpoint was relapse-free survival (RFS).
 

Study details

Patients received hyper-CVAD alternating with high-dose methotrexate and cytarabine for up to four cycles followed by four cycles of blinatumomab at standard doses. Those with CD20-positive disease (1% or greater percentage of the cells) received eight doses of ofatumumab or rituximab, and prophylactic intrathecal chemotherapy was given eight times in the first four cycles. Maintenance consisted of alternating blocks of POMP (6-mercaptopurine, vincristine, methotrexate, prednisone) and blinatumomab. When two patients with high-risk features experienced early relapse, investigators amended the protocol to allow blinatumomab after only two cycles of hyper-CVAD in those with high-risk features (e.g., CRLF2 positive by flow cytometry, complex karyotype, KMT2A rearranged, low hypodiploidy/near triploidy, TP53 mutation, or persistent MRD). Nineteen patients (56%) had at least one high-risk feature, and 82% received ofatumumab or rituximab. Six patients were in complete remission at the start of the study (four of them MRD negative).

Complete responses

After induction, complete responses were achieved in 81% (26/32), with all patients achieving a complete response at some point, according to Dr. Short. The MRD negativity rate was 71% (24/34) after induction and 97% (33/34) at any time. Among the 38 patients, all with complete response at median follow-up of 24 months (range, 2-45), relapses occurred only in those 5 patients with high-risk features. Twelve patients underwent transplant in the first remission. Two relapsed, both with high-risk features. The other 21 patients had ongoing complete responses.

RFS at 1- and 2-years was 80% and 71%, respectively. Five among seven relapses were without hematopoietic stem cell transplantation, and 2 were post HSCT. Two deaths occurred in patients with complete responses (one pulmonary embolism and one with post-HSCT complications). Overall survival at 1 and 2 years was 85% and 80%, respectively, with the 2-year rate comparable with prior reports for hyper-CVAD plus ofatumumab, Dr. Short said.

The most common nonhematologic grade 3-4 adverse events with hyper-CVAD plus blinatumomab were ALT/AST elevation (24%) and hyperglycemia (21%). The overall cytokine release syndrome rate was 13%, with 3% for higher-grade reactions. The rate for blinatumomab-related neurologic events was 45% overall and 13% for higher grades, with 1 discontinuation attributed to grade 2 encephalopathy and dysphasia.

“Overall, this study shows the potential benefit of incorporating frontline blinatumomab into the treatment of younger adults with newly diagnosed Philadelphia chromosome–negative B-cell lymphoma, and shows, as well, that reduction of chemotherapy in this context is feasible,” Dr. Short stated.

“Ultimately, often for any patients with acute leukemias and ALL, our only chance to cure them is in the frontline setting, so our approach is to include all of the most effective agents we have. So that means including blinatumomab in all of our frontline regimens in clinical trials – and now we’ve amended that to add inotuzumab ozogamicin with the goal of deepening responses and increasing cure rates,” he added.

Dr. Short reported consulting with Takeda Oncology and Astrazeneca, and receiving research funding and honoraria from Amgen, Astella, and Takeda Oncology.

SOURCE: Short NG et al. ASH 2020, Abstract 464.

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with sequential blinatumomab is highly effective as frontline therapy for Philadelphia Chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (ALL), according to results of a phase 2 study reported at the annual meeting of the American Society of Hematology.

Favorable minimal residual disease (MRD) negativity and overall survival with low higher-grade toxicities suggest that reductions in chemotherapy in this setting are feasible, said Nicholas J. Short, MD, of the University of Texas MD Anderson Cancer Center, Houston.

While complete response rates with current ALL therapy are 80%-90%, long-term overall survival is only 40%-50%. Blinatumomab, a bispecific T-cell–engaging CD3-CD19 antibody, has been shown to be superior to chemotherapy in relapsed/refractory B-cell ALL, and to produce high rates of MRD eradication, the most important prognostic factor in ALL, Dr. Short said at the meeting, which was held virtually.

The hypothesis of the current study was that early incorporation of blinatumomab with hyper-CVAD in patients with newly diagnosed Ph-negative B-cell ALL would decrease the need for intensive chemotherapy and lead to higher efficacy and cure rates with less myelosuppression. Patients were required to have a performance status of 3 or less, total bilirubin 2 mg/dL or less and creatinine 2 mg/dL or less. Investigators enrolled 38 patients (mean age, 37 years,; range, 17-59) with most (79%) in performance status 0-1. The primary endpoint was relapse-free survival (RFS).
 

Study details

Patients received hyper-CVAD alternating with high-dose methotrexate and cytarabine for up to four cycles followed by four cycles of blinatumomab at standard doses. Those with CD20-positive disease (1% or greater percentage of the cells) received eight doses of ofatumumab or rituximab, and prophylactic intrathecal chemotherapy was given eight times in the first four cycles. Maintenance consisted of alternating blocks of POMP (6-mercaptopurine, vincristine, methotrexate, prednisone) and blinatumomab. When two patients with high-risk features experienced early relapse, investigators amended the protocol to allow blinatumomab after only two cycles of hyper-CVAD in those with high-risk features (e.g., CRLF2 positive by flow cytometry, complex karyotype, KMT2A rearranged, low hypodiploidy/near triploidy, TP53 mutation, or persistent MRD). Nineteen patients (56%) had at least one high-risk feature, and 82% received ofatumumab or rituximab. Six patients were in complete remission at the start of the study (four of them MRD negative).

Complete responses

After induction, complete responses were achieved in 81% (26/32), with all patients achieving a complete response at some point, according to Dr. Short. The MRD negativity rate was 71% (24/34) after induction and 97% (33/34) at any time. Among the 38 patients, all with complete response at median follow-up of 24 months (range, 2-45), relapses occurred only in those 5 patients with high-risk features. Twelve patients underwent transplant in the first remission. Two relapsed, both with high-risk features. The other 21 patients had ongoing complete responses.

RFS at 1- and 2-years was 80% and 71%, respectively. Five among seven relapses were without hematopoietic stem cell transplantation, and 2 were post HSCT. Two deaths occurred in patients with complete responses (one pulmonary embolism and one with post-HSCT complications). Overall survival at 1 and 2 years was 85% and 80%, respectively, with the 2-year rate comparable with prior reports for hyper-CVAD plus ofatumumab, Dr. Short said.

The most common nonhematologic grade 3-4 adverse events with hyper-CVAD plus blinatumomab were ALT/AST elevation (24%) and hyperglycemia (21%). The overall cytokine release syndrome rate was 13%, with 3% for higher-grade reactions. The rate for blinatumomab-related neurologic events was 45% overall and 13% for higher grades, with 1 discontinuation attributed to grade 2 encephalopathy and dysphasia.

“Overall, this study shows the potential benefit of incorporating frontline blinatumomab into the treatment of younger adults with newly diagnosed Philadelphia chromosome–negative B-cell lymphoma, and shows, as well, that reduction of chemotherapy in this context is feasible,” Dr. Short stated.

“Ultimately, often for any patients with acute leukemias and ALL, our only chance to cure them is in the frontline setting, so our approach is to include all of the most effective agents we have. So that means including blinatumomab in all of our frontline regimens in clinical trials – and now we’ve amended that to add inotuzumab ozogamicin with the goal of deepening responses and increasing cure rates,” he added.

Dr. Short reported consulting with Takeda Oncology and Astrazeneca, and receiving research funding and honoraria from Amgen, Astella, and Takeda Oncology.

SOURCE: Short NG et al. ASH 2020, Abstract 464.

Hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) with sequential blinatumomab is highly effective as frontline therapy for Philadelphia Chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (ALL), according to results of a phase 2 study reported at the annual meeting of the American Society of Hematology.

Favorable minimal residual disease (MRD) negativity and overall survival with low higher-grade toxicities suggest that reductions in chemotherapy in this setting are feasible, said Nicholas J. Short, MD, of the University of Texas MD Anderson Cancer Center, Houston.

While complete response rates with current ALL therapy are 80%-90%, long-term overall survival is only 40%-50%. Blinatumomab, a bispecific T-cell–engaging CD3-CD19 antibody, has been shown to be superior to chemotherapy in relapsed/refractory B-cell ALL, and to produce high rates of MRD eradication, the most important prognostic factor in ALL, Dr. Short said at the meeting, which was held virtually.

The hypothesis of the current study was that early incorporation of blinatumomab with hyper-CVAD in patients with newly diagnosed Ph-negative B-cell ALL would decrease the need for intensive chemotherapy and lead to higher efficacy and cure rates with less myelosuppression. Patients were required to have a performance status of 3 or less, total bilirubin 2 mg/dL or less and creatinine 2 mg/dL or less. Investigators enrolled 38 patients (mean age, 37 years,; range, 17-59) with most (79%) in performance status 0-1. The primary endpoint was relapse-free survival (RFS).
 

Study details

Patients received hyper-CVAD alternating with high-dose methotrexate and cytarabine for up to four cycles followed by four cycles of blinatumomab at standard doses. Those with CD20-positive disease (1% or greater percentage of the cells) received eight doses of ofatumumab or rituximab, and prophylactic intrathecal chemotherapy was given eight times in the first four cycles. Maintenance consisted of alternating blocks of POMP (6-mercaptopurine, vincristine, methotrexate, prednisone) and blinatumomab. When two patients with high-risk features experienced early relapse, investigators amended the protocol to allow blinatumomab after only two cycles of hyper-CVAD in those with high-risk features (e.g., CRLF2 positive by flow cytometry, complex karyotype, KMT2A rearranged, low hypodiploidy/near triploidy, TP53 mutation, or persistent MRD). Nineteen patients (56%) had at least one high-risk feature, and 82% received ofatumumab or rituximab. Six patients were in complete remission at the start of the study (four of them MRD negative).

Complete responses

After induction, complete responses were achieved in 81% (26/32), with all patients achieving a complete response at some point, according to Dr. Short. The MRD negativity rate was 71% (24/34) after induction and 97% (33/34) at any time. Among the 38 patients, all with complete response at median follow-up of 24 months (range, 2-45), relapses occurred only in those 5 patients with high-risk features. Twelve patients underwent transplant in the first remission. Two relapsed, both with high-risk features. The other 21 patients had ongoing complete responses.

RFS at 1- and 2-years was 80% and 71%, respectively. Five among seven relapses were without hematopoietic stem cell transplantation, and 2 were post HSCT. Two deaths occurred in patients with complete responses (one pulmonary embolism and one with post-HSCT complications). Overall survival at 1 and 2 years was 85% and 80%, respectively, with the 2-year rate comparable with prior reports for hyper-CVAD plus ofatumumab, Dr. Short said.

The most common nonhematologic grade 3-4 adverse events with hyper-CVAD plus blinatumomab were ALT/AST elevation (24%) and hyperglycemia (21%). The overall cytokine release syndrome rate was 13%, with 3% for higher-grade reactions. The rate for blinatumomab-related neurologic events was 45% overall and 13% for higher grades, with 1 discontinuation attributed to grade 2 encephalopathy and dysphasia.

“Overall, this study shows the potential benefit of incorporating frontline blinatumomab into the treatment of younger adults with newly diagnosed Philadelphia chromosome–negative B-cell lymphoma, and shows, as well, that reduction of chemotherapy in this context is feasible,” Dr. Short stated.

“Ultimately, often for any patients with acute leukemias and ALL, our only chance to cure them is in the frontline setting, so our approach is to include all of the most effective agents we have. So that means including blinatumomab in all of our frontline regimens in clinical trials – and now we’ve amended that to add inotuzumab ozogamicin with the goal of deepening responses and increasing cure rates,” he added.

Dr. Short reported consulting with Takeda Oncology and Astrazeneca, and receiving research funding and honoraria from Amgen, Astella, and Takeda Oncology.

SOURCE: Short NG et al. ASH 2020, Abstract 464.

The federal government says it will distribute only enough doses of Pfizer’s COVID-19 vaccine to immunize 2.9 million Americans in the first week after the US Food and Drug Administration (FDA) authorizes it, far less than the initially discussed 6.4 million doses.

Theoretically, states have already formulated plans for distribution based on the revised lower amount. But in a briefing with reporters on December 9, officials from Operation Warp Speed and the Department of Health and Human Services (HHS) didn’t make clear exactly what the states were expecting.

Vaccine will be shipped to and allocated by 64 jurisdictions and five federal agencies — the Bureau of Prisons, the Department of Defense, the Department of State, the Indian Health Service, and the Veterans Health Administration — according to the Centers for Disease Control and Prevention’s COVID-19 Vaccination Program Interim Playbook.

It will be up to states — which will receive a supply prorated to population — and these agencies to determine how to prioritize distribution of the 2.9 million doses. Each state and agency has its own plan. Gen. Gustave Perna, the chief operating officer for Operation Warp Speed, said in the briefing that 30 states have told the federal government they will prioritize initial doses for residents and staff of long-term care facilities.

The distribution is contingent on FDA authorization, which could happen soon. The FDA’s Vaccines and Related Biologics Advisory Committee weighed the effectiveness data for the Pfizer vaccine on December 10 and recommended that the agency grant emergency authorization. The FDA could issue a decision at any time.
 

Fewer doses out of the gate

Perna said the federal government will begin shipping the Pfizer vaccine within 24 hours of an FDA authorization.

He said those shipments will include a total of 2.9 million doses — not the 6.4 million that will be available. The government is holding 500,000 doses in reserve and another 2.9 million to guarantee that the first few million people who are vaccinated will be able to receive a second dose 21 days later, said Perna.

In part, that is because the FDA labeling will require that a first dose be followed by a second exactly 21 days later, said HHS Secretary Alex Azar in the briefing.

Federal officials have calculated how much to hold back on the basis of Pfizer’s production, said Azar. At least initially, “we will not distribute a vaccine knowing that the booster will not be available either from reserve supply by us or ongoing expected predicted production,” he said.

Even with Pfizer having reduced its estimates of how much vaccine it can deliver in December, Azar said, “There will be enough vaccine available for 20 million first vaccinations in the month of December.”

That estimate is predicated, however, on the idea that a vaccine under development by Moderna will receive clearance shortly after the FDA assesses that vaccine’s safety and effectiveness on December 17.

This article first appeared on Medscape.com.

The federal government says it will distribute only enough doses of Pfizer’s COVID-19 vaccine to immunize 2.9 million Americans in the first week after the US Food and Drug Administration (FDA) authorizes it, far less than the initially discussed 6.4 million doses.

Theoretically, states have already formulated plans for distribution based on the revised lower amount. But in a briefing with reporters on December 9, officials from Operation Warp Speed and the Department of Health and Human Services (HHS) didn’t make clear exactly what the states were expecting.

Vaccine will be shipped to and allocated by 64 jurisdictions and five federal agencies — the Bureau of Prisons, the Department of Defense, the Department of State, the Indian Health Service, and the Veterans Health Administration — according to the Centers for Disease Control and Prevention’s COVID-19 Vaccination Program Interim Playbook.

It will be up to states — which will receive a supply prorated to population — and these agencies to determine how to prioritize distribution of the 2.9 million doses. Each state and agency has its own plan. Gen. Gustave Perna, the chief operating officer for Operation Warp Speed, said in the briefing that 30 states have told the federal government they will prioritize initial doses for residents and staff of long-term care facilities.

The distribution is contingent on FDA authorization, which could happen soon. The FDA’s Vaccines and Related Biologics Advisory Committee weighed the effectiveness data for the Pfizer vaccine on December 10 and recommended that the agency grant emergency authorization. The FDA could issue a decision at any time.
 

Fewer doses out of the gate

Perna said the federal government will begin shipping the Pfizer vaccine within 24 hours of an FDA authorization.

He said those shipments will include a total of 2.9 million doses — not the 6.4 million that will be available. The government is holding 500,000 doses in reserve and another 2.9 million to guarantee that the first few million people who are vaccinated will be able to receive a second dose 21 days later, said Perna.

In part, that is because the FDA labeling will require that a first dose be followed by a second exactly 21 days later, said HHS Secretary Alex Azar in the briefing.

Federal officials have calculated how much to hold back on the basis of Pfizer’s production, said Azar. At least initially, “we will not distribute a vaccine knowing that the booster will not be available either from reserve supply by us or ongoing expected predicted production,” he said.

Even with Pfizer having reduced its estimates of how much vaccine it can deliver in December, Azar said, “There will be enough vaccine available for 20 million first vaccinations in the month of December.”

That estimate is predicated, however, on the idea that a vaccine under development by Moderna will receive clearance shortly after the FDA assesses that vaccine’s safety and effectiveness on December 17.

This article first appeared on Medscape.com.

The federal government says it will distribute only enough doses of Pfizer’s COVID-19 vaccine to immunize 2.9 million Americans in the first week after the US Food and Drug Administration (FDA) authorizes it, far less than the initially discussed 6.4 million doses.

Theoretically, states have already formulated plans for distribution based on the revised lower amount. But in a briefing with reporters on December 9, officials from Operation Warp Speed and the Department of Health and Human Services (HHS) didn’t make clear exactly what the states were expecting.

Vaccine will be shipped to and allocated by 64 jurisdictions and five federal agencies — the Bureau of Prisons, the Department of Defense, the Department of State, the Indian Health Service, and the Veterans Health Administration — according to the Centers for Disease Control and Prevention’s COVID-19 Vaccination Program Interim Playbook.

It will be up to states — which will receive a supply prorated to population — and these agencies to determine how to prioritize distribution of the 2.9 million doses. Each state and agency has its own plan. Gen. Gustave Perna, the chief operating officer for Operation Warp Speed, said in the briefing that 30 states have told the federal government they will prioritize initial doses for residents and staff of long-term care facilities.

The distribution is contingent on FDA authorization, which could happen soon. The FDA’s Vaccines and Related Biologics Advisory Committee weighed the effectiveness data for the Pfizer vaccine on December 10 and recommended that the agency grant emergency authorization. The FDA could issue a decision at any time.
 

Fewer doses out of the gate

Perna said the federal government will begin shipping the Pfizer vaccine within 24 hours of an FDA authorization.

He said those shipments will include a total of 2.9 million doses — not the 6.4 million that will be available. The government is holding 500,000 doses in reserve and another 2.9 million to guarantee that the first few million people who are vaccinated will be able to receive a second dose 21 days later, said Perna.

In part, that is because the FDA labeling will require that a first dose be followed by a second exactly 21 days later, said HHS Secretary Alex Azar in the briefing.

Federal officials have calculated how much to hold back on the basis of Pfizer’s production, said Azar. At least initially, “we will not distribute a vaccine knowing that the booster will not be available either from reserve supply by us or ongoing expected predicted production,” he said.

Even with Pfizer having reduced its estimates of how much vaccine it can deliver in December, Azar said, “There will be enough vaccine available for 20 million first vaccinations in the month of December.”

That estimate is predicated, however, on the idea that a vaccine under development by Moderna will receive clearance shortly after the FDA assesses that vaccine’s safety and effectiveness on December 17.

This article first appeared on Medscape.com.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Federal advisers on Thursday told US regulators that the benefits of Pfizer's COVID vaccine outweigh its risks for people aged 16 years and older, moving this product closer to a special emergency clearance. 

The US Food and Drug Administration (FDA) put Pfizer's application before its Vaccines and Related Biological Products Advisory Committee (VRBPAC), seeking expert feedback on what is likely to be the first COVID-19 vaccine cleared for use in the United States.

New York-based Pfizer is seeking an emergency use authorization (EUA) for its vaccine, known as BNT162b2, which it developed with Germany's BioNTech. The FDA asked its advisers to vote on a single question regarding this product: "Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?"

The members of VRBPAC voted 17-4 in favor of the Pfizer vaccine, with one panelist abstaining. The FDA considers the recommendations of its panels, but is not bound by them. The agency is expected to quickly grant the special clearance to Pfizer's vaccine, with the company then expected to complete work needed for a more complete biologics license application (BLA).

The FDA often allows members of its advisory committees to explain the reasons for their decisions to vote for or against an application after the tallies are publicly counted.

But the FDA did not give VRBPAC members this opportunity on Thursday, leaving the public without detailed insight into their support or objections.

Before the vote, several panelists had asked if the FDA could rephrase the voting question, raising the age for the approved group to perhaps 18 years of age. During the day, panelists also had questioned whether Pfizer's studies give enough information to judge whether the vaccine works against severe cases of COVID. And there was a discussion about how Pfizer could address concerns about the potential for allergic reactions to the vaccine, given the news of two healthcare workers who experienced allergic reactions after having the vaccine but who have since recovered.

In closing the meeting, VRBPAC chairman, Arnold Monto, MD, noted that the panel will on Dec. 17 meet again to offer recommendations on Moderna Inc.'s COVID vaccine.

"I believe most of us are going to be revisiting some of these issues in about a week," he said.

The panelist who abstained was H. Cody Meissner, MD, an expert in pediatric infectious disease from Tufts University. He earlier was among the several panelists who raised questions about the limited data available about the benefit to those ages 16 and 17. Those voting against the application were Michael Kurilla, MD, PhD; Archana Chatterjee, MD, PhD; A. Oveta Fuller, PhD, and David Kim, MD, MA, according to a tally read by the FDA staff after the vote.

Meanwhile, Sheldon Toubman, JD, voted in favor of the application according to the FDA staff's tally. Toubman had been a chief critic among VRBPAC members in reviewing Pfizer's application at the meeting. He'd suggested limiting the EUA to healthcare workers and residents of nursing homes. Members of these two groups are expected to be the first in the US to get Pfizer's vaccine, for which there will be only a limited initial supply. That idea gained no traction.

Toubman also pressed for more evidence that Pfizer's vaccine will work against severe cases of COVID.

The FDA staff on December 8 released a largely positive agency review of Pfizer vaccine. The efficacy of a two-dose administration of the vaccine has been pegged at 95.0%, with eight COVID-19 cases in the vaccine group and 162 COVID-19 cases in the placebo group. The FDA staff said that the 95% credible interval for the vaccine efficacy was 90.3% to 97.6%.

In that review, the FDA staff said there may be a hint from the results observed to date that the Pfizer vaccine may help ward off severe cases of COVID-19. There were 10 study participants that had severe COVID-19 disease after the first dose: one who received the vaccine and nine who received placebo.

"The total number of severe cases is small, which limits the overall conclusions that can be drawn; however, the case split does suggest protection from severe COVID-19 disease," the FDA staff said.

At the meeting today, Doron Fink, MD, PhD, a lead FDA official on the COVID vaccine review, responded directly to Toubman's concerns. There are many examples of vaccines that protect as well if not better against severe disease as they do against mild to moderate disease, Fink said.

"Protecting against disease of any severity is actually a pretty good predictor of protection against severe disease," Fink said, adding that there's already been a "strong result" shown in terms of the efficacy of Pfizer's vaccine.

Rolling out

Canadian health regulators on December 9 announced their nation's conditional approval of Pfizer's vaccine for people ages 16 and older.  In the United Kingdom, a widely publicized rollout of Pfizer's vaccine began on Dec. 8. News quickly spread about two workers in the National Health Service having allergic reactions following vaccination. Both of these workers carry adrenaline autoinjectors, suggesting they have suffered reactions in the past, the Guardian reported. These kinds of autoinjectors are well known in the United States under the brand name EpiPen.

A noted vaccine expert serving on VRBPAC, Paul Offit, MD, of Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, urged the FDA and Pfizer to investigate any connection between reaction to the vaccine and known allergies. If not fully addressed, reports of the reactions seen in initial vaccinations in the UK could prove to unnecessarily frighten people who have allergies away from getting the COVID shot, he said.

Offit suggested running tests where people with egg and peanut allergies would get the Pfizer vaccine under close medical observation "to prove that this is not going to be a problem."

"This is a practical solution because this issue is not going to die until we have better data," Offit said.

More than a dozen COVID-19 vaccines have reached advanced stages of testing, including ones developed in Russia and China, according to the World Health Organization (WHO). The two leading candidates for the US market are the Pfizer/BioNTech vaccine and a similar vaccine developed by Moderna and the National Institute of Allergy and Infectious Diseases. Johnson & Johnson and AstraZeneca are among the other companies with COVID-19 vaccines in testing.

The rapid development of COVID vaccines will create challenges in testing these products. A key issue will be how and whether to continue with placebo-controlled trials, even though such research would be helpful, FDA advisers said.

The FDA tasked Steven Goodman, MD, MHS, PhD, of Stanford University with presenting an overview of considerations for continuing a placebo-controlled trial as COVID vaccines become available. Once a COVID-19 vaccine becomes available to the public, people who have received placebo in the Pfizer trial should not be allowed to immediately receive the vaccine, Goodman said.

There isn't a strong medically-based argument against placebo-controlled research in COVID-19, as many people can take steps to reduce their risk for the infection, Goodman said.

"So as long as there are still important things to learn about the vaccine, placebo-controlled trials should not be regarded as unethical," Goodman said. " I think, however, they might be infeasible. And that is a big issue, because people may not be willing to either remain in the study or to enroll."

During the public comment session, a former FDA official spoke of a need for careful consideration of study volunteers' needs in designing trials of COVID-19 vaccines.

"Reasonable people can disagree over whether study subjects should have priority access to a product whose efficacy they helped demonstrate," said Peter Lurie, MD, president of the nonprofit Center for Science in the Public Interest. "But we ought to be able to agree on this: No subject who has put their body on the line in a vaccine study should be at a disadvantage in terms of vaccine access as a result of their participation."

Lurie argued against extended periods of blinded follow-up after authorization of a COVID-19 vaccine. Such a requirement would be "hard to justify ethically, if it is inconsistent with public health recommendations, particularly with rapidly rising case rates and the reported levels of effectiveness" of the Pfizer vaccine, said Lurie, who served as an associate commissioner at FDA from 2014 to 2017.

Lurie also noted the FDA staff's identification of what he called "disproportionate numbers of Bell's Palsy cases (4 in the vaccine groups vs. 0 in the placebo group)" as a matter that should continue to be monitored, including in the postmarketing phase. He raised no objections to the EUA.

Sidney Wolfe, MD, founder and senior adviser to Public Citizen's Health Research Group, also spoke at the public comment session, citing no objection to an EUA for the Pfizer vaccine. Like Lurie, he urged special consideration of people who have or will receive placebo in COVID-19 vaccine trials.

The Thursday advisory committee on the Pfizer vaccine differed from those held for many other products. The discussion focused more on how to monitor and evaluate the vaccine once approved, while advisory committees sometimes include a detailed look at whether a company has proven that its product works. One of the special advisers serving temporarily on VRBPAC, Eric J. Rubin, MD, PhD, also today published an editorial in The New England Journal of Medicine, titled "SARS-CoV-2 Vaccination — An Ounce (Actually, Much Less) of Prevention."

In the editorial, Rubin and coauthor, Dan L. Longo, MD, called the Pfizer vaccine results seen so far "impressive."

"In the primary analysis, only 8 cases of Covid-19 were seen in the vaccine group, as compared with 162 in the placebo group, for an overall efficacy of 95% (with a 95% credible interval of 90.3 to 97.6%)," they write. "Although the trial does not have the statistical power to assess subgroups, efficacy appeared to be similar in low-risk and high-risk persons, including some from communities that have been disproportionately affected by disease, and in participants older than 55 years of age and those younger than 55."

Intense Scrutiny

The FDA has come under intense scrutiny this year in part because of the aggressive — and ultimately unrealistic — timelines for COVID-19 treatments promoted by the Trump administration. President Donald Trump several times suggested a COVID-19 vaccine could be approved before the November election. Many concerned physicians and scientists including Medscape Editor-in-Chief Eric Topol, MD, called on FDA staff to fight back against any bid to inappropriately speed the approval process for political reasons.

"Any shortcuts will not only jeopardize the vaccine programs but betray the public trust, which is already fragile about vaccines, and has been made more so by your lack of autonomy from the Trump administration and its overt politicization of the FDA," Topol wrote in an August open letter to FDA Commissioner Stephen Hahn, MD.

In an October interview with Topol, Hahn noted that there has been some pushback against the idea of an EUA for a COVID-19 vaccine, with some people preferring to wait for a more complete biological license application.

"When you're talking about a pandemic where people are dying, you want to expedite it as much as possible," Hahn told Topol in the interview.

On Thursday, Hahn issued a public statement about the VRBPAC meeting. Hahn said the FDA's "career staff — made up of physicians, biologists, chemists, epidemiologists, statisticians, and other professionals — have been working around the clock to thoroughly evaluate the data and information in the EUA request."

"I can assure you that no vaccine will be authorized for use in the United States until FDA career officials feel confident in allowing their own families to receive it," Hahn said.

Many clinicians offered their views on the FDA meeting during the day on Twitter.

Robert Wachter, MD, chair of the Department of Medicine at the University of California, San Francisco, who has been a vocal opponent of some of Trump's public statements on COVID-19, urged state officials to stick with the FDA's call on the Pfizer vaccine. In a tweet, he noted that officials in California and several other states have called for independent reviews of COVID-19 vaccines.

If such reviews were to delay distribution of vaccines, this would "lead to more harm than good," Wachter tweeted. "Once FDA says 'go', we should go."

This article was updated 12/10/20.

This article originally appeared on Medscape.com.

Adolescents and young adults with aggressive mature B-cell non-Hodgkin lymphomas appear to have better outcomes when they’re treated under pediatric protocols rather than adult regimens, Canadian investigators say.

Results of a study of patients from the ages of 15 to 21 years with either diffuse large B-cell lymphoma (DLBCL) or Burkitt’s lymphoma treated at regional or community cancer centers in the province of Ontario indicated that adolescents and young adult (AYA) patients treated at adult centers had a more than fourfold risk for disease relapse or progression, compared with their counterparts who were treated at pediatric centers, reported Sumit Gupta, MD, PhD, from the Hospital for Sick Children in Toronto and colleagues.

“Our data suggest that pediatric approaches are associated with improved event-free survival and overall survival, primarily due to a decrease in the risk of relapse or progression, while still using lower cumulative doses of chemotherapy,” he said in an oral abstract presented at the American Society of Hematology annual meeting, held virtually.

The findings echo those seen in the treatment of patients with acute lymphoblastic leukemia (ALL). As previously reported, a study from Nordic and Baltic countries showed that young adults with ALL who were treated with a pediatric regimen had a 4-year event-free survival rate of 73%, compared with 42% for historical controls.

Similarly, a prospective U.S. study reported in 2014 showed that AYA with ALL treated with a pediatric regimen had better overall and event-free survival rates, compared with historical controls.

As with ALL, pediatric and adult regimens for treatment of patients with aggressive mature B-cell NHL differ substantially, with pediatric patients receiving more intensive short-term therapy with lower cumulative doses.

In addition, while pediatric regimens for DLBCL and Burkitt’s lymphoma are identical, adult regimens differ substantially between the two histologies, Dr. Gupta pointed out.

Adult regimens for DLBCL most often incorporate CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP), whereas Burkitt’s lymphoma in adults is generally treated with more aggressive multidrug regimens, in combination with rituximab.

Rituximab was incorporated into adults’ regimens far earlier than in pediatric regimens, with Food and Drug Administration approval of rituximab in frontline therapy of adults with DLBCL in 2006, “whereas the first pediatric large-scale randomized controlled trial of rituximab in pediatric mature B-cell lymphoma was only published earlier this year,” he noted.
 

Population-based study

To see how treatment patterns for AYA patients with aggressive mature B-cell non-Hodgkin lymphomas differ between pediatric and adult centers, Dr. Gupta and colleagues conducted a population-based study of all AYA in Ontario diagnosed with Burkitt’s or DLBCL from the ages of 15 to 21 years from 1992 through 2012.

AYA from the ages of 15 to 18 years who were treated at pediatric centers were identified through the Provincial Pediatric Oncology Registry, which includes data on demographics, disease treatment, and outcomes from each of Ontario’s five childhood cancer treatments centers.

Adolescents and young adults from 15 to 21 years who were treated at adult centers with adult regimens were identified through the Ontario Cancer Registry using chart abstraction by trained personnel at all treatment centers, with all data validated by clinician reviewers.

A total of 176 patients were identified, 129 with DLBCL and 47 with Burkitt’s lymphoma. In all, 62 of the 176 patients (35.2%) were treated in pediatric centers. Not surprisingly, multivariable analysis showed that AYA treated in adult centers were older, and more likely to have been treated earlier in the study period.

Comparing treatment patterns by locus of care, the investigators found that patients with DLBCL in pediatric centers received half of the cumulative anthracycline doses as those in adult centers (150 mg/m² vs. 300 mg/m²; P < .001) and about 75% of cumulative alkylating agent doses (3,300 mg/m² vs. 4,465 mg/m²; P = .009).

Patients with Burkitt’s lymphoma had identical exposures to anthracyclines in pediatric vs. adult centers (120 mg/m²), but those treated in pediatric centers had half the exposure to alkylators as those treated in adult centers (3,300 mg/m² vs. 6,600 mg/m²; P = .03).

Among patients with DLBCL, none of those treated at pediatric centers received rituximab, compared with 32.3% of those treated at adult centers (P < .001), whereas only a handful of patients with Burkitt’s lymphoma received rituximab in both pediatric and adult centers (nonsignificant).

Among all patients. 5-year event-free survival was 82.3% for those treated in pediatric centers, compared with 66.7% for those treated in adult centers (P = .02). Respective 5-year overall survival rates were 85.5% and 71.1% (P = .03).

Looking at survival by histology, the investigators saw that 5-year event-free survival for patients with DLBCL was 83.3% when they were treated like children vs. 66.7% when they were treated like adults (P = .04). Respective 5-year overall survival rates were 88.9% and 72% (P = .04).

Both event-free survival (80.8% vs. 66.7%) and overall survival (80.8% vs. 66.7%) were numerically but not statistically higher among patients with Burkitt’s treated at pediatric vs. adult centers.

An analysis adjusting for disease histology, stage, and time period of diagnosis showed that treatment at an adult center was associated with higher risk for death, with a hazard ratio of 2.4 (P = .03).

Additionally, an analysis adjusted for age, disease stage, and histology showed that patients treated in adult centers had a significantly increased risk of relapse or progression, compared with a HR of 4.4 (95% confidence interval; P = .008).

There were no significant differences in the risk of treatment-related mortality between the center types, however.

“It is important to note, however, that pediatric approaches to mature B-cell NHL [non-Hodgkin lymphoma] are associated with increased inpatient needs as compared to adult approaches, and with greater supportive care requirements. Thus the safety of such approaches in adults centers need to be established,” Dr. Gupta said.
 

Lower doses, better outcomes

In the question and answer session following the presentation, Jennifer Teichman, MD, MSc, a fellow in hematology at the University of Toronto who was not involved in the study asked why patients treated at adult centers would have higher relapse rates despite receiving higher doses of chemotherapy, noting that the poorer outcomes in those patients were not attributable to treatment-related mortality.

“I think one of the distinctions is that higher cumulative doses versus higher intensity of treatment over a shorter period of time are two different things, perhaps, and so giving lower cumulative doses but over a short period of time, and so giving higher intensity within that short period of time, may be what explains the higher success rate in pediatric trials,” Dr. Gupta said.

R. Michael Crump, MD, from the Princess Margaret Cancer Center, also in Toronto, asked whether the study results could have been influenced by differences between the pediatric center and adult center datasets in regard to pathology review, staging information, and International Prognostic Index.

Dr. Gupta acknowledged that, while the pediatric data were captured prospectively at each center by pediatric cancer registry staff and adult data were extracted retrospectively by trained chart reviewers, “the information that we were collecting was relatively basic – basic stage, basic histology, and that is a limitation.”

He also noted that clinicians reviewed the submitted retrospective data for completeness and had the ability to request chart extractors to return to a particular record for additional information or to correct potential errors.

The study was supported by the Canadian Institutes of Health Research, the C17 Council on Children’s Cancer & Blood Disorders, and the Pediatric Oncology Group of Ontario. Dr. Gupta, Dr. Teichman, and Dr. Crump all reported no relevant conflicts of interest.

SOURCE: Gupta S et al. ASH 2020, Abstract 708.

Adolescents and young adults with aggressive mature B-cell non-Hodgkin lymphomas appear to have better outcomes when they’re treated under pediatric protocols rather than adult regimens, Canadian investigators say.

Results of a study of patients from the ages of 15 to 21 years with either diffuse large B-cell lymphoma (DLBCL) or Burkitt’s lymphoma treated at regional or community cancer centers in the province of Ontario indicated that adolescents and young adult (AYA) patients treated at adult centers had a more than fourfold risk for disease relapse or progression, compared with their counterparts who were treated at pediatric centers, reported Sumit Gupta, MD, PhD, from the Hospital for Sick Children in Toronto and colleagues.

“Our data suggest that pediatric approaches are associated with improved event-free survival and overall survival, primarily due to a decrease in the risk of relapse or progression, while still using lower cumulative doses of chemotherapy,” he said in an oral abstract presented at the American Society of Hematology annual meeting, held virtually.

The findings echo those seen in the treatment of patients with acute lymphoblastic leukemia (ALL). As previously reported, a study from Nordic and Baltic countries showed that young adults with ALL who were treated with a pediatric regimen had a 4-year event-free survival rate of 73%, compared with 42% for historical controls.

Similarly, a prospective U.S. study reported in 2014 showed that AYA with ALL treated with a pediatric regimen had better overall and event-free survival rates, compared with historical controls.

As with ALL, pediatric and adult regimens for treatment of patients with aggressive mature B-cell NHL differ substantially, with pediatric patients receiving more intensive short-term therapy with lower cumulative doses.

In addition, while pediatric regimens for DLBCL and Burkitt’s lymphoma are identical, adult regimens differ substantially between the two histologies, Dr. Gupta pointed out.

Adult regimens for DLBCL most often incorporate CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP), whereas Burkitt’s lymphoma in adults is generally treated with more aggressive multidrug regimens, in combination with rituximab.

Rituximab was incorporated into adults’ regimens far earlier than in pediatric regimens, with Food and Drug Administration approval of rituximab in frontline therapy of adults with DLBCL in 2006, “whereas the first pediatric large-scale randomized controlled trial of rituximab in pediatric mature B-cell lymphoma was only published earlier this year,” he noted.
 

Population-based study

To see how treatment patterns for AYA patients with aggressive mature B-cell non-Hodgkin lymphomas differ between pediatric and adult centers, Dr. Gupta and colleagues conducted a population-based study of all AYA in Ontario diagnosed with Burkitt’s or DLBCL from the ages of 15 to 21 years from 1992 through 2012.

AYA from the ages of 15 to 18 years who were treated at pediatric centers were identified through the Provincial Pediatric Oncology Registry, which includes data on demographics, disease treatment, and outcomes from each of Ontario’s five childhood cancer treatments centers.

Adolescents and young adults from 15 to 21 years who were treated at adult centers with adult regimens were identified through the Ontario Cancer Registry using chart abstraction by trained personnel at all treatment centers, with all data validated by clinician reviewers.

A total of 176 patients were identified, 129 with DLBCL and 47 with Burkitt’s lymphoma. In all, 62 of the 176 patients (35.2%) were treated in pediatric centers. Not surprisingly, multivariable analysis showed that AYA treated in adult centers were older, and more likely to have been treated earlier in the study period.

Comparing treatment patterns by locus of care, the investigators found that patients with DLBCL in pediatric centers received half of the cumulative anthracycline doses as those in adult centers (150 mg/m² vs. 300 mg/m²; P < .001) and about 75% of cumulative alkylating agent doses (3,300 mg/m² vs. 4,465 mg/m²; P = .009).

Patients with Burkitt’s lymphoma had identical exposures to anthracyclines in pediatric vs. adult centers (120 mg/m²), but those treated in pediatric centers had half the exposure to alkylators as those treated in adult centers (3,300 mg/m² vs. 6,600 mg/m²; P = .03).

Among patients with DLBCL, none of those treated at pediatric centers received rituximab, compared with 32.3% of those treated at adult centers (P < .001), whereas only a handful of patients with Burkitt’s lymphoma received rituximab in both pediatric and adult centers (nonsignificant).

Among all patients. 5-year event-free survival was 82.3% for those treated in pediatric centers, compared with 66.7% for those treated in adult centers (P = .02). Respective 5-year overall survival rates were 85.5% and 71.1% (P = .03).

Looking at survival by histology, the investigators saw that 5-year event-free survival for patients with DLBCL was 83.3% when they were treated like children vs. 66.7% when they were treated like adults (P = .04). Respective 5-year overall survival rates were 88.9% and 72% (P = .04).

Both event-free survival (80.8% vs. 66.7%) and overall survival (80.8% vs. 66.7%) were numerically but not statistically higher among patients with Burkitt’s treated at pediatric vs. adult centers.

An analysis adjusting for disease histology, stage, and time period of diagnosis showed that treatment at an adult center was associated with higher risk for death, with a hazard ratio of 2.4 (P = .03).

Additionally, an analysis adjusted for age, disease stage, and histology showed that patients treated in adult centers had a significantly increased risk of relapse or progression, compared with a HR of 4.4 (95% confidence interval; P = .008).

There were no significant differences in the risk of treatment-related mortality between the center types, however.

“It is important to note, however, that pediatric approaches to mature B-cell NHL [non-Hodgkin lymphoma] are associated with increased inpatient needs as compared to adult approaches, and with greater supportive care requirements. Thus the safety of such approaches in adults centers need to be established,” Dr. Gupta said.
 

Lower doses, better outcomes

In the question and answer session following the presentation, Jennifer Teichman, MD, MSc, a fellow in hematology at the University of Toronto who was not involved in the study asked why patients treated at adult centers would have higher relapse rates despite receiving higher doses of chemotherapy, noting that the poorer outcomes in those patients were not attributable to treatment-related mortality.

“I think one of the distinctions is that higher cumulative doses versus higher intensity of treatment over a shorter period of time are two different things, perhaps, and so giving lower cumulative doses but over a short period of time, and so giving higher intensity within that short period of time, may be what explains the higher success rate in pediatric trials,” Dr. Gupta said.

R. Michael Crump, MD, from the Princess Margaret Cancer Center, also in Toronto, asked whether the study results could have been influenced by differences between the pediatric center and adult center datasets in regard to pathology review, staging information, and International Prognostic Index.

Dr. Gupta acknowledged that, while the pediatric data were captured prospectively at each center by pediatric cancer registry staff and adult data were extracted retrospectively by trained chart reviewers, “the information that we were collecting was relatively basic – basic stage, basic histology, and that is a limitation.”

He also noted that clinicians reviewed the submitted retrospective data for completeness and had the ability to request chart extractors to return to a particular record for additional information or to correct potential errors.

The study was supported by the Canadian Institutes of Health Research, the C17 Council on Children’s Cancer & Blood Disorders, and the Pediatric Oncology Group of Ontario. Dr. Gupta, Dr. Teichman, and Dr. Crump all reported no relevant conflicts of interest.

SOURCE: Gupta S et al. ASH 2020, Abstract 708.

Adolescents and young adults with aggressive mature B-cell non-Hodgkin lymphomas appear to have better outcomes when they’re treated under pediatric protocols rather than adult regimens, Canadian investigators say.

Results of a study of patients from the ages of 15 to 21 years with either diffuse large B-cell lymphoma (DLBCL) or Burkitt’s lymphoma treated at regional or community cancer centers in the province of Ontario indicated that adolescents and young adult (AYA) patients treated at adult centers had a more than fourfold risk for disease relapse or progression, compared with their counterparts who were treated at pediatric centers, reported Sumit Gupta, MD, PhD, from the Hospital for Sick Children in Toronto and colleagues.

“Our data suggest that pediatric approaches are associated with improved event-free survival and overall survival, primarily due to a decrease in the risk of relapse or progression, while still using lower cumulative doses of chemotherapy,” he said in an oral abstract presented at the American Society of Hematology annual meeting, held virtually.

The findings echo those seen in the treatment of patients with acute lymphoblastic leukemia (ALL). As previously reported, a study from Nordic and Baltic countries showed that young adults with ALL who were treated with a pediatric regimen had a 4-year event-free survival rate of 73%, compared with 42% for historical controls.

Similarly, a prospective U.S. study reported in 2014 showed that AYA with ALL treated with a pediatric regimen had better overall and event-free survival rates, compared with historical controls.

As with ALL, pediatric and adult regimens for treatment of patients with aggressive mature B-cell NHL differ substantially, with pediatric patients receiving more intensive short-term therapy with lower cumulative doses.

In addition, while pediatric regimens for DLBCL and Burkitt’s lymphoma are identical, adult regimens differ substantially between the two histologies, Dr. Gupta pointed out.

Adult regimens for DLBCL most often incorporate CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone) or CHOP plus rituximab (R-CHOP), whereas Burkitt’s lymphoma in adults is generally treated with more aggressive multidrug regimens, in combination with rituximab.

Rituximab was incorporated into adults’ regimens far earlier than in pediatric regimens, with Food and Drug Administration approval of rituximab in frontline therapy of adults with DLBCL in 2006, “whereas the first pediatric large-scale randomized controlled trial of rituximab in pediatric mature B-cell lymphoma was only published earlier this year,” he noted.
 

Population-based study

To see how treatment patterns for AYA patients with aggressive mature B-cell non-Hodgkin lymphomas differ between pediatric and adult centers, Dr. Gupta and colleagues conducted a population-based study of all AYA in Ontario diagnosed with Burkitt’s or DLBCL from the ages of 15 to 21 years from 1992 through 2012.

AYA from the ages of 15 to 18 years who were treated at pediatric centers were identified through the Provincial Pediatric Oncology Registry, which includes data on demographics, disease treatment, and outcomes from each of Ontario’s five childhood cancer treatments centers.

Adolescents and young adults from 15 to 21 years who were treated at adult centers with adult regimens were identified through the Ontario Cancer Registry using chart abstraction by trained personnel at all treatment centers, with all data validated by clinician reviewers.

A total of 176 patients were identified, 129 with DLBCL and 47 with Burkitt’s lymphoma. In all, 62 of the 176 patients (35.2%) were treated in pediatric centers. Not surprisingly, multivariable analysis showed that AYA treated in adult centers were older, and more likely to have been treated earlier in the study period.

Comparing treatment patterns by locus of care, the investigators found that patients with DLBCL in pediatric centers received half of the cumulative anthracycline doses as those in adult centers (150 mg/m² vs. 300 mg/m²; P < .001) and about 75% of cumulative alkylating agent doses (3,300 mg/m² vs. 4,465 mg/m²; P = .009).

Patients with Burkitt’s lymphoma had identical exposures to anthracyclines in pediatric vs. adult centers (120 mg/m²), but those treated in pediatric centers had half the exposure to alkylators as those treated in adult centers (3,300 mg/m² vs. 6,600 mg/m²; P = .03).

Among patients with DLBCL, none of those treated at pediatric centers received rituximab, compared with 32.3% of those treated at adult centers (P < .001), whereas only a handful of patients with Burkitt’s lymphoma received rituximab in both pediatric and adult centers (nonsignificant).

Among all patients. 5-year event-free survival was 82.3% for those treated in pediatric centers, compared with 66.7% for those treated in adult centers (P = .02). Respective 5-year overall survival rates were 85.5% and 71.1% (P = .03).

Looking at survival by histology, the investigators saw that 5-year event-free survival for patients with DLBCL was 83.3% when they were treated like children vs. 66.7% when they were treated like adults (P = .04). Respective 5-year overall survival rates were 88.9% and 72% (P = .04).

Both event-free survival (80.8% vs. 66.7%) and overall survival (80.8% vs. 66.7%) were numerically but not statistically higher among patients with Burkitt’s treated at pediatric vs. adult centers.

An analysis adjusting for disease histology, stage, and time period of diagnosis showed that treatment at an adult center was associated with higher risk for death, with a hazard ratio of 2.4 (P = .03).

Additionally, an analysis adjusted for age, disease stage, and histology showed that patients treated in adult centers had a significantly increased risk of relapse or progression, compared with a HR of 4.4 (95% confidence interval; P = .008).

There were no significant differences in the risk of treatment-related mortality between the center types, however.

“It is important to note, however, that pediatric approaches to mature B-cell NHL [non-Hodgkin lymphoma] are associated with increased inpatient needs as compared to adult approaches, and with greater supportive care requirements. Thus the safety of such approaches in adults centers need to be established,” Dr. Gupta said.
 

Lower doses, better outcomes

In the question and answer session following the presentation, Jennifer Teichman, MD, MSc, a fellow in hematology at the University of Toronto who was not involved in the study asked why patients treated at adult centers would have higher relapse rates despite receiving higher doses of chemotherapy, noting that the poorer outcomes in those patients were not attributable to treatment-related mortality.

“I think one of the distinctions is that higher cumulative doses versus higher intensity of treatment over a shorter period of time are two different things, perhaps, and so giving lower cumulative doses but over a short period of time, and so giving higher intensity within that short period of time, may be what explains the higher success rate in pediatric trials,” Dr. Gupta said.

R. Michael Crump, MD, from the Princess Margaret Cancer Center, also in Toronto, asked whether the study results could have been influenced by differences between the pediatric center and adult center datasets in regard to pathology review, staging information, and International Prognostic Index.

Dr. Gupta acknowledged that, while the pediatric data were captured prospectively at each center by pediatric cancer registry staff and adult data were extracted retrospectively by trained chart reviewers, “the information that we were collecting was relatively basic – basic stage, basic histology, and that is a limitation.”

He also noted that clinicians reviewed the submitted retrospective data for completeness and had the ability to request chart extractors to return to a particular record for additional information or to correct potential errors.

The study was supported by the Canadian Institutes of Health Research, the C17 Council on Children’s Cancer & Blood Disorders, and the Pediatric Oncology Group of Ontario. Dr. Gupta, Dr. Teichman, and Dr. Crump all reported no relevant conflicts of interest.

SOURCE: Gupta S et al. ASH 2020, Abstract 708.

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

Patients with cancer are at significantly increased risk for COVID-19 and worse outcomes, a new review confirms. It also found that patients with leukemia, non-Hodgkin lymphoma, and lung cancer are at greatest risk.

Blacks with cancer are at even higher risk, and for patients with colorectal cancer and non-Hodgkin lymphoma, the risk is higher for women than for men. (This contrasts with findings in noncancer populations, where men are more at risk from COVID-19 and severe outcomes than women.)

These findings come from a huge review of electronic health records of 73.4 million patients in the United States. They “highlight the need to protect and monitor patients with cancer as part of the strategy to control the pandemic,” the authors wrote.

The review was published online Dec. 10 in JAMA Oncology.

The greater risk for COVID-19 among patients with cancer is well known, but breaking the risk down by cancer type is novel, wrote the investigators, led by Quanqiu Wang, MS, Center for Artificial Intelligence in Drug Discovery, Case Western Reserve University, Cleveland.

Cancer patients are immunocompromised and have more contact with the health care system, which increases their risk for COVID-19. But which bodily systems are affected by cancer seems to matter. In patients with blood cancer, for example, COVID-19 is probably more dangerous, because blood cancer weakens the immune system directly, the authors suggested.

The increased risk for infection and hospitalization with SARS-CoV-2 among Black patients with cancer might be because of biology, but it is more likely because of factors that weren’t captured in the database review. Such factors include social adversity, economic status, access to health care, and lifestyle, the researchers noted.

For this study, the investigators analyzed electronic health records held in the IBM Watson Health Explorys system, which captures about 15% of new cancer diagnoses in the United States.

The analysis found that, as of Aug. 14, 2020, 16,570 patients (0.02%) had been diagnosed with COVID-19; about 1,200 also had been diagnosed with cancer. Of those, 690 were diagnosed with cancer in the previous year, which counted as a recent cancer diagnosis in the analysis. The study included 13 common cancers, including endometrial, kidney, liver, lung, gastrointestinal, prostate, skin, and thyroid cancers, among others.

Patients with any cancer diagnosis (adjusted odds ratio, 1.46) as well as those with a recent cancer diagnosis (aOR, 7.14) had a significantly higher risk for COVID-19 than those without cancer, after adjusting for asthma, cardiovascular diseases, nursing home stays, and other risk factors.

The risk for COVID-19 was highest among patients recently diagnosed with leukemia (aOR, 12.16), non-Hodgkin lymphoma (aOR, 8.54), and lung cancer (aOR 7.66). The risk for COVID-19 was lower for patients with cancers associated with worse prognoses, including pancreatic (aOR, 6.26) and liver (aOR, 6.49) cancer. It was weakest for patients with thyroid cancer (aOR, 3.10; P for all < .001).

Hospitalization was more common in recent cancer patients with COVID-19 than in COVID-19 patients without cancer (47.46% vs. 24.6%), as was COVID-19–related death (14.93% vs. 5.26%). Among cancer patients who did not have COVID-19, 12.39% were hospitalized, and 4.03% died. The findings suggest a synergistic effect between the COVID-19 and cancer, the team noted.

Among patients recently diagnosed with cancer, Black patients – 10.3% of the overall study population – had a significantly higher risk for COVID-19 than White patients. The racial disparity was largest for patients with breast cancer (aOR, 5.44), followed by patients with prostate cancer (aOR, 5.10), colorectal cancer (aOR, 3.30), and lung cancer (aOR, 2.53; P for all < .001).

Hospitalizations were more common among Black patients with cancer and COVID-19 than White patients. There was also a trend toward higher mortality among Black patients (18.52% vs. 13.51%; P = .11)

However, these differences may not be related to race, oncologist Aakash Desai, MBBS, of the Mayo Clinic, Rochester, Minn., and colleagues noted in an accompanying commentary. “Interestingly, a previous study of hospitalized patients with COVID-19 without cancer demonstrated that mortality rates for Black patients were comparable to those for White patients after adjustment for both comorbidities and deprivation index, suggesting that observed differences are mainly owing to societal disparities rather than biology.”

The editorialists also noted that the finding that Black patients with cancer are at greater risk for COVID-19 (aOR, 1.58-5.44, depending on cancer) echoes the findings in the general population. The Centers for Disease Control and Prevention estimates a severalfold increased risk among Black patients. These higher rates may largely be explained by social determinants, they suggested. Such factors include increased burden of comorbidities, crowded living conditions (inner cities, multigenerational homes, etc.), dependence on public transportation or child care, and higher work-related exposures. “Until such societal disparities are accounted for, we cannot presume these findings are caused by any inherent differences among racial groups,” the editorialists wrote.

“Clearly, the haunting spotlight of COVID-19 has dramatically illuminated known U.S. health care and societal disparities,” Dr. Desai and colleagues wrote. “This situation should be a wake-up call that brings much-needed improvements in U.S. equity policies, including but not limited to better health care access. Nothing appears more critical for alleviating these disparate clinical outcomes in this time of crisis and beyond,” they declared.

The study was funded by the National Institutes of Health, the American Cancer Society, and other organizations. The investigators disclosed having no relevant financial relationships.

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

The novel bispecific antibody odronextamab (REGN1979) is demonstrating encouraging activity, durable responses, and acceptable safety in a phase 1 study of patients with highly refractory B-cell non-Hodgkin lymphoma, according to an investigator.

Durable complete responses (CRs) to odronextamab are being observed in more than 80% of heavily pretreated patients with follicular lymphoma (FL) in the ongoing study, said Rajat Bannerji, MD, PhD, of Rutgers Cancer Institute of New Jersey, New Brunswick.

Likewise, durable CRs were seen in greater than 80% of patients diffuse large B-cell lymphoma (DLBCL) not previously exposed to chimeric antigen receptor (CAR) T-cell therapy, and also in about 20% of patients who were treated with CAR T cells, Dr. Bannerji reported at the annual meeting of the American Society of Hematology, held virtually this year.

For these patients with FL or DLBCL in the phase 1 study, cytokine release syndrome (CRS) and neurotoxicity events did not exceed grade 3 in severity, and no cases of tumor lysis syndrome (TLS) were observed, Dr. Bannerji added in his presentation.

Those findings suggest odronextamab, which binds to CD3 on T cells and CD20 on malignant B cells, may offer an “off-the-shelf, primarily outpatient treatment option” for patients with relapsed or refractory B-cell NHL, he said in concluding remarks on the study.

This first-in-human study took a conservative approach, according to Dr. Bannerji, by mandating hospital admission during an initial step-up dosing schedule used along with dexamethasone to mitigate risk of CRS.

“With our step-up dosing and steroid premedication, we really have not seen too many cytokine release issues, and I do think that in the future it would be safe even to do step-up in the majority of patients as an outpatient,” he said in a discussion following his presentation.
 

Durability with further follow-up

Phase 1 data for odronextamab reported by Dr. Bannerji at the 2019 ASH meeting showed encouraging safety, tolerability, and preliminary efficacy in patients with relapsed or refractory B-cell NHL at doses up to 320 mg weekly.

In the presentation at this year’s ASH meeting, Dr. Bannerji provided updated safety and efficacy results, including longer follow-up for duration of response.

In patients with relapsed/refractory FL, the overall response rate (ORR) was 90% (27 of 30 patients), including a CR rate of 70% (21 of 30 patients), it was reported at ASH 2020. The median duration of complete response (DoCR) was not reached, with 81% of CRs durable and ongoing for up to 41 months, according to Dr. Bannerji.

In patients with relapsed/refractory DLBCL who had not received prior CAR T-cell therapy, the ORR was 55% (6 of 11 patients), all of which were complete responses, data show. The median DoCR was again not reached, with 83% of CRs durable and ongoing for up to 21 months as of this report.

In a larger group of patients with relapsed/refractory DLBCL who had received CAR T-cell therapy, the ORR was 33% (8 of 24 patients) including a 21% CR rate (5 of 24 patients). Median DoCR was not reached, the study data show, with 100% of these CRs ongoing for up to 20 months.

Odronextamab was given up to 320 mg weekly with no dose-limiting toxicities and the maximum tolerated dose not reached, according to Dr. Bannerji, who noted that no patients had discontinued treatment because of CRS or neurotoxicity.

Cytokine release syndrome was seen in about 35% of patients with DLBCL, FL, or other B-cell NHLs (48 of 136 patients), and most cases were grade 1 or 2 in severity. No FL or DLBCL patients experienced CRS higher than grade 3, according to the investigator, who reported one case of grade 3 CRS occurring out of 38 FL patients (about 3%) and four cases of grade 3 CRS out of 78 total DLBCL patients (about 5%).

No patients with FL experienced immune effector cell-associated neurotoxicity syndrome (ICANS)-like events of grade 3 or greater, the investigator said. Three cases of grade 3 ICANS-like events were reported among DLBCL patients: two cases that occurred during the step-up dosing phase and one that occurred at full dose.

No TLS events of grade 3 or greater were observed in any FL or DLBCL patients, he added.
 

More research needed

Although efficacy and safety results from this phase 1 study of odronextamab are encouraging, the durability, combinability, and potential for sequencing of bispecific antibodies deserves further investigation, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

“Bispecifics in lymphoma as a class are extremely promising,” Dr. Diefenbach said in an interview. “They’re highly active and they activate an immune response against the tumor without inducing, for the most part, the same degree of neurotoxicity and CRS most CAR T cells do.

“I think the challenge is going to be to figure out how to give them in combination with other therapies to maximize durability, and how to sequence bispecifics and CAR T cells,” she added.

A global phase 2 trial of odronextamab in patients with relapsed or refractory B-cell NHL is currently recruiting. According to Dr. Bannerji, further studies are planned to evaluate odronextamab with chemotherapy and in chemotherapy-free combinations in earlier lines of treatment.

The study is sponsored by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding from Regeneron, AbbVie, F. Hoffmann La Roche Ltd/Genentech Inc., and Pharmacyclics LLC, an AbbVie company. Dr. Bannerji’s spouse is an employee of Sanofi Pasteur.
 

SOURCE: Bannerji R et al. ASH 2020, Abstract 400.

The novel bispecific antibody odronextamab (REGN1979) is demonstrating encouraging activity, durable responses, and acceptable safety in a phase 1 study of patients with highly refractory B-cell non-Hodgkin lymphoma, according to an investigator.

Durable complete responses (CRs) to odronextamab are being observed in more than 80% of heavily pretreated patients with follicular lymphoma (FL) in the ongoing study, said Rajat Bannerji, MD, PhD, of Rutgers Cancer Institute of New Jersey, New Brunswick.

Likewise, durable CRs were seen in greater than 80% of patients diffuse large B-cell lymphoma (DLBCL) not previously exposed to chimeric antigen receptor (CAR) T-cell therapy, and also in about 20% of patients who were treated with CAR T cells, Dr. Bannerji reported at the annual meeting of the American Society of Hematology, held virtually this year.

For these patients with FL or DLBCL in the phase 1 study, cytokine release syndrome (CRS) and neurotoxicity events did not exceed grade 3 in severity, and no cases of tumor lysis syndrome (TLS) were observed, Dr. Bannerji added in his presentation.

Those findings suggest odronextamab, which binds to CD3 on T cells and CD20 on malignant B cells, may offer an “off-the-shelf, primarily outpatient treatment option” for patients with relapsed or refractory B-cell NHL, he said in concluding remarks on the study.

This first-in-human study took a conservative approach, according to Dr. Bannerji, by mandating hospital admission during an initial step-up dosing schedule used along with dexamethasone to mitigate risk of CRS.

“With our step-up dosing and steroid premedication, we really have not seen too many cytokine release issues, and I do think that in the future it would be safe even to do step-up in the majority of patients as an outpatient,” he said in a discussion following his presentation.
 

Durability with further follow-up

Phase 1 data for odronextamab reported by Dr. Bannerji at the 2019 ASH meeting showed encouraging safety, tolerability, and preliminary efficacy in patients with relapsed or refractory B-cell NHL at doses up to 320 mg weekly.

In the presentation at this year’s ASH meeting, Dr. Bannerji provided updated safety and efficacy results, including longer follow-up for duration of response.

In patients with relapsed/refractory FL, the overall response rate (ORR) was 90% (27 of 30 patients), including a CR rate of 70% (21 of 30 patients), it was reported at ASH 2020. The median duration of complete response (DoCR) was not reached, with 81% of CRs durable and ongoing for up to 41 months, according to Dr. Bannerji.

In patients with relapsed/refractory DLBCL who had not received prior CAR T-cell therapy, the ORR was 55% (6 of 11 patients), all of which were complete responses, data show. The median DoCR was again not reached, with 83% of CRs durable and ongoing for up to 21 months as of this report.

In a larger group of patients with relapsed/refractory DLBCL who had received CAR T-cell therapy, the ORR was 33% (8 of 24 patients) including a 21% CR rate (5 of 24 patients). Median DoCR was not reached, the study data show, with 100% of these CRs ongoing for up to 20 months.

Odronextamab was given up to 320 mg weekly with no dose-limiting toxicities and the maximum tolerated dose not reached, according to Dr. Bannerji, who noted that no patients had discontinued treatment because of CRS or neurotoxicity.

Cytokine release syndrome was seen in about 35% of patients with DLBCL, FL, or other B-cell NHLs (48 of 136 patients), and most cases were grade 1 or 2 in severity. No FL or DLBCL patients experienced CRS higher than grade 3, according to the investigator, who reported one case of grade 3 CRS occurring out of 38 FL patients (about 3%) and four cases of grade 3 CRS out of 78 total DLBCL patients (about 5%).

No patients with FL experienced immune effector cell-associated neurotoxicity syndrome (ICANS)-like events of grade 3 or greater, the investigator said. Three cases of grade 3 ICANS-like events were reported among DLBCL patients: two cases that occurred during the step-up dosing phase and one that occurred at full dose.

No TLS events of grade 3 or greater were observed in any FL or DLBCL patients, he added.
 

More research needed

Although efficacy and safety results from this phase 1 study of odronextamab are encouraging, the durability, combinability, and potential for sequencing of bispecific antibodies deserves further investigation, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

“Bispecifics in lymphoma as a class are extremely promising,” Dr. Diefenbach said in an interview. “They’re highly active and they activate an immune response against the tumor without inducing, for the most part, the same degree of neurotoxicity and CRS most CAR T cells do.

“I think the challenge is going to be to figure out how to give them in combination with other therapies to maximize durability, and how to sequence bispecifics and CAR T cells,” she added.

A global phase 2 trial of odronextamab in patients with relapsed or refractory B-cell NHL is currently recruiting. According to Dr. Bannerji, further studies are planned to evaluate odronextamab with chemotherapy and in chemotherapy-free combinations in earlier lines of treatment.

The study is sponsored by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding from Regeneron, AbbVie, F. Hoffmann La Roche Ltd/Genentech Inc., and Pharmacyclics LLC, an AbbVie company. Dr. Bannerji’s spouse is an employee of Sanofi Pasteur.
 

SOURCE: Bannerji R et al. ASH 2020, Abstract 400.

The novel bispecific antibody odronextamab (REGN1979) is demonstrating encouraging activity, durable responses, and acceptable safety in a phase 1 study of patients with highly refractory B-cell non-Hodgkin lymphoma, according to an investigator.

Durable complete responses (CRs) to odronextamab are being observed in more than 80% of heavily pretreated patients with follicular lymphoma (FL) in the ongoing study, said Rajat Bannerji, MD, PhD, of Rutgers Cancer Institute of New Jersey, New Brunswick.

Likewise, durable CRs were seen in greater than 80% of patients diffuse large B-cell lymphoma (DLBCL) not previously exposed to chimeric antigen receptor (CAR) T-cell therapy, and also in about 20% of patients who were treated with CAR T cells, Dr. Bannerji reported at the annual meeting of the American Society of Hematology, held virtually this year.

For these patients with FL or DLBCL in the phase 1 study, cytokine release syndrome (CRS) and neurotoxicity events did not exceed grade 3 in severity, and no cases of tumor lysis syndrome (TLS) were observed, Dr. Bannerji added in his presentation.

Those findings suggest odronextamab, which binds to CD3 on T cells and CD20 on malignant B cells, may offer an “off-the-shelf, primarily outpatient treatment option” for patients with relapsed or refractory B-cell NHL, he said in concluding remarks on the study.

This first-in-human study took a conservative approach, according to Dr. Bannerji, by mandating hospital admission during an initial step-up dosing schedule used along with dexamethasone to mitigate risk of CRS.

“With our step-up dosing and steroid premedication, we really have not seen too many cytokine release issues, and I do think that in the future it would be safe even to do step-up in the majority of patients as an outpatient,” he said in a discussion following his presentation.
 

Durability with further follow-up

Phase 1 data for odronextamab reported by Dr. Bannerji at the 2019 ASH meeting showed encouraging safety, tolerability, and preliminary efficacy in patients with relapsed or refractory B-cell NHL at doses up to 320 mg weekly.

In the presentation at this year’s ASH meeting, Dr. Bannerji provided updated safety and efficacy results, including longer follow-up for duration of response.

In patients with relapsed/refractory FL, the overall response rate (ORR) was 90% (27 of 30 patients), including a CR rate of 70% (21 of 30 patients), it was reported at ASH 2020. The median duration of complete response (DoCR) was not reached, with 81% of CRs durable and ongoing for up to 41 months, according to Dr. Bannerji.

In patients with relapsed/refractory DLBCL who had not received prior CAR T-cell therapy, the ORR was 55% (6 of 11 patients), all of which were complete responses, data show. The median DoCR was again not reached, with 83% of CRs durable and ongoing for up to 21 months as of this report.

In a larger group of patients with relapsed/refractory DLBCL who had received CAR T-cell therapy, the ORR was 33% (8 of 24 patients) including a 21% CR rate (5 of 24 patients). Median DoCR was not reached, the study data show, with 100% of these CRs ongoing for up to 20 months.

Odronextamab was given up to 320 mg weekly with no dose-limiting toxicities and the maximum tolerated dose not reached, according to Dr. Bannerji, who noted that no patients had discontinued treatment because of CRS or neurotoxicity.

Cytokine release syndrome was seen in about 35% of patients with DLBCL, FL, or other B-cell NHLs (48 of 136 patients), and most cases were grade 1 or 2 in severity. No FL or DLBCL patients experienced CRS higher than grade 3, according to the investigator, who reported one case of grade 3 CRS occurring out of 38 FL patients (about 3%) and four cases of grade 3 CRS out of 78 total DLBCL patients (about 5%).

No patients with FL experienced immune effector cell-associated neurotoxicity syndrome (ICANS)-like events of grade 3 or greater, the investigator said. Three cases of grade 3 ICANS-like events were reported among DLBCL patients: two cases that occurred during the step-up dosing phase and one that occurred at full dose.

No TLS events of grade 3 or greater were observed in any FL or DLBCL patients, he added.
 

More research needed

Although efficacy and safety results from this phase 1 study of odronextamab are encouraging, the durability, combinability, and potential for sequencing of bispecific antibodies deserves further investigation, said Catherine M. Diefenbach, MD, director of the clinical lymphoma program at NYU Langone’s Perlmutter Cancer Center in New York.

“Bispecifics in lymphoma as a class are extremely promising,” Dr. Diefenbach said in an interview. “They’re highly active and they activate an immune response against the tumor without inducing, for the most part, the same degree of neurotoxicity and CRS most CAR T cells do.

“I think the challenge is going to be to figure out how to give them in combination with other therapies to maximize durability, and how to sequence bispecifics and CAR T cells,” she added.

A global phase 2 trial of odronextamab in patients with relapsed or refractory B-cell NHL is currently recruiting. According to Dr. Bannerji, further studies are planned to evaluate odronextamab with chemotherapy and in chemotherapy-free combinations in earlier lines of treatment.

The study is sponsored by Regeneron Pharmaceuticals. Dr. Bannerji reported research funding from Regeneron, AbbVie, F. Hoffmann La Roche Ltd/Genentech Inc., and Pharmacyclics LLC, an AbbVie company. Dr. Bannerji’s spouse is an employee of Sanofi Pasteur.
 

SOURCE: Bannerji R et al. ASH 2020, Abstract 400.

Pfizer won’t be able to provide more COVID-19 vaccine doses to the United States until late June or July because other countries have bought up the available supply, according to The Washington Post.

The U.S. government signed a deal with the giant pharmaceutical company earlier this year to provide 100 million doses for $1.95 billion – enough for 50 million Americans to receive the two-dose vaccine. At that time, Pfizer officials encouraged Operation Warp Speed officials to purchase an additional 100 million doses, The New York Times first reported Dec. 7, but the federal officials declined.

Since then, other countries have signed vaccine deals with Pfizer, so the U.S. may not be able to receive a second major allotment until the summer of 2021, The Washington Post reported. Without a substantial number of additional doses, the U.S. may not be able to follow its schedule of vaccinating the majority of Americans against COVID-19 by April or May.

However, Trump administration officials told the newspaper that there won’t be issues, citing other vaccine companies such as Moderna.

“I’m not concerned about our ability to buy vaccines to offer to all of the American public,” Gen. Paul Ostrowski, who oversees logistics for Operation Warp Speed, told The Washington Post.

“It’s clear that Pfizer made plans with other countries. Many have been announced. We understand those pieces,” he said.

With Pfizer’s COVID-19 vaccine on the verge of FDA approval, federal officials contacted the company last weekend to buy another 100 million doses, but the company said its current supply is already committed, the newspaper reported.

The vaccine from Pfizer and BioNTech is expected to win emergency approval within days and has been shown to be effective against COVID-19.

Pfizer added that it may be able to provide 50 million doses at the end of the second quarter and another 50 million doses during the third quarter. However, the company can’t offer anything “substantial” until next summer.

Beyond the initial 100 million doses that the U.S. has already secured, Pfizer and federal officials would need to negotiate a new, “separate and mutually acceptable agreement,” Amy Rose, a spokeswoman for Pfizer, told the newspaper.

On Dec. 8, President Donald Trump was expected to sign an executive order prioritizing vaccination for Americans first before providing doses to other countries, according to Fox News.

The order will provide guidelines to the Department of Health and Human Services, the U.S. Agency for International Development and the U.S. International Development Finance Corporation for foreign assistance with vaccines, the news outlet reported.

It’s unclear whether the executive order is related to the Pfizer issue, whether the president can prevent a private company from fulfilling contracts with other countries, and whether President-elect Joe Biden will create his own policy, according to CNBC. The order may prove to be mostly symbolic.

The FDA could issue an emergency use authorization for Pfizer’s coronavirus vaccine this week and will likely approve Moderna’s vaccine next week. The U.S. has signed a contract with Moderna for 100 million doses.

During a call with reporters on Dec. 7, a spokeswoman for the Department of Health and Human Services said, “We are confident that we will have 100 million doses of Pfizer’s vaccine as agreed to in our contract, and beyond that, we have five other vaccine candidates, including 100 million doses on the way from Moderna.”

Federal officials are counting on vaccine candidates from AstraZeneca and Johnson & Johnson to seek FDA approval in January and be ready for shipment in February.

“We could have all of them,” Moncef Slaoui, the chief science adviser for Operation Warp Speed, told The Washington Post on Dec. 7.

“And for this reason, we feel confident we could cover the needs without a specific cliff,” he said. “We have planned things in such a way as we would indeed avoid a cliff.”

This article first appeared on WebMD.com.

Pfizer won’t be able to provide more COVID-19 vaccine doses to the United States until late June or July because other countries have bought up the available supply, according to The Washington Post.

The U.S. government signed a deal with the giant pharmaceutical company earlier this year to provide 100 million doses for $1.95 billion – enough for 50 million Americans to receive the two-dose vaccine. At that time, Pfizer officials encouraged Operation Warp Speed officials to purchase an additional 100 million doses, The New York Times first reported Dec. 7, but the federal officials declined.

Since then, other countries have signed vaccine deals with Pfizer, so the U.S. may not be able to receive a second major allotment until the summer of 2021, The Washington Post reported. Without a substantial number of additional doses, the U.S. may not be able to follow its schedule of vaccinating the majority of Americans against COVID-19 by April or May.

However, Trump administration officials told the newspaper that there won’t be issues, citing other vaccine companies such as Moderna.

“I’m not concerned about our ability to buy vaccines to offer to all of the American public,” Gen. Paul Ostrowski, who oversees logistics for Operation Warp Speed, told The Washington Post.

“It’s clear that Pfizer made plans with other countries. Many have been announced. We understand those pieces,” he said.

With Pfizer’s COVID-19 vaccine on the verge of FDA approval, federal officials contacted the company last weekend to buy another 100 million doses, but the company said its current supply is already committed, the newspaper reported.

The vaccine from Pfizer and BioNTech is expected to win emergency approval within days and has been shown to be effective against COVID-19.

Pfizer added that it may be able to provide 50 million doses at the end of the second quarter and another 50 million doses during the third quarter. However, the company can’t offer anything “substantial” until next summer.

Beyond the initial 100 million doses that the U.S. has already secured, Pfizer and federal officials would need to negotiate a new, “separate and mutually acceptable agreement,” Amy Rose, a spokeswoman for Pfizer, told the newspaper.

On Dec. 8, President Donald Trump was expected to sign an executive order prioritizing vaccination for Americans first before providing doses to other countries, according to Fox News.

The order will provide guidelines to the Department of Health and Human Services, the U.S. Agency for International Development and the U.S. International Development Finance Corporation for foreign assistance with vaccines, the news outlet reported.

It’s unclear whether the executive order is related to the Pfizer issue, whether the president can prevent a private company from fulfilling contracts with other countries, and whether President-elect Joe Biden will create his own policy, according to CNBC. The order may prove to be mostly symbolic.

The FDA could issue an emergency use authorization for Pfizer’s coronavirus vaccine this week and will likely approve Moderna’s vaccine next week. The U.S. has signed a contract with Moderna for 100 million doses.

During a call with reporters on Dec. 7, a spokeswoman for the Department of Health and Human Services said, “We are confident that we will have 100 million doses of Pfizer’s vaccine as agreed to in our contract, and beyond that, we have five other vaccine candidates, including 100 million doses on the way from Moderna.”

Federal officials are counting on vaccine candidates from AstraZeneca and Johnson & Johnson to seek FDA approval in January and be ready for shipment in February.

“We could have all of them,” Moncef Slaoui, the chief science adviser for Operation Warp Speed, told The Washington Post on Dec. 7.

“And for this reason, we feel confident we could cover the needs without a specific cliff,” he said. “We have planned things in such a way as we would indeed avoid a cliff.”

This article first appeared on WebMD.com.

Pfizer won’t be able to provide more COVID-19 vaccine doses to the United States until late June or July because other countries have bought up the available supply, according to The Washington Post.

The U.S. government signed a deal with the giant pharmaceutical company earlier this year to provide 100 million doses for $1.95 billion – enough for 50 million Americans to receive the two-dose vaccine. At that time, Pfizer officials encouraged Operation Warp Speed officials to purchase an additional 100 million doses, The New York Times first reported Dec. 7, but the federal officials declined.

Since then, other countries have signed vaccine deals with Pfizer, so the U.S. may not be able to receive a second major allotment until the summer of 2021, The Washington Post reported. Without a substantial number of additional doses, the U.S. may not be able to follow its schedule of vaccinating the majority of Americans against COVID-19 by April or May.

However, Trump administration officials told the newspaper that there won’t be issues, citing other vaccine companies such as Moderna.

“I’m not concerned about our ability to buy vaccines to offer to all of the American public,” Gen. Paul Ostrowski, who oversees logistics for Operation Warp Speed, told The Washington Post.

“It’s clear that Pfizer made plans with other countries. Many have been announced. We understand those pieces,” he said.

With Pfizer’s COVID-19 vaccine on the verge of FDA approval, federal officials contacted the company last weekend to buy another 100 million doses, but the company said its current supply is already committed, the newspaper reported.

The vaccine from Pfizer and BioNTech is expected to win emergency approval within days and has been shown to be effective against COVID-19.

Pfizer added that it may be able to provide 50 million doses at the end of the second quarter and another 50 million doses during the third quarter. However, the company can’t offer anything “substantial” until next summer.

Beyond the initial 100 million doses that the U.S. has already secured, Pfizer and federal officials would need to negotiate a new, “separate and mutually acceptable agreement,” Amy Rose, a spokeswoman for Pfizer, told the newspaper.

On Dec. 8, President Donald Trump was expected to sign an executive order prioritizing vaccination for Americans first before providing doses to other countries, according to Fox News.

The order will provide guidelines to the Department of Health and Human Services, the U.S. Agency for International Development and the U.S. International Development Finance Corporation for foreign assistance with vaccines, the news outlet reported.

It’s unclear whether the executive order is related to the Pfizer issue, whether the president can prevent a private company from fulfilling contracts with other countries, and whether President-elect Joe Biden will create his own policy, according to CNBC. The order may prove to be mostly symbolic.

The FDA could issue an emergency use authorization for Pfizer’s coronavirus vaccine this week and will likely approve Moderna’s vaccine next week. The U.S. has signed a contract with Moderna for 100 million doses.

During a call with reporters on Dec. 7, a spokeswoman for the Department of Health and Human Services said, “We are confident that we will have 100 million doses of Pfizer’s vaccine as agreed to in our contract, and beyond that, we have five other vaccine candidates, including 100 million doses on the way from Moderna.”

Federal officials are counting on vaccine candidates from AstraZeneca and Johnson & Johnson to seek FDA approval in January and be ready for shipment in February.

“We could have all of them,” Moncef Slaoui, the chief science adviser for Operation Warp Speed, told The Washington Post on Dec. 7.

“And for this reason, we feel confident we could cover the needs without a specific cliff,” he said. “We have planned things in such a way as we would indeed avoid a cliff.”

This article first appeared on WebMD.com.

As hospitals across the country develop their plans to vaccinate their health care employees against COVID-19, a key question has come to the fore: What if an employee – whether nurse, physician, or other health care worker – refuses to receive the vaccine? Can hospitals require their employees to be vaccinated against COVID-19? And what consequences could an employee face for refusing the vaccine?

My answer needs to be based, in part, on the law related to previous vaccines – influenza, for example – because at the time of this writing (early December 2020), no vaccine for COVID-19 has been approved, although approval of at least one vaccine is expected within a week. So there have been no offers of vaccine and refusals yet, nor are there any cases to date involving an employee who refused a COVID-19 vaccine. As of December 2020, there are no state or federal laws that either require an employee to be vaccinated against COVID-19 or that protect an employee who refuses vaccination against COVID-19. It will take a while after the vaccine is approved and distributed before refusals, reactions, policies, cases, and laws begin to emerge.

If we look at the law related to health care workers refusing to be vaccinated against the closest relative to COVID-19 – influenza – then the answer would be yes, employers can require employees to be vaccinated.

An employer can fire an employee who refuses influenza vaccination. If an employee who refused and was fired sues the employer for wrongful termination, the employee has more or less chance of success depending on the reason for refusal. Some courts and the Equal Employment Opportunity Commission have held that a refusal on religious grounds is protected by the U.S. Constitution, as in this recent case. The Constitution protects freedom to practice one’s religion. Specific religions may have a range of tenets that support refusal to be vaccinated.

A refusal on medical grounds has been successful if the medical grounds fall under the protections of the Americans with Disabilities Act but may fail when the medical grounds for the claim are not covered by the ADA.

Refusal for secular, nonmedical reasons, such as a health care worker’s policy of treating their body as their temple, has not gone over well with employers or courts. However, in at least one case, a nurse who refused vaccination on secular, nonmedical grounds won her case against her employer, on appeal. The appeals court found that the hospital violated her First Amendment rights.

Employees who refuse vaccination for religious or medical reasons still will need to take measures to protect patients and other employees from infection. An employer such as a hospital can, rather than fire the employee, offer the employee an accommodation, such as requiring that the employee wear a mask or quarantine. There are no cases that have upheld an employee’s right to refuse to wear a mask or quarantine.

The situation with the COVID-19 vaccine is different from the situation surrounding influenza vaccines. There are plenty of data on effectiveness and side effects of influenza vaccines, but there is very little evidence of short- or long-term effects of the COVID-19 vaccines currently being tested and/or considered for approval. One could argue that the process of vaccine development is the same for all virus vaccines. However, public confidence in the vaccine vetting process is not what it once was. It has been widely publicized that the COVID-19 vaccine trials have been rushed. As of December 2020, only 60% of the general population say they would take the vaccine, although researchers say confidence is increasing.

The Centers for Disease Control and Prevention has designated health care workers as first in line to get the vaccine, but some health care workers may not want to be the first to try it. A CDC survey found that 63% of health care workers polled in recent months said they would get a COVID-19 vaccine.

Unions have entered the conversation. A coalition of unions that represent health care workers said, “we need a transparent, evidence-based federal vaccine strategy based on principles of equity, safety, and priority, as well as robust efforts to address a high degree of skepticism about safety of an authorized vaccine.” The organization declined to promote a vaccine until more is known.

As of publication date, the EEOC guidance for employers responding to COVID-19 does not address vaccines.

The CDC’s Interim Guidance for Businesses and Employers Responding to Coronavirus Disease 2019, May 2020, updated Dec. 4, 2020, does not address vaccines. The CDC’s page on COVID-19 vaccination for health care workers does not address a health care worker’s refusal. The site does assure health care workers that the vaccine development process is sound: “The current vaccine safety system is strong and robust, with the capacity to effectively monitor COVID-19 vaccine safety. Existing data systems have validated analytic methods that can rapidly detect statistical signals for possible vaccine safety problems. These systems are being scaled up to fully meet the needs of the nation. Additional systems and data sources are also being developed to further enhance safety monitoring capabilities. CDC is committed to ensuring that COVID-19 vaccines are safe.”

In the coming months, government officials and vaccine manufacturers will be working to reassure the public of the safety of the vaccine and the rigor of the vaccine development process. In November 2020, National Institute of Allergy and Infectious Diseases Director Anthony Fauci, MD, told Kaiser Health News: “The company looks at the data. I look at the data. Then the company puts the data to the FDA. The FDA will make the decision to do an emergency-use authorization or a license application approval. And they have career scientists who are really independent. They’re not beholden to anybody. Then there’s another independent group, the Vaccines and Related Biological Products Advisory Committee. The FDA commissioner has vowed publicly that he will go according to the opinion of the career scientists and the advisory board.” President-elect Joe Biden said he would get a vaccine when Dr. Fauci thinks it is safe.

An employee who, after researching the vaccine and the process, still wants to refuse when offered the vaccine is not likely to be fired for that reason right away, as long as the employee takes other precautions, such as wearing a mask. If the employer does fire the employee and the employee sues the employer, it is impossible to predict how a court would decide the case.

Related legal questions may arise in the coming months. For example:

• Is an employer exempt from paying workers’ compensation to an employee who refuses to be vaccinated and then contracts the virus while on the job?
• Can a prospective employer require COVID-19 vaccination as a precondition of employment?
• Is it within a patient’s rights to receive an answer to the question: Has my health care worker been vaccinated against COVID-19?
• If a hospital allows employees to refuse vaccination and keep working, and an outbreak occurs, and it is suggested through contact tracing that unvaccinated workers infected patients, will a court hold the hospital liable for patients’ damages?

Answers to these questions are yet to be determined.

Carolyn Buppert (www.buppert.com) is an attorney and former nurse practitioner who focuses on the legal issues affecting nurse practitioners.

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

As hospitals across the country develop their plans to vaccinate their health care employees against COVID-19, a key question has come to the fore: What if an employee – whether nurse, physician, or other health care worker – refuses to receive the vaccine? Can hospitals require their employees to be vaccinated against COVID-19? And what consequences could an employee face for refusing the vaccine?

My answer needs to be based, in part, on the law related to previous vaccines – influenza, for example – because at the time of this writing (early December 2020), no vaccine for COVID-19 has been approved, although approval of at least one vaccine is expected within a week. So there have been no offers of vaccine and refusals yet, nor are there any cases to date involving an employee who refused a COVID-19 vaccine. As of December 2020, there are no state or federal laws that either require an employee to be vaccinated against COVID-19 or that protect an employee who refuses vaccination against COVID-19. It will take a while after the vaccine is approved and distributed before refusals, reactions, policies, cases, and laws begin to emerge.

If we look at the law related to health care workers refusing to be vaccinated against the closest relative to COVID-19 – influenza – then the answer would be yes, employers can require employees to be vaccinated.

An employer can fire an employee who refuses influenza vaccination. If an employee who refused and was fired sues the employer for wrongful termination, the employee has more or less chance of success depending on the reason for refusal. Some courts and the Equal Employment Opportunity Commission have held that a refusal on religious grounds is protected by the U.S. Constitution, as in this recent case. The Constitution protects freedom to practice one’s religion. Specific religions may have a range of tenets that support refusal to be vaccinated.

A refusal on medical grounds has been successful if the medical grounds fall under the protections of the Americans with Disabilities Act but may fail when the medical grounds for the claim are not covered by the ADA.

Refusal for secular, nonmedical reasons, such as a health care worker’s policy of treating their body as their temple, has not gone over well with employers or courts. However, in at least one case, a nurse who refused vaccination on secular, nonmedical grounds won her case against her employer, on appeal. The appeals court found that the hospital violated her First Amendment rights.

Employees who refuse vaccination for religious or medical reasons still will need to take measures to protect patients and other employees from infection. An employer such as a hospital can, rather than fire the employee, offer the employee an accommodation, such as requiring that the employee wear a mask or quarantine. There are no cases that have upheld an employee’s right to refuse to wear a mask or quarantine.

The situation with the COVID-19 vaccine is different from the situation surrounding influenza vaccines. There are plenty of data on effectiveness and side effects of influenza vaccines, but there is very little evidence of short- or long-term effects of the COVID-19 vaccines currently being tested and/or considered for approval. One could argue that the process of vaccine development is the same for all virus vaccines. However, public confidence in the vaccine vetting process is not what it once was. It has been widely publicized that the COVID-19 vaccine trials have been rushed. As of December 2020, only 60% of the general population say they would take the vaccine, although researchers say confidence is increasing.

The Centers for Disease Control and Prevention has designated health care workers as first in line to get the vaccine, but some health care workers may not want to be the first to try it. A CDC survey found that 63% of health care workers polled in recent months said they would get a COVID-19 vaccine.

Unions have entered the conversation. A coalition of unions that represent health care workers said, “we need a transparent, evidence-based federal vaccine strategy based on principles of equity, safety, and priority, as well as robust efforts to address a high degree of skepticism about safety of an authorized vaccine.” The organization declined to promote a vaccine until more is known.

As of publication date, the EEOC guidance for employers responding to COVID-19 does not address vaccines.

The CDC’s Interim Guidance for Businesses and Employers Responding to Coronavirus Disease 2019, May 2020, updated Dec. 4, 2020, does not address vaccines. The CDC’s page on COVID-19 vaccination for health care workers does not address a health care worker’s refusal. The site does assure health care workers that the vaccine development process is sound: “The current vaccine safety system is strong and robust, with the capacity to effectively monitor COVID-19 vaccine safety. Existing data systems have validated analytic methods that can rapidly detect statistical signals for possible vaccine safety problems. These systems are being scaled up to fully meet the needs of the nation. Additional systems and data sources are also being developed to further enhance safety monitoring capabilities. CDC is committed to ensuring that COVID-19 vaccines are safe.”

In the coming months, government officials and vaccine manufacturers will be working to reassure the public of the safety of the vaccine and the rigor of the vaccine development process. In November 2020, National Institute of Allergy and Infectious Diseases Director Anthony Fauci, MD, told Kaiser Health News: “The company looks at the data. I look at the data. Then the company puts the data to the FDA. The FDA will make the decision to do an emergency-use authorization or a license application approval. And they have career scientists who are really independent. They’re not beholden to anybody. Then there’s another independent group, the Vaccines and Related Biological Products Advisory Committee. The FDA commissioner has vowed publicly that he will go according to the opinion of the career scientists and the advisory board.” President-elect Joe Biden said he would get a vaccine when Dr. Fauci thinks it is safe.

An employee who, after researching the vaccine and the process, still wants to refuse when offered the vaccine is not likely to be fired for that reason right away, as long as the employee takes other precautions, such as wearing a mask. If the employer does fire the employee and the employee sues the employer, it is impossible to predict how a court would decide the case.

Related legal questions may arise in the coming months. For example:

• Is an employer exempt from paying workers’ compensation to an employee who refuses to be vaccinated and then contracts the virus while on the job?
• Can a prospective employer require COVID-19 vaccination as a precondition of employment?
• Is it within a patient’s rights to receive an answer to the question: Has my health care worker been vaccinated against COVID-19?
• If a hospital allows employees to refuse vaccination and keep working, and an outbreak occurs, and it is suggested through contact tracing that unvaccinated workers infected patients, will a court hold the hospital liable for patients’ damages?

Answers to these questions are yet to be determined.

Carolyn Buppert (www.buppert.com) is an attorney and former nurse practitioner who focuses on the legal issues affecting nurse practitioners.

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

As hospitals across the country develop their plans to vaccinate their health care employees against COVID-19, a key question has come to the fore: What if an employee – whether nurse, physician, or other health care worker – refuses to receive the vaccine? Can hospitals require their employees to be vaccinated against COVID-19? And what consequences could an employee face for refusing the vaccine?

My answer needs to be based, in part, on the law related to previous vaccines – influenza, for example – because at the time of this writing (early December 2020), no vaccine for COVID-19 has been approved, although approval of at least one vaccine is expected within a week. So there have been no offers of vaccine and refusals yet, nor are there any cases to date involving an employee who refused a COVID-19 vaccine. As of December 2020, there are no state or federal laws that either require an employee to be vaccinated against COVID-19 or that protect an employee who refuses vaccination against COVID-19. It will take a while after the vaccine is approved and distributed before refusals, reactions, policies, cases, and laws begin to emerge.

If we look at the law related to health care workers refusing to be vaccinated against the closest relative to COVID-19 – influenza – then the answer would be yes, employers can require employees to be vaccinated.

An employer can fire an employee who refuses influenza vaccination. If an employee who refused and was fired sues the employer for wrongful termination, the employee has more or less chance of success depending on the reason for refusal. Some courts and the Equal Employment Opportunity Commission have held that a refusal on religious grounds is protected by the U.S. Constitution, as in this recent case. The Constitution protects freedom to practice one’s religion. Specific religions may have a range of tenets that support refusal to be vaccinated.

A refusal on medical grounds has been successful if the medical grounds fall under the protections of the Americans with Disabilities Act but may fail when the medical grounds for the claim are not covered by the ADA.

Refusal for secular, nonmedical reasons, such as a health care worker’s policy of treating their body as their temple, has not gone over well with employers or courts. However, in at least one case, a nurse who refused vaccination on secular, nonmedical grounds won her case against her employer, on appeal. The appeals court found that the hospital violated her First Amendment rights.

Employees who refuse vaccination for religious or medical reasons still will need to take measures to protect patients and other employees from infection. An employer such as a hospital can, rather than fire the employee, offer the employee an accommodation, such as requiring that the employee wear a mask or quarantine. There are no cases that have upheld an employee’s right to refuse to wear a mask or quarantine.

The situation with the COVID-19 vaccine is different from the situation surrounding influenza vaccines. There are plenty of data on effectiveness and side effects of influenza vaccines, but there is very little evidence of short- or long-term effects of the COVID-19 vaccines currently being tested and/or considered for approval. One could argue that the process of vaccine development is the same for all virus vaccines. However, public confidence in the vaccine vetting process is not what it once was. It has been widely publicized that the COVID-19 vaccine trials have been rushed. As of December 2020, only 60% of the general population say they would take the vaccine, although researchers say confidence is increasing.

The Centers for Disease Control and Prevention has designated health care workers as first in line to get the vaccine, but some health care workers may not want to be the first to try it. A CDC survey found that 63% of health care workers polled in recent months said they would get a COVID-19 vaccine.

Unions have entered the conversation. A coalition of unions that represent health care workers said, “we need a transparent, evidence-based federal vaccine strategy based on principles of equity, safety, and priority, as well as robust efforts to address a high degree of skepticism about safety of an authorized vaccine.” The organization declined to promote a vaccine until more is known.

As of publication date, the EEOC guidance for employers responding to COVID-19 does not address vaccines.

The CDC’s Interim Guidance for Businesses and Employers Responding to Coronavirus Disease 2019, May 2020, updated Dec. 4, 2020, does not address vaccines. The CDC’s page on COVID-19 vaccination for health care workers does not address a health care worker’s refusal. The site does assure health care workers that the vaccine development process is sound: “The current vaccine safety system is strong and robust, with the capacity to effectively monitor COVID-19 vaccine safety. Existing data systems have validated analytic methods that can rapidly detect statistical signals for possible vaccine safety problems. These systems are being scaled up to fully meet the needs of the nation. Additional systems and data sources are also being developed to further enhance safety monitoring capabilities. CDC is committed to ensuring that COVID-19 vaccines are safe.”

In the coming months, government officials and vaccine manufacturers will be working to reassure the public of the safety of the vaccine and the rigor of the vaccine development process. In November 2020, National Institute of Allergy and Infectious Diseases Director Anthony Fauci, MD, told Kaiser Health News: “The company looks at the data. I look at the data. Then the company puts the data to the FDA. The FDA will make the decision to do an emergency-use authorization or a license application approval. And they have career scientists who are really independent. They’re not beholden to anybody. Then there’s another independent group, the Vaccines and Related Biological Products Advisory Committee. The FDA commissioner has vowed publicly that he will go according to the opinion of the career scientists and the advisory board.” President-elect Joe Biden said he would get a vaccine when Dr. Fauci thinks it is safe.

An employee who, after researching the vaccine and the process, still wants to refuse when offered the vaccine is not likely to be fired for that reason right away, as long as the employee takes other precautions, such as wearing a mask. If the employer does fire the employee and the employee sues the employer, it is impossible to predict how a court would decide the case.

Related legal questions may arise in the coming months. For example:

• Is an employer exempt from paying workers’ compensation to an employee who refuses to be vaccinated and then contracts the virus while on the job?
• Can a prospective employer require COVID-19 vaccination as a precondition of employment?
• Is it within a patient’s rights to receive an answer to the question: Has my health care worker been vaccinated against COVID-19?
• If a hospital allows employees to refuse vaccination and keep working, and an outbreak occurs, and it is suggested through contact tracing that unvaccinated workers infected patients, will a court hold the hospital liable for patients’ damages?

Answers to these questions are yet to be determined.

Carolyn Buppert (www.buppert.com) is an attorney and former nurse practitioner who focuses on the legal issues affecting nurse practitioners.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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

Patients who are profoundly immunosuppressed after extensive cancer treatment, and who fall ill with COVID-19, can shed viable SARS-CoV-2 virus for at least 2 months after symptom onset and may need extended periods of isolation.

Live-virus shedding was detected in 18 patients who had undergone hematopoietic stem cell transplants or chimeric antigen receptor (CAR) T-cell therapy and in 2 patients with lymphoma. 

The finding was reported Dec. 1 in a research letter in the New England Journal of Medicine. 

Individuals who are otherwise healthy when they get COVID-19 are “no longer infectious after the first week of illness,” said lead author Mini Kamboj, MD, chief medical epidemiologist, Memorial Sloan Kettering Cancer Center, New York. 

“We need to keep an open mind about how [much] longer immunocompromised patients could pose an infection risk to others,” she added.

Dr. Kamboj said in an interview that her team’s previous experience with stem cell transplant recipients had suggested that severely immunocompromised patients shed other viruses (such as respiratory syncytial virus, parainfluenza, and influenza) for longer periods of time than do healthy controls.

Based on their latest findings, the investigators suggest that current guidelines for COVID-19 isolation precautions may need to be revised for immunocompromised patients. Even if only a small proportion of patients with cancer who have COVID-19 remain contagious for prolonged periods of time, “it’s a residual risk that we need to address,” Dr. Kamboj said. 

Dr. Kamboj also suggested that physicians follow test-based criteria to determine when a patient undergoing transplant can be released from isolation.
 

Shedding of viable virus

For this study, the investigators used cell cultures to detect viable virus in serially collected nasopharyngeal and sputum samples from 20 immunocompromised patients who had COVID-19 (diagnosed with COVID-19 between March 10 and April 20).  

Patients had lymphoma (n = 8), multiple myeloma (n= 7), acute leukemia/myelodysplastic syndrome (n = 4), and chronic leukemia (n = 1). There were 16 patients who had undergone transplant, 2 who had received CAR T-cell therapy, and 2 who had received other therapy.

There were 15 patients receiving active treatment or chemotherapy, and 11 developed severe COVID-19 infection. 

In total, 78 respiratory samples were collected.

“Viral RNA was detected for up to 78 days after the onset of symptoms,” the researchers reported, “[and] viable virus was detected in 10 of 14 nasopharyngeal samples (71%) that were available from the first day of laboratory testing.”

Five patients were followed up, and from these patients, the team grew virus in culture for up to 61 days after symptom onset. Two among this small group of five patients had received allogenic hematopoietic stem cell transplantation and one patient had been treated with CAR T-cell therapy within the previous 6 months. This patient remained seronegative for antibodies to the coronavirus.

For 11 patients, the team obtained serial sample genomes and found that  “each patient was infected by a distinct virus and there were no major changes in the consensus sequences of the original serial specimens or cultured isolates.” These findings were consistent with persistent infection, they noted.

The authors have disclosed no relevant financial relationships.

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