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FDA approves new immunotherapy combo for metastatic melanoma
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
in adults and children 12 years or older, according to the drug’s manufacturer, Bristol-Myers Squibb.
Approval was based on the company’s RELATIVITY-047 trial, which found a median progression-free survival (PFS) of 10.1 months among 355 patients randomly assigned to the combination therapy compared with 4.6 months among 359 patients who received nivolumab alone (hazard ratio, 0.75; P = .0055).
In the combination therapy group, 18.9% of patients reported a grade 3/4 drug-related adverse event, compared with 9.7% in the nivolumab group; 14.6% of patients in the combination group had drug-related adverse events leading to discontinuation versus 6.7% of those receiving monotherapy, the company noted in a press release.
Relatlimab is the company’s third immune checkpoint inhibitor to reach the U.S. market, joining the PD-1 inhibitor nivolumab and the CTLA-4 blocker ipilimumab. Relatlimab targets LAG-3, a cell-surface receptor found on activated CD4+ T cells.
Nivolumab plus ipilimumab is currently the standard of care for previously untreated metastatic or inoperable melanoma. Both combinations produce similar PFS, but the incidence of grade 3/4 adverse events is higher with ipilimumab, according to a Jan. 6, 2022, editorial in the New England Journal of Medicine.
Musculoskeletal pain, fatigue, rash, pruritus, and diarrhea were the most common adverse reactions with combination nivolumab/relatlimab, occurring in 20% or more of RELATIVITY-047 trial participants.
Adrenal insufficiency, anemia, colitis, pneumonia, and myocardial infarction were the most frequent serious adverse reactions, but each occurred in less than 2% of patients. There were three fatal adverse events in the trial caused by hemophagocytic lymphohistiocytosis, acute lung edema, and pneumonitis.
The approved dosage is 480 mg nivolumab and 160 mg relatlimab administered intravenously every 4 weeks.
A version of this article first appeared on Medscape.com.
FDA approves upadacitinib for ulcerative colitis
The Food and Drug Administration has approved upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who do not respond adequately to or can’t tolerate anti–tumor necrosis factor (TNF) agents.
It marks the first FDA approval for the selective Janus kinase (JAK) inhibitor in gastroenterology and is supported by efficacy and safety data from three phase 3 randomized, double-blind, placebo-controlled clinical studies.
In clinical trials, upadacitinib achieved the primary endpoints of clinical remission, per modified Mayo Score, at 8 and 52 weeks.
In addition, a greater proportion of patients who received upadacitinib achieved clinical response as early as the second week of treatment and steroid-free clinical remission at 1 year, as well as key endoscopic and histologic improvement endpoints at 8 and 52 weeks.
“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” Maria T. Abreu, MD, director, Crohn’s and Colitis Center, University of Miami Health System, said in a news release issued by AbbVie.
Upadacitinib has been shown to “rapidly control symptoms,” said Dr. Abreu, adding, “I believe these types of improvements can make a positive difference for my patients.”
Upadacitinib is also approved in the United States to treat adults with moderate to severe rheumatoid arthritis, moderate to severe atopic dermatitis, and active psoriatic arthritis.
Overall, the safety profile observed in patients with UC who were treated with upadacitinib was generally similar to the safety profile in patients with rheumatoid arthritis and atopic dermatitis.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who do not respond adequately to or can’t tolerate anti–tumor necrosis factor (TNF) agents.
It marks the first FDA approval for the selective Janus kinase (JAK) inhibitor in gastroenterology and is supported by efficacy and safety data from three phase 3 randomized, double-blind, placebo-controlled clinical studies.
In clinical trials, upadacitinib achieved the primary endpoints of clinical remission, per modified Mayo Score, at 8 and 52 weeks.
In addition, a greater proportion of patients who received upadacitinib achieved clinical response as early as the second week of treatment and steroid-free clinical remission at 1 year, as well as key endoscopic and histologic improvement endpoints at 8 and 52 weeks.
“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” Maria T. Abreu, MD, director, Crohn’s and Colitis Center, University of Miami Health System, said in a news release issued by AbbVie.
Upadacitinib has been shown to “rapidly control symptoms,” said Dr. Abreu, adding, “I believe these types of improvements can make a positive difference for my patients.”
Upadacitinib is also approved in the United States to treat adults with moderate to severe rheumatoid arthritis, moderate to severe atopic dermatitis, and active psoriatic arthritis.
Overall, the safety profile observed in patients with UC who were treated with upadacitinib was generally similar to the safety profile in patients with rheumatoid arthritis and atopic dermatitis.
A version of this article first appeared on Medscape.com.
The Food and Drug Administration has approved upadacitinib (Rinvoq) for the treatment of adults with moderately to severely active ulcerative colitis (UC) who do not respond adequately to or can’t tolerate anti–tumor necrosis factor (TNF) agents.
It marks the first FDA approval for the selective Janus kinase (JAK) inhibitor in gastroenterology and is supported by efficacy and safety data from three phase 3 randomized, double-blind, placebo-controlled clinical studies.
In clinical trials, upadacitinib achieved the primary endpoints of clinical remission, per modified Mayo Score, at 8 and 52 weeks.
In addition, a greater proportion of patients who received upadacitinib achieved clinical response as early as the second week of treatment and steroid-free clinical remission at 1 year, as well as key endoscopic and histologic improvement endpoints at 8 and 52 weeks.
“Ulcerative colitis patients live with unpredictable symptoms such as increased stool frequency and bleeding, which can make daily activities difficult,” Maria T. Abreu, MD, director, Crohn’s and Colitis Center, University of Miami Health System, said in a news release issued by AbbVie.
Upadacitinib has been shown to “rapidly control symptoms,” said Dr. Abreu, adding, “I believe these types of improvements can make a positive difference for my patients.”
Upadacitinib is also approved in the United States to treat adults with moderate to severe rheumatoid arthritis, moderate to severe atopic dermatitis, and active psoriatic arthritis.
Overall, the safety profile observed in patients with UC who were treated with upadacitinib was generally similar to the safety profile in patients with rheumatoid arthritis and atopic dermatitis.
A version of this article first appeared on Medscape.com.
FDA clears once-weekly transdermal patch for Alzheimer’s
Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.
Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.
“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.
“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.
The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.
The company expects the donepezil transdermal patch to be available in early Fall 2022.
A version of this article first appeared on Medscape.com.
Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.
Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.
“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.
“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.
The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.
The company expects the donepezil transdermal patch to be available in early Fall 2022.
A version of this article first appeared on Medscape.com.
Adlarity is the first and only once-weekly patch to continuously deliver consistent doses of the acetylcholinesterase inhibitor through the skin, bypassing the digestive system and resulting in low likelihood of gastrointestinal side effects associated with oral donepezil, the company said in a press release.
Each patch delivers either 5 mg or 10 mg of donepezil daily for 7 days. After that, it is removed and a new patch is applied.
“The availability of a once-weekly patch formulation of donepezil has the potential to substantially benefit patients, caregivers, and health care providers,” Pierre Tariot, MD, director of the Banner Alzheimer’s Institute, Phoenix, said in the release.
“It offers effective, well-tolerated, and stable dosing for 7 days for patients who cannot take daily oral donepezil reliably because of impaired memory. It can also offer benefits for those patients who have diminished ability to swallow or have GI side effects associated with ingestion of oral donepezil,” Dr. Tariot added.
The FDA approved Adlarity through the 505(b)(2) regulatory pathway, which allows the agency to refer to previous findings of safety and efficacy for an already-approved product, as well as to review findings from further studies of the product.
The company expects the donepezil transdermal patch to be available in early Fall 2022.
A version of this article first appeared on Medscape.com.
FDA approves first PARP inhibitor for early BRCA+ breast cancer
BRCA+ breast cancer
Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.
The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.
The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.
The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.
Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.
The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.
A version of this article first appeared on Medscape.com.
Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.
The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.
The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.
The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.
Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.
The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.
A version of this article first appeared on Medscape.com.
Specifically, the new approval is for the adjuvant treatment of adult patients with high-risk early-stage HER2-negative, BRCA-mutated breast cancer who have completed chemotherapy and local treatment.
The FDA also approved BRACAnalysis CDx (Myriad Genetics), a companion diagnostic test to identify patients who may benefit from olaparib.
The latest approval was based on phase 3 OlympiA trial results, which showed a 42% improvement in invasive and distant disease-free survival with olaparib in comparison with placebo. Data from OlympiaA and other clinical studies also confirm BRACAnalysis CDx as “an effective test for patients deciding on their best treatment options,” Myriad Genetics noted in a press release.
The OlympiA results, as reported by this news organization, were presented during the plenary session of the American Society of Clinical Oncology 2021 annual meeting and were published in the New England Journal of Medicine.
Those findings prompted an ASCO “rapid recommendation” updating of ASCO’s 2020 guidelines for the management of hereditary breast cancer.
The latest results from OlympiA show that olaparib reduced the risk of death by 32% (hazard ratio, 0.68) in comparison with placebo, according to a company press release announcing the approval. Overall survival data are slated for presentation at a European Society for Medical Oncology Virtual Plenary session on March 16, 2022.
A version of this article first appeared on Medscape.com.
BRCA+ breast cancer
BRCA+ breast cancer
FDA warns about off-label use of laparoscopic device for aesthetic procedures
The .
The device is cleared by the FDA for “general use of cutting, coagulation, and ablation of soft tissue during open and laparoscopic surgical procedures” but it “has not been determined to be safe or effective for any procedure intended to improve the appearance of the skin,” according to the March 14 statement from the FDA. The statement adds that the agency has received reports describing “serious and potentially life-threatening adverse events with use of this device for certain aesthetic procedures,” including some that have required treatment in an intensive care unit. The statement does not mention whether any cases were fatal.
Adverse events that have been reported include second- and third-degree burns, infections, changes in skin color, scars, nerve damage, “significant bleeding,” and “air or gas accumulation under the skin, in body cavities, and in blood vessels.”
Manufactured by Apyx medical, the device includes a hand piece and generator and uses radiofrequency energy and helium to generate plasma, which is used to “cut, coagulate ... and eliminate soft tissue with heat during surgery,” according to the FDA.
The FDA is advising health care providers not to use the device for dermal resurfacing or skin contraction “alone or in combination with liposuction.”
The statement also advises consumers who are considering an aesthetic skin treatment with this device to consult their health care providers regarding its use – and if they have any problems or are concerned after being treated with this device, to “seek care from a licensed health care provider.”
The FDA is working with Apyx to evaluate information about the use of the device for aesthetic skin procedures and to inform consumers and health care providers about the warning.
Health care providers and consumers should report problems or complications associated with the Renuvion/J-Plasma device to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
The .
The device is cleared by the FDA for “general use of cutting, coagulation, and ablation of soft tissue during open and laparoscopic surgical procedures” but it “has not been determined to be safe or effective for any procedure intended to improve the appearance of the skin,” according to the March 14 statement from the FDA. The statement adds that the agency has received reports describing “serious and potentially life-threatening adverse events with use of this device for certain aesthetic procedures,” including some that have required treatment in an intensive care unit. The statement does not mention whether any cases were fatal.
Adverse events that have been reported include second- and third-degree burns, infections, changes in skin color, scars, nerve damage, “significant bleeding,” and “air or gas accumulation under the skin, in body cavities, and in blood vessels.”
Manufactured by Apyx medical, the device includes a hand piece and generator and uses radiofrequency energy and helium to generate plasma, which is used to “cut, coagulate ... and eliminate soft tissue with heat during surgery,” according to the FDA.
The FDA is advising health care providers not to use the device for dermal resurfacing or skin contraction “alone or in combination with liposuction.”
The statement also advises consumers who are considering an aesthetic skin treatment with this device to consult their health care providers regarding its use – and if they have any problems or are concerned after being treated with this device, to “seek care from a licensed health care provider.”
The FDA is working with Apyx to evaluate information about the use of the device for aesthetic skin procedures and to inform consumers and health care providers about the warning.
Health care providers and consumers should report problems or complications associated with the Renuvion/J-Plasma device to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
The .
The device is cleared by the FDA for “general use of cutting, coagulation, and ablation of soft tissue during open and laparoscopic surgical procedures” but it “has not been determined to be safe or effective for any procedure intended to improve the appearance of the skin,” according to the March 14 statement from the FDA. The statement adds that the agency has received reports describing “serious and potentially life-threatening adverse events with use of this device for certain aesthetic procedures,” including some that have required treatment in an intensive care unit. The statement does not mention whether any cases were fatal.
Adverse events that have been reported include second- and third-degree burns, infections, changes in skin color, scars, nerve damage, “significant bleeding,” and “air or gas accumulation under the skin, in body cavities, and in blood vessels.”
Manufactured by Apyx medical, the device includes a hand piece and generator and uses radiofrequency energy and helium to generate plasma, which is used to “cut, coagulate ... and eliminate soft tissue with heat during surgery,” according to the FDA.
The FDA is advising health care providers not to use the device for dermal resurfacing or skin contraction “alone or in combination with liposuction.”
The statement also advises consumers who are considering an aesthetic skin treatment with this device to consult their health care providers regarding its use – and if they have any problems or are concerned after being treated with this device, to “seek care from a licensed health care provider.”
The FDA is working with Apyx to evaluate information about the use of the device for aesthetic skin procedures and to inform consumers and health care providers about the warning.
Health care providers and consumers should report problems or complications associated with the Renuvion/J-Plasma device to the FDA’s MedWatch program.
A version of this article first appeared on Medscape.com.
FDA approves neoadjuvant nivolumab/chemo for early-stage NSCLC
in combination with platinum-doublet chemotherapy, regardless of PDL-1 status.
Nivolumab is the first immune checkpoint inhibitor to be approved for resectable NSCLC; its three prior NSCLC indications are for metastatic disease, the agency said in its announcement.
Approval was based on the CheckMate 816 trial, which randomized 358 patients evenly to either nivolumab plus platinum doublets or to platinum doublets alone every 3 weeks for up to 3 cycles.
Trial participants had histologically confirmed stage IB, II, or IIIA disease, which was measurable by RECIST criteria. They were enrolled regardless of tumor PD-L1 status.
At surgery, the pathologic complete response rate was 24% in the nivolumab arm versus 2.2% in the chemotherapy-alone group.
Median event-free survival was 31.6 months with nivolumab but 20.8 months without it, which translated to a 37% reduction in the risk for progression, recurrence, or death following surgery. A trend toward better overall survival was not statistically significant, Bristol Myers Squibb said in its own announcement.
Nivolumab’s new neoadjuvant indication is for adult patients with resectable NSCLC (tumors greater than or equal to 4 cm or node positive). The recommended dosage is 360 mg in combination with platinum-doublet chemotherapy on the same day every 3 weeks for three cycles.
In a press release from Bristol Myers Squibb, CheckMate 816 investigator and Dana-Farber Cancer Institute thoracic oncologist Mark Awad, MD, PhD, called the approval “a turning point in how we treat resectable NSCLC.”
Patients with known EGFR mutations or ALK translocations, grade 2 or higher peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded.
There were no fatal adverse events in the nivolumab arm, but 30% of participants had serious adverse events, most commonly pneumonia and vomiting.
The most common side effects across all grades were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%). Surgical complications and hospital lengths were similar between the two study groups.
Rival checkpoint inhibitor pembrolizumab is also being investigated for neoadjuvant NSCLC.
A version of this article first appeared on Medscape.com.
in combination with platinum-doublet chemotherapy, regardless of PDL-1 status.
Nivolumab is the first immune checkpoint inhibitor to be approved for resectable NSCLC; its three prior NSCLC indications are for metastatic disease, the agency said in its announcement.
Approval was based on the CheckMate 816 trial, which randomized 358 patients evenly to either nivolumab plus platinum doublets or to platinum doublets alone every 3 weeks for up to 3 cycles.
Trial participants had histologically confirmed stage IB, II, or IIIA disease, which was measurable by RECIST criteria. They were enrolled regardless of tumor PD-L1 status.
At surgery, the pathologic complete response rate was 24% in the nivolumab arm versus 2.2% in the chemotherapy-alone group.
Median event-free survival was 31.6 months with nivolumab but 20.8 months without it, which translated to a 37% reduction in the risk for progression, recurrence, or death following surgery. A trend toward better overall survival was not statistically significant, Bristol Myers Squibb said in its own announcement.
Nivolumab’s new neoadjuvant indication is for adult patients with resectable NSCLC (tumors greater than or equal to 4 cm or node positive). The recommended dosage is 360 mg in combination with platinum-doublet chemotherapy on the same day every 3 weeks for three cycles.
In a press release from Bristol Myers Squibb, CheckMate 816 investigator and Dana-Farber Cancer Institute thoracic oncologist Mark Awad, MD, PhD, called the approval “a turning point in how we treat resectable NSCLC.”
Patients with known EGFR mutations or ALK translocations, grade 2 or higher peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded.
There were no fatal adverse events in the nivolumab arm, but 30% of participants had serious adverse events, most commonly pneumonia and vomiting.
The most common side effects across all grades were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%). Surgical complications and hospital lengths were similar between the two study groups.
Rival checkpoint inhibitor pembrolizumab is also being investigated for neoadjuvant NSCLC.
A version of this article first appeared on Medscape.com.
in combination with platinum-doublet chemotherapy, regardless of PDL-1 status.
Nivolumab is the first immune checkpoint inhibitor to be approved for resectable NSCLC; its three prior NSCLC indications are for metastatic disease, the agency said in its announcement.
Approval was based on the CheckMate 816 trial, which randomized 358 patients evenly to either nivolumab plus platinum doublets or to platinum doublets alone every 3 weeks for up to 3 cycles.
Trial participants had histologically confirmed stage IB, II, or IIIA disease, which was measurable by RECIST criteria. They were enrolled regardless of tumor PD-L1 status.
At surgery, the pathologic complete response rate was 24% in the nivolumab arm versus 2.2% in the chemotherapy-alone group.
Median event-free survival was 31.6 months with nivolumab but 20.8 months without it, which translated to a 37% reduction in the risk for progression, recurrence, or death following surgery. A trend toward better overall survival was not statistically significant, Bristol Myers Squibb said in its own announcement.
Nivolumab’s new neoadjuvant indication is for adult patients with resectable NSCLC (tumors greater than or equal to 4 cm or node positive). The recommended dosage is 360 mg in combination with platinum-doublet chemotherapy on the same day every 3 weeks for three cycles.
In a press release from Bristol Myers Squibb, CheckMate 816 investigator and Dana-Farber Cancer Institute thoracic oncologist Mark Awad, MD, PhD, called the approval “a turning point in how we treat resectable NSCLC.”
Patients with known EGFR mutations or ALK translocations, grade 2 or higher peripheral neuropathy, active autoimmune disease, or medical conditions requiring systemic immunosuppression were excluded.
There were no fatal adverse events in the nivolumab arm, but 30% of participants had serious adverse events, most commonly pneumonia and vomiting.
The most common side effects across all grades were nausea (38%), constipation (34%), fatigue (26%), decreased appetite (20%), and rash (20%). Surgical complications and hospital lengths were similar between the two study groups.
Rival checkpoint inhibitor pembrolizumab is also being investigated for neoadjuvant NSCLC.
A version of this article first appeared on Medscape.com.
Clozapine interrupted: APA, others seek FDA forum on REMS
In a Feb. 14 letter, the groups asked the FDA to reconsider its new risk evaluation and mitigation strategy (REMS) for clozapine because of concerns it had the potential to cause abrupt discontinuation of the medication.
The groups cite an Institute for Safe Medication Practices (ISMP) report of a 40-year-old woman who was a long-time clozapine user, had a cardiac arrest, and died after she stopped taking the drug because her psychiatrist was unable to register for the updated version of the REMS.
“It is unacceptable for a REMS with unproven effectiveness at meeting its goal to carry risks of interruptions that can result in rehospitalization, acute exacerbation of psychosis, increased risk of suicide, and potentially fatal orthostatic hypotension/bradycardic syndromes associated with incorrect restarts,” the groups said in the letter.
“We feel certain that this case reported in the literature is not the only serious adverse outcome from the REMS and the transition,” they added.
The letter was signed by the American Psychiatric Association, the American Association for Community Psychiatry, the American Psychiatric Nurses Association, the College of Psychiatric and Neurologic Pharmacists, the National Alliance on Mental Illness, the National Association of State Mental Health Program Directors, and the National Council for Mental Wellbeing.
Clozapine can decrease the neutrophil count, which can lead to severe neutropenia, serious infection, and death. Consequently, the FDA put additional safety measures in place governing clozapine prescribing.
In 2015, a centralized clozapine REMS replaced separate prescribing registries that the drug manufacturers maintained. There were technical issues with the 2015 start-up of that website, including data migration problems and long call wait times, the FDA said.
Subsequently, the drug’s manufacturers then decided to change the REMS platform, which created new issues that led to high call volume and long wait times for clinicians and pharmacists who were trying to enroll.
Maintaining access
In November 2021, the FDA announced it would put some aspects of a planned switch on hold. A month later, the agency made further modifications to its plan.
The FDA said it would exercise “enforcement discretion” to try to maintain access to clozapine amid hitches with the REMS transition efforts. The agency also said at the time that it would not object if pharmacists dispensed clozapine without the usual authorization. In addition, wholesalers could ship the drug to pharmacies and health care settings without confirming REMS enrollment.
The FDA also held two December meetings to allow various stakeholders to air concerns.
In their letter, the APA and other groups asked if the FDA intends to continue with accommodations, such as allowing pharmacies to order clozapine from wholesalers without restriction.
“We do not feel the issues are resolved,” the groups said.
A version of this article first appeared on Medscape.com.
In a Feb. 14 letter, the groups asked the FDA to reconsider its new risk evaluation and mitigation strategy (REMS) for clozapine because of concerns it had the potential to cause abrupt discontinuation of the medication.
The groups cite an Institute for Safe Medication Practices (ISMP) report of a 40-year-old woman who was a long-time clozapine user, had a cardiac arrest, and died after she stopped taking the drug because her psychiatrist was unable to register for the updated version of the REMS.
“It is unacceptable for a REMS with unproven effectiveness at meeting its goal to carry risks of interruptions that can result in rehospitalization, acute exacerbation of psychosis, increased risk of suicide, and potentially fatal orthostatic hypotension/bradycardic syndromes associated with incorrect restarts,” the groups said in the letter.
“We feel certain that this case reported in the literature is not the only serious adverse outcome from the REMS and the transition,” they added.
The letter was signed by the American Psychiatric Association, the American Association for Community Psychiatry, the American Psychiatric Nurses Association, the College of Psychiatric and Neurologic Pharmacists, the National Alliance on Mental Illness, the National Association of State Mental Health Program Directors, and the National Council for Mental Wellbeing.
Clozapine can decrease the neutrophil count, which can lead to severe neutropenia, serious infection, and death. Consequently, the FDA put additional safety measures in place governing clozapine prescribing.
In 2015, a centralized clozapine REMS replaced separate prescribing registries that the drug manufacturers maintained. There were technical issues with the 2015 start-up of that website, including data migration problems and long call wait times, the FDA said.
Subsequently, the drug’s manufacturers then decided to change the REMS platform, which created new issues that led to high call volume and long wait times for clinicians and pharmacists who were trying to enroll.
Maintaining access
In November 2021, the FDA announced it would put some aspects of a planned switch on hold. A month later, the agency made further modifications to its plan.
The FDA said it would exercise “enforcement discretion” to try to maintain access to clozapine amid hitches with the REMS transition efforts. The agency also said at the time that it would not object if pharmacists dispensed clozapine without the usual authorization. In addition, wholesalers could ship the drug to pharmacies and health care settings without confirming REMS enrollment.
The FDA also held two December meetings to allow various stakeholders to air concerns.
In their letter, the APA and other groups asked if the FDA intends to continue with accommodations, such as allowing pharmacies to order clozapine from wholesalers without restriction.
“We do not feel the issues are resolved,” the groups said.
A version of this article first appeared on Medscape.com.
In a Feb. 14 letter, the groups asked the FDA to reconsider its new risk evaluation and mitigation strategy (REMS) for clozapine because of concerns it had the potential to cause abrupt discontinuation of the medication.
The groups cite an Institute for Safe Medication Practices (ISMP) report of a 40-year-old woman who was a long-time clozapine user, had a cardiac arrest, and died after she stopped taking the drug because her psychiatrist was unable to register for the updated version of the REMS.
“It is unacceptable for a REMS with unproven effectiveness at meeting its goal to carry risks of interruptions that can result in rehospitalization, acute exacerbation of psychosis, increased risk of suicide, and potentially fatal orthostatic hypotension/bradycardic syndromes associated with incorrect restarts,” the groups said in the letter.
“We feel certain that this case reported in the literature is not the only serious adverse outcome from the REMS and the transition,” they added.
The letter was signed by the American Psychiatric Association, the American Association for Community Psychiatry, the American Psychiatric Nurses Association, the College of Psychiatric and Neurologic Pharmacists, the National Alliance on Mental Illness, the National Association of State Mental Health Program Directors, and the National Council for Mental Wellbeing.
Clozapine can decrease the neutrophil count, which can lead to severe neutropenia, serious infection, and death. Consequently, the FDA put additional safety measures in place governing clozapine prescribing.
In 2015, a centralized clozapine REMS replaced separate prescribing registries that the drug manufacturers maintained. There were technical issues with the 2015 start-up of that website, including data migration problems and long call wait times, the FDA said.
Subsequently, the drug’s manufacturers then decided to change the REMS platform, which created new issues that led to high call volume and long wait times for clinicians and pharmacists who were trying to enroll.
Maintaining access
In November 2021, the FDA announced it would put some aspects of a planned switch on hold. A month later, the agency made further modifications to its plan.
The FDA said it would exercise “enforcement discretion” to try to maintain access to clozapine amid hitches with the REMS transition efforts. The agency also said at the time that it would not object if pharmacists dispensed clozapine without the usual authorization. In addition, wholesalers could ship the drug to pharmacies and health care settings without confirming REMS enrollment.
The FDA also held two December meetings to allow various stakeholders to air concerns.
In their letter, the APA and other groups asked if the FDA intends to continue with accommodations, such as allowing pharmacies to order clozapine from wholesalers without restriction.
“We do not feel the issues are resolved,” the groups said.
A version of this article first appeared on Medscape.com.
FDA approves first drug for myelofibrosis with thrombocytopenia
Pacritinib (Vonjo, CTI BioPharma) is indicated for use in the treatment of adults with intermediate- or high-risk primary or secondary (post–polycythemia vera or post–essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L.
Pacritinib is a novel oral kinase inhibitor with specificity for activity against Janus associated kinase 2 (JAK2) and IRAK1, without inhibiting JAK1. The recommended dosage is 200 mg orally twice daily.
In the United States, there are approximately 21,000 patients with myelofibrosis, notes the manufacturer. About one-third develop severe thrombocytopenia.
“Myelofibrosis with severe thrombocytopenia, defined as blood platelet counts below 50 × 109/L, has been shown to result in poor survival outcomes coupled with debilitating symptoms. Limited treatment options have rendered this disease as an area of urgent unmet medical need,” said John Mascarenhas, MD, associate professor, medicine, hematology, and medical oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York.
“I am pleased to see that a new, efficacious, and safe treatment option is now available for these patients,” he said in a company press release.
Dr. Mascarenhas was the lead investigator of the phase 3 PERSIST-2 trial that was the basis for the approval. Results from the trial were published in 2018 in JAMA Oncology and reported in detail at the time by this news organization.
Authors of an accompanying editorial noted the trial was truncated after the FDA imposed a clinical hold on pacritinib in February 2016 after reports from an earlier trial, PERSIST-1, of patient deaths related to cardiac failure and arrest as well as intracranial hemorrhage. The clinical hold was lifted in January 2017 after the manufacturer provided the FDA with more mature data.
Despite the truncation, the PERSIST-2 trial provided sufficient data to obtain accelerated approval for the drug. The study compared pacritinib with best available therapy (BAT).
In the cohort of patients treated with pacritinib 200 mg twice daily, 29% of patients had a reduction in spleen volume of at least 35% compared with 3% of patients receiving BAT, which included ruxolitinib.
The company is now expected to demonstrate clinical benefit in a confirmatory trial and has the PACIFICA trial underway. Results are expected in mid-2025.
The most common adverse reactions (reported by ≥ 20% of patients) were diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema. The most frequent serious adverse reactions (≥ 3%) were anemia, thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia, and squamous cell carcinoma of the skin.
A version of this article first appeared on Medscape.com.
Pacritinib (Vonjo, CTI BioPharma) is indicated for use in the treatment of adults with intermediate- or high-risk primary or secondary (post–polycythemia vera or post–essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L.
Pacritinib is a novel oral kinase inhibitor with specificity for activity against Janus associated kinase 2 (JAK2) and IRAK1, without inhibiting JAK1. The recommended dosage is 200 mg orally twice daily.
In the United States, there are approximately 21,000 patients with myelofibrosis, notes the manufacturer. About one-third develop severe thrombocytopenia.
“Myelofibrosis with severe thrombocytopenia, defined as blood platelet counts below 50 × 109/L, has been shown to result in poor survival outcomes coupled with debilitating symptoms. Limited treatment options have rendered this disease as an area of urgent unmet medical need,” said John Mascarenhas, MD, associate professor, medicine, hematology, and medical oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York.
“I am pleased to see that a new, efficacious, and safe treatment option is now available for these patients,” he said in a company press release.
Dr. Mascarenhas was the lead investigator of the phase 3 PERSIST-2 trial that was the basis for the approval. Results from the trial were published in 2018 in JAMA Oncology and reported in detail at the time by this news organization.
Authors of an accompanying editorial noted the trial was truncated after the FDA imposed a clinical hold on pacritinib in February 2016 after reports from an earlier trial, PERSIST-1, of patient deaths related to cardiac failure and arrest as well as intracranial hemorrhage. The clinical hold was lifted in January 2017 after the manufacturer provided the FDA with more mature data.
Despite the truncation, the PERSIST-2 trial provided sufficient data to obtain accelerated approval for the drug. The study compared pacritinib with best available therapy (BAT).
In the cohort of patients treated with pacritinib 200 mg twice daily, 29% of patients had a reduction in spleen volume of at least 35% compared with 3% of patients receiving BAT, which included ruxolitinib.
The company is now expected to demonstrate clinical benefit in a confirmatory trial and has the PACIFICA trial underway. Results are expected in mid-2025.
The most common adverse reactions (reported by ≥ 20% of patients) were diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema. The most frequent serious adverse reactions (≥ 3%) were anemia, thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia, and squamous cell carcinoma of the skin.
A version of this article first appeared on Medscape.com.
Pacritinib (Vonjo, CTI BioPharma) is indicated for use in the treatment of adults with intermediate- or high-risk primary or secondary (post–polycythemia vera or post–essential thrombocythemia) myelofibrosis with a platelet count below 50 × 109/L.
Pacritinib is a novel oral kinase inhibitor with specificity for activity against Janus associated kinase 2 (JAK2) and IRAK1, without inhibiting JAK1. The recommended dosage is 200 mg orally twice daily.
In the United States, there are approximately 21,000 patients with myelofibrosis, notes the manufacturer. About one-third develop severe thrombocytopenia.
“Myelofibrosis with severe thrombocytopenia, defined as blood platelet counts below 50 × 109/L, has been shown to result in poor survival outcomes coupled with debilitating symptoms. Limited treatment options have rendered this disease as an area of urgent unmet medical need,” said John Mascarenhas, MD, associate professor, medicine, hematology, and medical oncology, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York.
“I am pleased to see that a new, efficacious, and safe treatment option is now available for these patients,” he said in a company press release.
Dr. Mascarenhas was the lead investigator of the phase 3 PERSIST-2 trial that was the basis for the approval. Results from the trial were published in 2018 in JAMA Oncology and reported in detail at the time by this news organization.
Authors of an accompanying editorial noted the trial was truncated after the FDA imposed a clinical hold on pacritinib in February 2016 after reports from an earlier trial, PERSIST-1, of patient deaths related to cardiac failure and arrest as well as intracranial hemorrhage. The clinical hold was lifted in January 2017 after the manufacturer provided the FDA with more mature data.
Despite the truncation, the PERSIST-2 trial provided sufficient data to obtain accelerated approval for the drug. The study compared pacritinib with best available therapy (BAT).
In the cohort of patients treated with pacritinib 200 mg twice daily, 29% of patients had a reduction in spleen volume of at least 35% compared with 3% of patients receiving BAT, which included ruxolitinib.
The company is now expected to demonstrate clinical benefit in a confirmatory trial and has the PACIFICA trial underway. Results are expected in mid-2025.
The most common adverse reactions (reported by ≥ 20% of patients) were diarrhea, thrombocytopenia, nausea, anemia, and peripheral edema. The most frequent serious adverse reactions (≥ 3%) were anemia, thrombocytopenia, pneumonia, cardiac failure, disease progression, pyrexia, and squamous cell carcinoma of the skin.
A version of this article first appeared on Medscape.com.
FDA approves new CAR T-cell treatment for multiple myeloma
A new treatment option for patients with refractory/relapsed multiple myeloma who have already tried four or more therapies has been approved by the U.S. Food and Drug Administration.
There are already two other therapies on the market that target BCMA – another CAR T cell, idecabtagene vicleucel (Abecma), which was approved by the FDA in March 2021, and a drug conjugate, belantamab mafodotin (Blenrep), which was approved in August 2020.
The approval of cilta-cel was based on clinical data from the CARTITUDE-1 study, which were initially presented in December 2020 at the annual meeting of the American Society of Hematology, as reported at the time by this news organization.
The trial involved 97 patients with relapsed/refractory multiple myeloma who had already received a median of six previous treatments (range, three to 18), including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
“The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse, with fewer patients achieving a deep response as they progress through later lines of therapy,” commented Sundar Jagannath, MBBS, professor of medicine, hematology, and medical oncology at Mount Sinai, who was a principal investigator on the pivotal study.
“That is why I have been really excited about the results from the CARTITUDE-1 study, which has demonstrated that cilta-cel can provide deep and durable responses and long-term treatment-free intervals, even in this heavily pretreated multiple myeloma patient population,” he said.
“Today’s approval of Carvykti helps address a great unmet need for these patients,” he commented in a press release from the manufacturer.
Like other CAR T-cell therapies, ciltacabtagene autoleucel is a one-time treatment. It involves collecting blood from the patient, extracting T cells, genetically engineering them, then transfusing them back to the patient, who in the meantime has undergone conditioning.
The results from CARTITUDE-1 show that this one-time treatment resulted in deep and durable responses.
The overall response rate was 98%, and the majority of patients (78%) achieved a stringent complete response, in which physicians are unable to observe any signs or symptoms of disease via imaging or other tests after treatment.
At a median of 18 months’ follow-up, the median duration of response was 21.8 months.
“The responses in the CARTITUDE-1 study showed durability over time and resulted in the majority of heavily pretreated patients achieving deep responses after 18-month follow-up,” commented Mr. Jagannath.
“The approval of cilta-cel provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time,” he added.
As with other CAR T-cell therapies, there were serious side effects, and these products are available only through restricted programs under a risk evaluation and mitigation strategy.
The product information for Cartykti includes a boxed warning that mentions cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome, parkinsonism, Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged and/or recurrent cytopenias.
The most common adverse reactions (reported in greater than or equal to 20% of patients) are pyrexia, CRS, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections–pathogens unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.
A version of this article first appeared on Medscape.com.
A new treatment option for patients with refractory/relapsed multiple myeloma who have already tried four or more therapies has been approved by the U.S. Food and Drug Administration.
There are already two other therapies on the market that target BCMA – another CAR T cell, idecabtagene vicleucel (Abecma), which was approved by the FDA in March 2021, and a drug conjugate, belantamab mafodotin (Blenrep), which was approved in August 2020.
The approval of cilta-cel was based on clinical data from the CARTITUDE-1 study, which were initially presented in December 2020 at the annual meeting of the American Society of Hematology, as reported at the time by this news organization.
The trial involved 97 patients with relapsed/refractory multiple myeloma who had already received a median of six previous treatments (range, three to 18), including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
“The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse, with fewer patients achieving a deep response as they progress through later lines of therapy,” commented Sundar Jagannath, MBBS, professor of medicine, hematology, and medical oncology at Mount Sinai, who was a principal investigator on the pivotal study.
“That is why I have been really excited about the results from the CARTITUDE-1 study, which has demonstrated that cilta-cel can provide deep and durable responses and long-term treatment-free intervals, even in this heavily pretreated multiple myeloma patient population,” he said.
“Today’s approval of Carvykti helps address a great unmet need for these patients,” he commented in a press release from the manufacturer.
Like other CAR T-cell therapies, ciltacabtagene autoleucel is a one-time treatment. It involves collecting blood from the patient, extracting T cells, genetically engineering them, then transfusing them back to the patient, who in the meantime has undergone conditioning.
The results from CARTITUDE-1 show that this one-time treatment resulted in deep and durable responses.
The overall response rate was 98%, and the majority of patients (78%) achieved a stringent complete response, in which physicians are unable to observe any signs or symptoms of disease via imaging or other tests after treatment.
At a median of 18 months’ follow-up, the median duration of response was 21.8 months.
“The responses in the CARTITUDE-1 study showed durability over time and resulted in the majority of heavily pretreated patients achieving deep responses after 18-month follow-up,” commented Mr. Jagannath.
“The approval of cilta-cel provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time,” he added.
As with other CAR T-cell therapies, there were serious side effects, and these products are available only through restricted programs under a risk evaluation and mitigation strategy.
The product information for Cartykti includes a boxed warning that mentions cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome, parkinsonism, Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged and/or recurrent cytopenias.
The most common adverse reactions (reported in greater than or equal to 20% of patients) are pyrexia, CRS, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections–pathogens unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.
A version of this article first appeared on Medscape.com.
A new treatment option for patients with refractory/relapsed multiple myeloma who have already tried four or more therapies has been approved by the U.S. Food and Drug Administration.
There are already two other therapies on the market that target BCMA – another CAR T cell, idecabtagene vicleucel (Abecma), which was approved by the FDA in March 2021, and a drug conjugate, belantamab mafodotin (Blenrep), which was approved in August 2020.
The approval of cilta-cel was based on clinical data from the CARTITUDE-1 study, which were initially presented in December 2020 at the annual meeting of the American Society of Hematology, as reported at the time by this news organization.
The trial involved 97 patients with relapsed/refractory multiple myeloma who had already received a median of six previous treatments (range, three to 18), including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
“The treatment journey for the majority of patients living with multiple myeloma is a relentless cycle of remission and relapse, with fewer patients achieving a deep response as they progress through later lines of therapy,” commented Sundar Jagannath, MBBS, professor of medicine, hematology, and medical oncology at Mount Sinai, who was a principal investigator on the pivotal study.
“That is why I have been really excited about the results from the CARTITUDE-1 study, which has demonstrated that cilta-cel can provide deep and durable responses and long-term treatment-free intervals, even in this heavily pretreated multiple myeloma patient population,” he said.
“Today’s approval of Carvykti helps address a great unmet need for these patients,” he commented in a press release from the manufacturer.
Like other CAR T-cell therapies, ciltacabtagene autoleucel is a one-time treatment. It involves collecting blood from the patient, extracting T cells, genetically engineering them, then transfusing them back to the patient, who in the meantime has undergone conditioning.
The results from CARTITUDE-1 show that this one-time treatment resulted in deep and durable responses.
The overall response rate was 98%, and the majority of patients (78%) achieved a stringent complete response, in which physicians are unable to observe any signs or symptoms of disease via imaging or other tests after treatment.
At a median of 18 months’ follow-up, the median duration of response was 21.8 months.
“The responses in the CARTITUDE-1 study showed durability over time and resulted in the majority of heavily pretreated patients achieving deep responses after 18-month follow-up,” commented Mr. Jagannath.
“The approval of cilta-cel provides physicians an immunotherapy treatment option that offers patients an opportunity to be free from anti-myeloma therapies for a period of time,” he added.
As with other CAR T-cell therapies, there were serious side effects, and these products are available only through restricted programs under a risk evaluation and mitigation strategy.
The product information for Cartykti includes a boxed warning that mentions cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome, parkinsonism, Guillain-Barré syndrome, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, and prolonged and/or recurrent cytopenias.
The most common adverse reactions (reported in greater than or equal to 20% of patients) are pyrexia, CRS, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections–pathogens unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting.
A version of this article first appeared on Medscape.com.
Why pregnant people were left behind while vaccines moved at ‘warp speed’ to help the masses
Kia Slade was 7 months pregnant, unvaccinated, and fighting for breath, her oxygen levels plummeting, when her son came into the world last May.
A severe case of COVID-19 pneumonia had left Ms. Slade delirious. When the intensive care team tried to place an oxygen mask on her face, she snatched it away, she recalled. Her baby’s heart rate began to drop.
Ms. Slade’s doctor performed an emergency cesarean section at her bedside in the intensive care unit, delivering baby Tristan 10 weeks early. He weighed just 2 pounds, 14 ounces, about half the size of small full-term baby.
But Ms. Slade wouldn’t meet him until July. She was on a ventilator in a medically-induced coma for 8 weeks, and she developed a serious infection and blood clot while unconscious. It was only after a perilous 2½ months in the hospital, during which her heart stopped twice, that Ms. Slade was vaccinated against COVID-19.
“I wish I had gotten the vaccine earlier,” said Ms. Slade, 42, who remains too sick to return to work as a special education teacher in Baltimore. Doctors “kept pushing me to get vaccinated, but there just wasn’t enough information out there for me to do it.”
A year ago, there was little to no vaccine safety data for pregnant people like Ms. Slade, because they had been excluded from clinical trials run by Pfizer, Moderna, and other vaccine makers.
Lacking data, health experts were unsure and divided about how to advise expectant parents. Although U.S. health officials permitted pregnant people to be vaccinated, the World Health Organization in January 2021 actually discouraged them from doing so; it later reversed that recommendation.
The uncertainty led many women to delay vaccination, and only about two-thirds of the pregnant people who have been tracked by the Centers for Disease Control and Prevention were fully vaccinated as of Feb. 5, 2022, leaving many expectant moms at a high risk of infection and life-threatening complications.
More than 29,000 pregnant people have been hospitalized with COVID-19 and 274 have died, according to the CDC.
“There were surely women who were hospitalized because there wasn’t information available to them,” said Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
Vaccine developers say that pregnant people – who have special health needs and risks – were excluded from clinical trials to protect them from potential side effects of novel technologies, including the Pfizer and Moderna mRNA vaccines and formulations made with cold viruses, such as the Johnson & Johnson vaccine.
But a KHN analysis also shows that pregnant people were left behind because including them in vaccine studies would have complicated and potentially delayed the delivery of COVID-19 vaccines to the broader population.
A growing number of women’s health researchers and advocates say that excluding pregnant people – and the months-long delay in recommending that they be immunized – helped fuel widespread vaccine hesitancy in this vulnerable group.
“Women and their unborn fetuses are dying of COVID infection,” said Jane Van Dis, MD, an ob.gyn. at the University of Rochester (N.Y.) Medical Center who has treated many patients like Ms. Slade. “Our failure as a society to vaccinate women in pregnancy will be remembered by the children and families who lost their mothers to this disease.”
New technology, uncertain risks
At the time COVID-19 vaccines were being developed, scientists had very little experience using mRNA vaccines in pregnant women, said Jacqueline Miller, MD, a senior vice president involved in vaccine research at Moderna.
“When you study anything in pregnant women, you have two patients, the mom and the unborn child,” Dr. Miller said. “Until we had more safety data on the platform, it wasn’t something we wanted to undertake.”
But Dr. Offit noted that vaccines have a strong record of safety in pregnancy and he sees no reason to have excluded pregnant people. None of the vaccines currently in use – including the chickenpox and rubella vaccines, which contain live viruses – have been shown to harm fetuses, he said. Doctors routinely recommend that pregnant people receive pertussis and flu vaccinations.
Dr. Offit, the coinventor of a rotavirus vaccine, said that some concerns about vaccines stem from commercial, not medical, interests. Drug makers don’t want to risk that their product will be blamed for any problems occurring in pregnant people, even if coincidental, he said.
“These companies don’t want bad news,” Dr. Offit said.
In the United States, health officials typically would have told expectant mothers not to take a vaccine that was untested during pregnancy, said Dr. Offit, a member of a committee that advises the Food and Drug Administration on vaccines.
Due to the urgency of the pandemic, health agencies instead permitted pregnant people to make up their own minds about vaccines without recommending them.
Women’s medical associations were also hampered by the lack of data. Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine actively encouraged pregnant people to be vaccinated until July 30, 2021, after the first real-world vaccine studies had been published. The CDC followed suit in August of 2021.
“If we had had this data in the beginning, we would have been able to vaccinate more women,” said Kelli Burroughs, MD, the department chair of obstetrics and gynecology at Memorial Hermann Sugar Land Hospital near Houston.
Yet anti-vaccine groups wasted no time in scaring pregnant people, flooding social media with misinformation about impaired fertility and harm to the fetus.
In the first few months after the COVID-19 vaccines were approved, some doctors were ambivalent about recommending them, and some still advise pregnant patients against vaccination.
An estimated 67% of pregnant people today are fully vaccinated, compared with about 89% of people 65 and older, another high-risk group, and 65% of Americans overall. Vaccination rates are lower among minorities, with 65% of expectant Hispanic mothers and 53% of pregnant African Americans fully vaccinated, according to the CDC.
Vaccination is especially important during pregnancy, because of increased risks of hospitalization, ICU admission, and mechanical ventilation, Dr. Burroughs said. A study released in February from the National Institutes of Health found that pregnant people with a moderate to severe COVID-19 infection also were more likely to have a C-section, deliver preterm, or develop a postpartum hemorrhage.
Black moms such as Ms. Slade were already at higher risk of maternal and infant mortality before the pandemic, because of higher underlying risks, unequal access to health care, and other factors. COVID-19 has magnified those risks, said Dr. Burroughs, who has persuaded reluctant patients by revealing that she had a healthy pregnancy and child after being vaccinated.
Ms. Slade said she has never opposed vaccines and had no hesitation about receiving other vaccines while pregnant. But she said she “just wasn’t comfortable” with COVID-19 shots.
“If there had been data out there saying the COVID shot was safe, and that nothing would happen to my baby and there was no risk of birth defects, I would have taken it,” said Ms. Slade, who has had type 2 diabetes for 12 years.
Working at warp speed
Government scientists at the NIH were concerned about the risk of COVID-19 to pregnant people from the very beginning and knew that expectant moms needed vaccines as much or more than anyone else, said Larry Corey, MD, a leader of the COVID-19 Prevention Network, which coordinated COVID-19 vaccine trials for the federal government.
But including pregnant volunteers in the larger vaccine trials could have led to interruptions and delays, Dr. Corey said. Researchers would have had to enroll thousands of pregnant volunteers to achieve statistically robust results that weren’t due to chance, he said.
Pregnancy can bring on a wide range of complications: gestational diabetes, hypertension, anemia, bleeding, blood clots, or problems with the placenta, for example. Up to 20% of people who know they’re pregnant miscarry. Because researchers would have been obliged to investigate any medical problem to make sure it wasn’t caused by one of the COVID-19 vaccines, including pregnant people might have meant having to hit pause on those trials, Dr. Corey said.
With death tolls from the pandemic mounting, “we had a mission to do this as quickly and as thoroughly as possible,” Dr. Corey said. Making COVID-19 vaccines available within a year “saved hundreds of thousands of lives.”
The first data on COVID-19 vaccine safety in pregnancy was published in April of 2021 when the CDC released an analysis of nearly 36,000 vaccinated pregnant people who had enrolled in a registry called V-safe, which allows users to log the dates of their vaccinations and any subsequent symptoms.
Later research showed that COVID-19 vaccines weren’t associated with increased risk of miscarriage or premature delivery.
Brenna Hughes, MD, a maternal-fetal medicine specialist and member of the American College of Obstetricians and Gynecologists’ COVID-19 expert group, agrees that adding pregnant people to large-scale COVID-19 vaccine and drug trials may have been impractical. But researchers could have launched parallel trials of pregnant women, once early studies showed the vaccines were safe in humans, she said.
“Would it have been hard? Everything with COVID is hard,” Dr. Hughes said. “But it would have been feasible.”
The FDA requires that researchers perform additional animal studies – called developmental and reproductive toxicity studies – before testing vaccines in pregnant people. Although these studies are essential, they take 5-6 months, and weren’t completed until late 2020, around the time the first COVID-19 vaccines were authorized for adults, said Emily Erbelding, MD, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases, part of the NIH.
Pregnancy studies “were an afterthought,” said Irina Burd, MD, director of Johns Hopkins’ Integrated Research Center for Fetal Medicine and a professor of gynecology and obstetrics. “They should have been done sooner.”
The NIH is conducting a study of pregnant and postpartum people who decided on their own to be vaccinated, Dr. Erbelding said. The study is due to be completed by July 2023.
Janssen and Moderna are also conducting studies in pregnant people, both due to be completed in 2024.
Pfizer scientists encountered problems when they initiated a clinical trial, which would have randomly assigned pregnant people to receive either a vaccine or placebo. Once vaccines were widely available, many patients weren’t willing to take a chance on being unvaccinated until after delivery.
Pfizer has stopped recruiting patients and has not said whether it will publicly report any data from the trial.
Dr. Hughes said vaccine developers need to include pregnant people from the very beginning.
“There is this notion of protecting pregnant people from research,” Dr. Hughes said. “But we should be protecting patients through research, not from research.”
Recovering physically and emotionally
Ms. Slade still regrets being deprived of time with her children while she fought the disease.
Being on a ventilator kept her from spending those early weeks with her newborn, or from seeing her 9-year-old daughter, Zoe.
Even when Ms. Slade was finally able to see her son, she wasn’t able to tell him she loved him or sing a lullaby, or even talk at all, because of a breathing tube in her throat.
Today, Ms. Slade is a strong advocate of COVID-19 vaccinations, urging her friends and family to get their shots to avoid suffering the way she has.
Ms. Slade had to relearn to walk after being bedridden for weeks. Her many weeks on a ventilator may have contributed to her stomach paralysis, which often causes intense pain, nausea, and even vomiting when she eats or drinks. Ms. Slade weighs 50 pounds less today than before she became pregnant and has resorted to going to the emergency department when the pain is unbearable. “Most days, I’m just miserable,” she said.
Her family suffered as well. Like many babies born prematurely, Tristan, now nearly 9 months old and crawling, receives physical therapy to strengthen his muscles. At 15 pounds, Tristan is largely healthy, although his doctor said he has symptoms of asthma.
Ms. Slade said she would like to attend family counseling with Zoe, who rarely complains and tends to keep her feelings to herself. Ms. Slade said she knows her illness must have been terrifying for her little girl.
“The other day she was talking to me,” Ms. Slade said, “and she said, ‘You know, I almost had to bury you.’ ”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Kia Slade was 7 months pregnant, unvaccinated, and fighting for breath, her oxygen levels plummeting, when her son came into the world last May.
A severe case of COVID-19 pneumonia had left Ms. Slade delirious. When the intensive care team tried to place an oxygen mask on her face, she snatched it away, she recalled. Her baby’s heart rate began to drop.
Ms. Slade’s doctor performed an emergency cesarean section at her bedside in the intensive care unit, delivering baby Tristan 10 weeks early. He weighed just 2 pounds, 14 ounces, about half the size of small full-term baby.
But Ms. Slade wouldn’t meet him until July. She was on a ventilator in a medically-induced coma for 8 weeks, and she developed a serious infection and blood clot while unconscious. It was only after a perilous 2½ months in the hospital, during which her heart stopped twice, that Ms. Slade was vaccinated against COVID-19.
“I wish I had gotten the vaccine earlier,” said Ms. Slade, 42, who remains too sick to return to work as a special education teacher in Baltimore. Doctors “kept pushing me to get vaccinated, but there just wasn’t enough information out there for me to do it.”
A year ago, there was little to no vaccine safety data for pregnant people like Ms. Slade, because they had been excluded from clinical trials run by Pfizer, Moderna, and other vaccine makers.
Lacking data, health experts were unsure and divided about how to advise expectant parents. Although U.S. health officials permitted pregnant people to be vaccinated, the World Health Organization in January 2021 actually discouraged them from doing so; it later reversed that recommendation.
The uncertainty led many women to delay vaccination, and only about two-thirds of the pregnant people who have been tracked by the Centers for Disease Control and Prevention were fully vaccinated as of Feb. 5, 2022, leaving many expectant moms at a high risk of infection and life-threatening complications.
More than 29,000 pregnant people have been hospitalized with COVID-19 and 274 have died, according to the CDC.
“There were surely women who were hospitalized because there wasn’t information available to them,” said Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
Vaccine developers say that pregnant people – who have special health needs and risks – were excluded from clinical trials to protect them from potential side effects of novel technologies, including the Pfizer and Moderna mRNA vaccines and formulations made with cold viruses, such as the Johnson & Johnson vaccine.
But a KHN analysis also shows that pregnant people were left behind because including them in vaccine studies would have complicated and potentially delayed the delivery of COVID-19 vaccines to the broader population.
A growing number of women’s health researchers and advocates say that excluding pregnant people – and the months-long delay in recommending that they be immunized – helped fuel widespread vaccine hesitancy in this vulnerable group.
“Women and their unborn fetuses are dying of COVID infection,” said Jane Van Dis, MD, an ob.gyn. at the University of Rochester (N.Y.) Medical Center who has treated many patients like Ms. Slade. “Our failure as a society to vaccinate women in pregnancy will be remembered by the children and families who lost their mothers to this disease.”
New technology, uncertain risks
At the time COVID-19 vaccines were being developed, scientists had very little experience using mRNA vaccines in pregnant women, said Jacqueline Miller, MD, a senior vice president involved in vaccine research at Moderna.
“When you study anything in pregnant women, you have two patients, the mom and the unborn child,” Dr. Miller said. “Until we had more safety data on the platform, it wasn’t something we wanted to undertake.”
But Dr. Offit noted that vaccines have a strong record of safety in pregnancy and he sees no reason to have excluded pregnant people. None of the vaccines currently in use – including the chickenpox and rubella vaccines, which contain live viruses – have been shown to harm fetuses, he said. Doctors routinely recommend that pregnant people receive pertussis and flu vaccinations.
Dr. Offit, the coinventor of a rotavirus vaccine, said that some concerns about vaccines stem from commercial, not medical, interests. Drug makers don’t want to risk that their product will be blamed for any problems occurring in pregnant people, even if coincidental, he said.
“These companies don’t want bad news,” Dr. Offit said.
In the United States, health officials typically would have told expectant mothers not to take a vaccine that was untested during pregnancy, said Dr. Offit, a member of a committee that advises the Food and Drug Administration on vaccines.
Due to the urgency of the pandemic, health agencies instead permitted pregnant people to make up their own minds about vaccines without recommending them.
Women’s medical associations were also hampered by the lack of data. Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine actively encouraged pregnant people to be vaccinated until July 30, 2021, after the first real-world vaccine studies had been published. The CDC followed suit in August of 2021.
“If we had had this data in the beginning, we would have been able to vaccinate more women,” said Kelli Burroughs, MD, the department chair of obstetrics and gynecology at Memorial Hermann Sugar Land Hospital near Houston.
Yet anti-vaccine groups wasted no time in scaring pregnant people, flooding social media with misinformation about impaired fertility and harm to the fetus.
In the first few months after the COVID-19 vaccines were approved, some doctors were ambivalent about recommending them, and some still advise pregnant patients against vaccination.
An estimated 67% of pregnant people today are fully vaccinated, compared with about 89% of people 65 and older, another high-risk group, and 65% of Americans overall. Vaccination rates are lower among minorities, with 65% of expectant Hispanic mothers and 53% of pregnant African Americans fully vaccinated, according to the CDC.
Vaccination is especially important during pregnancy, because of increased risks of hospitalization, ICU admission, and mechanical ventilation, Dr. Burroughs said. A study released in February from the National Institutes of Health found that pregnant people with a moderate to severe COVID-19 infection also were more likely to have a C-section, deliver preterm, or develop a postpartum hemorrhage.
Black moms such as Ms. Slade were already at higher risk of maternal and infant mortality before the pandemic, because of higher underlying risks, unequal access to health care, and other factors. COVID-19 has magnified those risks, said Dr. Burroughs, who has persuaded reluctant patients by revealing that she had a healthy pregnancy and child after being vaccinated.
Ms. Slade said she has never opposed vaccines and had no hesitation about receiving other vaccines while pregnant. But she said she “just wasn’t comfortable” with COVID-19 shots.
“If there had been data out there saying the COVID shot was safe, and that nothing would happen to my baby and there was no risk of birth defects, I would have taken it,” said Ms. Slade, who has had type 2 diabetes for 12 years.
Working at warp speed
Government scientists at the NIH were concerned about the risk of COVID-19 to pregnant people from the very beginning and knew that expectant moms needed vaccines as much or more than anyone else, said Larry Corey, MD, a leader of the COVID-19 Prevention Network, which coordinated COVID-19 vaccine trials for the federal government.
But including pregnant volunteers in the larger vaccine trials could have led to interruptions and delays, Dr. Corey said. Researchers would have had to enroll thousands of pregnant volunteers to achieve statistically robust results that weren’t due to chance, he said.
Pregnancy can bring on a wide range of complications: gestational diabetes, hypertension, anemia, bleeding, blood clots, or problems with the placenta, for example. Up to 20% of people who know they’re pregnant miscarry. Because researchers would have been obliged to investigate any medical problem to make sure it wasn’t caused by one of the COVID-19 vaccines, including pregnant people might have meant having to hit pause on those trials, Dr. Corey said.
With death tolls from the pandemic mounting, “we had a mission to do this as quickly and as thoroughly as possible,” Dr. Corey said. Making COVID-19 vaccines available within a year “saved hundreds of thousands of lives.”
The first data on COVID-19 vaccine safety in pregnancy was published in April of 2021 when the CDC released an analysis of nearly 36,000 vaccinated pregnant people who had enrolled in a registry called V-safe, which allows users to log the dates of their vaccinations and any subsequent symptoms.
Later research showed that COVID-19 vaccines weren’t associated with increased risk of miscarriage or premature delivery.
Brenna Hughes, MD, a maternal-fetal medicine specialist and member of the American College of Obstetricians and Gynecologists’ COVID-19 expert group, agrees that adding pregnant people to large-scale COVID-19 vaccine and drug trials may have been impractical. But researchers could have launched parallel trials of pregnant women, once early studies showed the vaccines were safe in humans, she said.
“Would it have been hard? Everything with COVID is hard,” Dr. Hughes said. “But it would have been feasible.”
The FDA requires that researchers perform additional animal studies – called developmental and reproductive toxicity studies – before testing vaccines in pregnant people. Although these studies are essential, they take 5-6 months, and weren’t completed until late 2020, around the time the first COVID-19 vaccines were authorized for adults, said Emily Erbelding, MD, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases, part of the NIH.
Pregnancy studies “were an afterthought,” said Irina Burd, MD, director of Johns Hopkins’ Integrated Research Center for Fetal Medicine and a professor of gynecology and obstetrics. “They should have been done sooner.”
The NIH is conducting a study of pregnant and postpartum people who decided on their own to be vaccinated, Dr. Erbelding said. The study is due to be completed by July 2023.
Janssen and Moderna are also conducting studies in pregnant people, both due to be completed in 2024.
Pfizer scientists encountered problems when they initiated a clinical trial, which would have randomly assigned pregnant people to receive either a vaccine or placebo. Once vaccines were widely available, many patients weren’t willing to take a chance on being unvaccinated until after delivery.
Pfizer has stopped recruiting patients and has not said whether it will publicly report any data from the trial.
Dr. Hughes said vaccine developers need to include pregnant people from the very beginning.
“There is this notion of protecting pregnant people from research,” Dr. Hughes said. “But we should be protecting patients through research, not from research.”
Recovering physically and emotionally
Ms. Slade still regrets being deprived of time with her children while she fought the disease.
Being on a ventilator kept her from spending those early weeks with her newborn, or from seeing her 9-year-old daughter, Zoe.
Even when Ms. Slade was finally able to see her son, she wasn’t able to tell him she loved him or sing a lullaby, or even talk at all, because of a breathing tube in her throat.
Today, Ms. Slade is a strong advocate of COVID-19 vaccinations, urging her friends and family to get their shots to avoid suffering the way she has.
Ms. Slade had to relearn to walk after being bedridden for weeks. Her many weeks on a ventilator may have contributed to her stomach paralysis, which often causes intense pain, nausea, and even vomiting when she eats or drinks. Ms. Slade weighs 50 pounds less today than before she became pregnant and has resorted to going to the emergency department when the pain is unbearable. “Most days, I’m just miserable,” she said.
Her family suffered as well. Like many babies born prematurely, Tristan, now nearly 9 months old and crawling, receives physical therapy to strengthen his muscles. At 15 pounds, Tristan is largely healthy, although his doctor said he has symptoms of asthma.
Ms. Slade said she would like to attend family counseling with Zoe, who rarely complains and tends to keep her feelings to herself. Ms. Slade said she knows her illness must have been terrifying for her little girl.
“The other day she was talking to me,” Ms. Slade said, “and she said, ‘You know, I almost had to bury you.’ ”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.
Kia Slade was 7 months pregnant, unvaccinated, and fighting for breath, her oxygen levels plummeting, when her son came into the world last May.
A severe case of COVID-19 pneumonia had left Ms. Slade delirious. When the intensive care team tried to place an oxygen mask on her face, she snatched it away, she recalled. Her baby’s heart rate began to drop.
Ms. Slade’s doctor performed an emergency cesarean section at her bedside in the intensive care unit, delivering baby Tristan 10 weeks early. He weighed just 2 pounds, 14 ounces, about half the size of small full-term baby.
But Ms. Slade wouldn’t meet him until July. She was on a ventilator in a medically-induced coma for 8 weeks, and she developed a serious infection and blood clot while unconscious. It was only after a perilous 2½ months in the hospital, during which her heart stopped twice, that Ms. Slade was vaccinated against COVID-19.
“I wish I had gotten the vaccine earlier,” said Ms. Slade, 42, who remains too sick to return to work as a special education teacher in Baltimore. Doctors “kept pushing me to get vaccinated, but there just wasn’t enough information out there for me to do it.”
A year ago, there was little to no vaccine safety data for pregnant people like Ms. Slade, because they had been excluded from clinical trials run by Pfizer, Moderna, and other vaccine makers.
Lacking data, health experts were unsure and divided about how to advise expectant parents. Although U.S. health officials permitted pregnant people to be vaccinated, the World Health Organization in January 2021 actually discouraged them from doing so; it later reversed that recommendation.
The uncertainty led many women to delay vaccination, and only about two-thirds of the pregnant people who have been tracked by the Centers for Disease Control and Prevention were fully vaccinated as of Feb. 5, 2022, leaving many expectant moms at a high risk of infection and life-threatening complications.
More than 29,000 pregnant people have been hospitalized with COVID-19 and 274 have died, according to the CDC.
“There were surely women who were hospitalized because there wasn’t information available to them,” said Paul A. Offit, MD, director of the Vaccine Education Center at the Children’s Hospital of Philadelphia.
Vaccine developers say that pregnant people – who have special health needs and risks – were excluded from clinical trials to protect them from potential side effects of novel technologies, including the Pfizer and Moderna mRNA vaccines and formulations made with cold viruses, such as the Johnson & Johnson vaccine.
But a KHN analysis also shows that pregnant people were left behind because including them in vaccine studies would have complicated and potentially delayed the delivery of COVID-19 vaccines to the broader population.
A growing number of women’s health researchers and advocates say that excluding pregnant people – and the months-long delay in recommending that they be immunized – helped fuel widespread vaccine hesitancy in this vulnerable group.
“Women and their unborn fetuses are dying of COVID infection,” said Jane Van Dis, MD, an ob.gyn. at the University of Rochester (N.Y.) Medical Center who has treated many patients like Ms. Slade. “Our failure as a society to vaccinate women in pregnancy will be remembered by the children and families who lost their mothers to this disease.”
New technology, uncertain risks
At the time COVID-19 vaccines were being developed, scientists had very little experience using mRNA vaccines in pregnant women, said Jacqueline Miller, MD, a senior vice president involved in vaccine research at Moderna.
“When you study anything in pregnant women, you have two patients, the mom and the unborn child,” Dr. Miller said. “Until we had more safety data on the platform, it wasn’t something we wanted to undertake.”
But Dr. Offit noted that vaccines have a strong record of safety in pregnancy and he sees no reason to have excluded pregnant people. None of the vaccines currently in use – including the chickenpox and rubella vaccines, which contain live viruses – have been shown to harm fetuses, he said. Doctors routinely recommend that pregnant people receive pertussis and flu vaccinations.
Dr. Offit, the coinventor of a rotavirus vaccine, said that some concerns about vaccines stem from commercial, not medical, interests. Drug makers don’t want to risk that their product will be blamed for any problems occurring in pregnant people, even if coincidental, he said.
“These companies don’t want bad news,” Dr. Offit said.
In the United States, health officials typically would have told expectant mothers not to take a vaccine that was untested during pregnancy, said Dr. Offit, a member of a committee that advises the Food and Drug Administration on vaccines.
Due to the urgency of the pandemic, health agencies instead permitted pregnant people to make up their own minds about vaccines without recommending them.
Women’s medical associations were also hampered by the lack of data. Neither the American College of Obstetricians and Gynecologists nor the Society for Maternal-Fetal Medicine actively encouraged pregnant people to be vaccinated until July 30, 2021, after the first real-world vaccine studies had been published. The CDC followed suit in August of 2021.
“If we had had this data in the beginning, we would have been able to vaccinate more women,” said Kelli Burroughs, MD, the department chair of obstetrics and gynecology at Memorial Hermann Sugar Land Hospital near Houston.
Yet anti-vaccine groups wasted no time in scaring pregnant people, flooding social media with misinformation about impaired fertility and harm to the fetus.
In the first few months after the COVID-19 vaccines were approved, some doctors were ambivalent about recommending them, and some still advise pregnant patients against vaccination.
An estimated 67% of pregnant people today are fully vaccinated, compared with about 89% of people 65 and older, another high-risk group, and 65% of Americans overall. Vaccination rates are lower among minorities, with 65% of expectant Hispanic mothers and 53% of pregnant African Americans fully vaccinated, according to the CDC.
Vaccination is especially important during pregnancy, because of increased risks of hospitalization, ICU admission, and mechanical ventilation, Dr. Burroughs said. A study released in February from the National Institutes of Health found that pregnant people with a moderate to severe COVID-19 infection also were more likely to have a C-section, deliver preterm, or develop a postpartum hemorrhage.
Black moms such as Ms. Slade were already at higher risk of maternal and infant mortality before the pandemic, because of higher underlying risks, unequal access to health care, and other factors. COVID-19 has magnified those risks, said Dr. Burroughs, who has persuaded reluctant patients by revealing that she had a healthy pregnancy and child after being vaccinated.
Ms. Slade said she has never opposed vaccines and had no hesitation about receiving other vaccines while pregnant. But she said she “just wasn’t comfortable” with COVID-19 shots.
“If there had been data out there saying the COVID shot was safe, and that nothing would happen to my baby and there was no risk of birth defects, I would have taken it,” said Ms. Slade, who has had type 2 diabetes for 12 years.
Working at warp speed
Government scientists at the NIH were concerned about the risk of COVID-19 to pregnant people from the very beginning and knew that expectant moms needed vaccines as much or more than anyone else, said Larry Corey, MD, a leader of the COVID-19 Prevention Network, which coordinated COVID-19 vaccine trials for the federal government.
But including pregnant volunteers in the larger vaccine trials could have led to interruptions and delays, Dr. Corey said. Researchers would have had to enroll thousands of pregnant volunteers to achieve statistically robust results that weren’t due to chance, he said.
Pregnancy can bring on a wide range of complications: gestational diabetes, hypertension, anemia, bleeding, blood clots, or problems with the placenta, for example. Up to 20% of people who know they’re pregnant miscarry. Because researchers would have been obliged to investigate any medical problem to make sure it wasn’t caused by one of the COVID-19 vaccines, including pregnant people might have meant having to hit pause on those trials, Dr. Corey said.
With death tolls from the pandemic mounting, “we had a mission to do this as quickly and as thoroughly as possible,” Dr. Corey said. Making COVID-19 vaccines available within a year “saved hundreds of thousands of lives.”
The first data on COVID-19 vaccine safety in pregnancy was published in April of 2021 when the CDC released an analysis of nearly 36,000 vaccinated pregnant people who had enrolled in a registry called V-safe, which allows users to log the dates of their vaccinations and any subsequent symptoms.
Later research showed that COVID-19 vaccines weren’t associated with increased risk of miscarriage or premature delivery.
Brenna Hughes, MD, a maternal-fetal medicine specialist and member of the American College of Obstetricians and Gynecologists’ COVID-19 expert group, agrees that adding pregnant people to large-scale COVID-19 vaccine and drug trials may have been impractical. But researchers could have launched parallel trials of pregnant women, once early studies showed the vaccines were safe in humans, she said.
“Would it have been hard? Everything with COVID is hard,” Dr. Hughes said. “But it would have been feasible.”
The FDA requires that researchers perform additional animal studies – called developmental and reproductive toxicity studies – before testing vaccines in pregnant people. Although these studies are essential, they take 5-6 months, and weren’t completed until late 2020, around the time the first COVID-19 vaccines were authorized for adults, said Emily Erbelding, MD, director of microbiology and infectious diseases at the National Institute of Allergy and Infectious Diseases, part of the NIH.
Pregnancy studies “were an afterthought,” said Irina Burd, MD, director of Johns Hopkins’ Integrated Research Center for Fetal Medicine and a professor of gynecology and obstetrics. “They should have been done sooner.”
The NIH is conducting a study of pregnant and postpartum people who decided on their own to be vaccinated, Dr. Erbelding said. The study is due to be completed by July 2023.
Janssen and Moderna are also conducting studies in pregnant people, both due to be completed in 2024.
Pfizer scientists encountered problems when they initiated a clinical trial, which would have randomly assigned pregnant people to receive either a vaccine or placebo. Once vaccines were widely available, many patients weren’t willing to take a chance on being unvaccinated until after delivery.
Pfizer has stopped recruiting patients and has not said whether it will publicly report any data from the trial.
Dr. Hughes said vaccine developers need to include pregnant people from the very beginning.
“There is this notion of protecting pregnant people from research,” Dr. Hughes said. “But we should be protecting patients through research, not from research.”
Recovering physically and emotionally
Ms. Slade still regrets being deprived of time with her children while she fought the disease.
Being on a ventilator kept her from spending those early weeks with her newborn, or from seeing her 9-year-old daughter, Zoe.
Even when Ms. Slade was finally able to see her son, she wasn’t able to tell him she loved him or sing a lullaby, or even talk at all, because of a breathing tube in her throat.
Today, Ms. Slade is a strong advocate of COVID-19 vaccinations, urging her friends and family to get their shots to avoid suffering the way she has.
Ms. Slade had to relearn to walk after being bedridden for weeks. Her many weeks on a ventilator may have contributed to her stomach paralysis, which often causes intense pain, nausea, and even vomiting when she eats or drinks. Ms. Slade weighs 50 pounds less today than before she became pregnant and has resorted to going to the emergency department when the pain is unbearable. “Most days, I’m just miserable,” she said.
Her family suffered as well. Like many babies born prematurely, Tristan, now nearly 9 months old and crawling, receives physical therapy to strengthen his muscles. At 15 pounds, Tristan is largely healthy, although his doctor said he has symptoms of asthma.
Ms. Slade said she would like to attend family counseling with Zoe, who rarely complains and tends to keep her feelings to herself. Ms. Slade said she knows her illness must have been terrifying for her little girl.
“The other day she was talking to me,” Ms. Slade said, “and she said, ‘You know, I almost had to bury you.’ ”
KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. Together with Policy Analysis and Polling, KHN is one of the three major operating programs at KFF (Kaiser Family Foundation). KFF is an endowed nonprofit organization providing information on health issues to the nation.