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Pfizer/BioNTech COVID-19 vaccine seems effective, safe in HCT, CART therapy patients

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Transplantation and Cellular Therapy

Reuters Health – 12/07/2021 – The BNT162b2 mRNA COVID-19 vaccine (Pfizer/BioNTech) elicited an immune response and seemed safe in a small cohort analysis of hematopoietic cell transplantation and CART therapy patients, but hematologic adverse events signaled the need for close monitoring.

“Other vaccines in this population are associated with a 30%-40% response rate,” Dr. Ron Ram of Tel Aviv Sourasky Medical Center in Israel told Reuters Health by email. “We were surprised that the BNT162b2 mRNA COVID-19 vaccine was associated with a much higher response rate of 70%-80%.”

“Nevertheless,” he noted, “like in other vaccines, CAR-T patients with CD19 aplasia had an inferior response to the vaccine, and this was also true for patients with a shorter time after allogeneic hematopoietic cell transplantation (HCT).”

“In addition, clinicians should cautiously monitor blood counts in patients with low baseline counts and also make sure graft-versus-host disease (GVHD) does not exacerbate in the first 1-2 weeks after vaccination.”

As reported in Transplantation and Cellular Therapy, Dr. Ram and colleagues analyzed safety and immunogenicity of the BNT162b2 mRNA vaccine in 66 patients who underwent allogeneic HCT and 14 who received CD19-based received CART therapy. The median age was 65 and 45% were women. The median number of months from allogenic HCT was 32, and from CART, five.

After their allografts, 62% of patients had active chronic GVHD and 58% were on active immunosuppressive therapy.

Complete B cell aplasia was documented in nine patients (11.3%) – eight after CART infusion, and one after allogenic HCT with ongoing severe chronic GVHD.

Overall, the vaccine was well tolerated, with mild non-hematologic adverse events. However, cytopenia developed in 12% of patients after the first vaccine dose and 10%, after the second. There were three cases of GVHD exacerbation after each dose, and a single case of impending graft rejection was considered possibly related.

An immunogenicity evaluation showed that 57% of patients after CART infusion and 75% after allogeneic HCT had evidence of a humoral and/or cellular response to the vaccine.

In a Cox regression model, longer time from infusion of cells, female sex, and higher CD19+ cells were associated with a positive humoral response; a higher CD4+/CD8+ ratio was correlated with a positive cellular response.

Dr. Ram said, “We hypothesize that response to the vaccine may improve if patients without a positive response are given a boost, and this is our current plan.”

Three oncologists commented in emails to Reuters Health about their clinical experiences with COVID-19 vaccinations in these vulnerable patients.

Dr. Meenakshi Rana, Director of Transplant Infectious Disease at Mount Sinai Health System in New York City, said, “We recommend that transplant recipients be vaccinated for COVID 19, and these data help to support that recommendation.” However, larger studies are needed to verify the immunogenicity findings, “including assessing the rate of breakthrough infections and severe disease and hospitalizations.”

“These data will provide us with a better understanding of real-world vaccine efficacy,” he added. “This is especially important as it remains unclear what level of antibody response actually correlates with protection from infection and severe disease.”

Dr. Zeinab El Boghdadly, an infectious disease physician at The Ohio State University Wexner Medical Center in Columbus, commented, “Some of our patients are unable to elicit post-vaccination humoral response with good antibody production due to their impaired immune system. However, we noticed that those who develop infection after vaccination did not necessarily have severe illnesses, which could indicate that vaccination is providing some protection.”

“Absence of humoral response to vaccination does not necessary translate to complete lack of protection, as patients can still mount some sort of cellular immunity,” she said. “But tools to measure that are not routinely available outside research settings.”

Dr. Adrienne Phillips, a hematologist/oncologist at Weill Cornell Medicine and NewYork-Presbyterian in New York City, said, “COVID-19 vaccination has not yet been reported in patients less than three months post-cellular therapy, those that have active GVHD, or in those who are not in a remission post-cellular therapy. They may be least likely to respond to vaccination.”

“For patients who have had a more distant cellular therapy, are in remission, and who are not receiving strong immunosuppressive therapies, this study is encouraging,” she said. “Patients and doctors must discuss each individual case to determine the best recommendation, and all patients really must continue to use COVID19 precautions.”

SOURCE: https://bit.ly/3k9t0Gg Transplantation and Cellular Therapy, online June 30, 2021.

By Marilynn Larkin



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