Safety and Immunogenicity of the BNT162b2 mRNA COVID-19 Vaccine in Patients after Allogeneic HCT or CD19-based CART therapy—A Single-Center Prospective Cohort Study

Abstract

Data are scarce regarding both safety and immunogenicity of the BNT162b2 mRNA COVID-19 vaccine in patients undergoing immune cell therapy, thus we prospectively evaluated these 2 domains in patients receiving this vaccine after allogeneic HCT (n=66) or after CD19-based CART therapy (n=14). Overall, vaccine was well tolerated, with mild non-hematologic vaccine-reported adverse events in minority of the patients. 12% (after first dose) and 10% (after second dose) of the patients developed cytopenia and there were 3 cases GVHD exacerbation after each dose. A single case of impending graft rejection was summarized as possibly related. Evaluation of immunogenicity showed that 57% of patients after CART infusion and 75% patients after allogeneic HCT had evidence of humoral and/or cellular response to the vaccine. On cox regression model, longer time from infusion of cells, female sex, and higher CD19 + cells were associated with a positive humoral response, whereas higher CD4 + /CD8 + ratiowas correlated with a positive cellular response, confirmed by ELISpot test. We conclude that BNT162b2 mRNA COVID-19 vaccine has impressive immunogenicity in patients after allogeneic HCT or CART. Adverse events were mostly mild and transient, but some significant hematologic events were observed, hence, patients should be closely monitored.

Predictors of Humoral Response to SARS-CoV-2 Vaccination after Hematopoietic Cell Transplantation and CAR T-cell Therapy

“…This is in agreement with findings reported by Greenberg et al (21) in a non-transplant hematologic malignancies cohort, indicating a lower response to the vaccine among patients treated with B cells directed therapies. Additionally, In a cohort of 80 patients post cellular therapies, Ram et al (16) observed an association between higher CD19 levels and humoral response to the vaccine, while a higher CD4 + /CD8 + ratio was associated with a cellular response. In another recent publication evaluating patients post cellular therapies, Dhakal et al (22) reported on a cohort of 130 patients and did not find a statistically significant association between immune recovery.…”

“…However, among patients with malignancies (10,11) and recipients of solid organ transplantation (12)(13)(14) emerging data suggest lower vaccine efficacy compared to the healthy population. Data for patients undergoing cellular therapies are sparse, with small studies reporting attenuated humoral and/or cellular immune responses (15)(16)(17). We therefore aimed to assess immune responses to mRNA COVID-19 vaccines among patients who underwent cellular therapies at our center, with the goal of identifying predictors of response, determining the ideal timing for vaccination, and to identify patients at high risk for non-protective immune responses who might benefit from additional doses ('boosters') of vaccines.…”

BNT162b2 mRNA COVID-19 vaccination in immunocompromised patients: A prospective cohort study

“…The latter group consisted of the 45% of HSCT patients who were no longer on immunosuppressive treatment. A recent study on 66 patients after allogeneic HSCT found evidence of a humoral and/or cellular response to the vaccine in 75% [28] .…”

Humoral Immunity After mRNA SARS-CoV-2 Vaccination in Allogeneic HCT Recipients—Room for Improvement and Much to Learn

“…In a comparably designed study including allogeneic HCT recipients receiving a 2-dose mRNA SARS-CoV-2 vaccine regimen and tested with the same serologic assay, seroconversion was observed in 75% of 57 tested participants, with median titers of 178 AU/mL. 3 SARS-CoV-2-specific T-cell responses were documented by enzyme-linked immune absorbent spot assay in 19% of 37 tested individuals, all of whom also seroconverted. As in the current study, the majority of participants were also more than 12 months post-HCT, and seroconversion was positively associated with longer duration since HCT.…”