Efficacy and safety of the Pfizer/BioNTech COVID-19 vaccine in haematopoietic stem cell transplant and CAR-T cell therapy recipients

The safety and efficacy of the Pfizer/BioNTech BNT162b2 COVID-19 vaccine is undetermined in patients who had recently received a haematopoietic stem cell transplant (HSCT) or CAR-T cell therapy infusion. A single centre study, conducted in Israel, reports encouraging safety data in this population, although rates of efficacy varied between HSCT and CAR-T recipients.

Patients who receive allogeneic haematopoietic stem cell transplant (HSCT) or CAR-T cell therapy have an increased risk of severe disease and death, when infected with COVID-19. As a result, these vulnerable patients greatly require a COVID-19 vaccine. However, at present, information regarding safety or efficacy of the mRNA vaccine BNT162b2, developed by Pfizer/BioNTech, in patients undergoing immunologic cell therapy are scarce. At EHA 2021, a study that evaluated the safety and immunogenicity of the BNT162b2 vaccine in patients that underwent either haematopoietic cell transplantation (HSCT) or CAR-T therapy was presented.

Study design

This single-centre study from the Tel Aviv Sourasky Medical Centre enrolled 66 allogeneic HSCT patients and 14 CAR-T cell therapy patients who had received their infusion at least 3 months prior to vaccine referral. Patients were vaccinated through the national Israeli vaccination program that started mid December 2020. Lymphocyte subpopulations (CD19+, CD4+, CD8+) were assessed pre-vaccination. General vaccine adverse events (AEs), haematologic toxicity and graft-versus-host disease (GvHD) were evaluated after the first and second vaccine dose. The humoral immune response to vaccine was evaluated 7-14 days after the second vaccine dose by in vitro quantitative determination of anti-SARS-CoV-2S antibodies using Elecsys® assay and cellular immune response by ELISpot, estimating IL-2 and IFN-gamma secretion in response to a pool of lyophilized SARS-COV-2 S and M peptides (PepTivator; Miltenyi). Primary endpoints of the trial were the incidence of grade 3-4 adverse events (AEs) and GvHD exacerbation.

Variation in humoral immune response

The median age of patients in this study was 65 years and the median number of months from infusion to vaccination were 32 and 9 months for HSCT and CAR-T patients, respectively. At time of enrolment, 58% of patients with GvHD were on active immunosuppressive therapy and 11.3% of all patients had complete B cell aplasia. Encouragingly, the two vaccine doses were well tolerated and adverse events were comparable to a non-transplant population. Overall AEs were experienced by 39% (4.6% grade ≥3) of HSCT patients, and 32% (7% grade ≥3) of CAR-T patients. All events resolved after a few days, except from one case of secondary graft rejection, which is under investigation. In total, 5% of patients had GvHD exacerbation after each vaccine dose. However, these were either self-limited or easily controlled with a low dose of corticosteroids. Cytopenia occurred in 10% of the patients and 5% of the patients developed transient grade 3-4 cytopenia.

Humoral antibody response was documented in 82% of the patients after allogeneic HSCT and in 36% of patients after CAR-T therapy. Conversely, cellular response was lower in HSCT patients compared to CAR-T patients; 46% vs. 79%. The overall responses were 86% and 79%, respectively. In both patient subgroups, those with a CD19+ lymphocyte count >0 had a higher chance of developing antibodies, compared to those with B cell aplasia (67% vs. 12.5%, p=0.036). Through multivariate analysis, factors associated with positive serology included an increased time from infusion of cells (Beta: 1.05, p=0.032), being female (Beta: 0.262, p=0.028) and increased CD19+ cell count (Beta: 1.88, p=0.047). Factors associated with a positive ELISpot test included increased CD19+ (Beta: 1.05, p=0.049) and CD4+ cells (Beta: 1.06, p=0.041). Ongoing GvHD and concomitant immunosuppressive therapy did not affect response.

Conclusion

The Pfizer/BioNTech vaccine appears safe in HSCT and CAR-T cell recipients, with AEs comparable to a non-haematological cohort. However, humoral response to the BNT162b2 mRNA COVID-19 vaccine in CAR-T patients with B cell aplasia is significantly impaired, while overall response in patients after allogeneic HSCT is encouraging. Response is also affected by time from infusion of cells and the level of CD19+ and CD4+ reconstitution. Longer follow-up is required to assess the persistence of antibodies.

Reference

Ram R, et al., Safety and efficacy of the BNT162B2 mRNA COVID-19 vaccine in patients after allogeneic HSCT and CD19-based CAR-T therapy – a single center prospective cohort study. Presented at EHA 2021; abstract S285.