In a small single-institution study reported in a research letter in JAMA Oncology, Parvathaneni et al found that SARS–CoV-2 mRNA vaccination produced antibody responses in nearly half—and CD4 T-cell responses in more than half—of patients with B-cell depletion due to treatment with B-cell–targeting chimeric antigen receptor (CAR) T-cell therapy.
As stated by the investigators, “Recent studies have demonstrated a substantially lower rate of antibody induction by both SARS–CoV-2 mRNA vaccines among patients with immunosuppression, including individuals with cancer. However, the immunogenicity of SARS–CoV-2 mRNA vaccines among patients with selective B-cell deficiency is not well-known.”
Study Details
The study enrolled 12 patients at the University of Pennsylvania’s Perelman School of Medicine who achieved complete remission after receiving CAR T-cell treatments targeting either the CD19 antigen (n = 7) or the CD19 and CD22 combination (n = 5), as well as 8 healthy adults as controls. All participants received two doses of either the BNT162b2 or mRNA-1273 vaccine. SARS–CoV-2 spike receptor binding domain (RBD) antibodies and spike-specific T-cell responses were measured in blood samples obtained at up to five time points, up to 28 days after the second vaccine dose.
Although this study is limited by its small sample size, we show that immune responses to SARS–CoV-2 mRNA vaccines are induced for the majority of patients who have been treated with CAR T-cell therapies targeting B-cell lineage antigens... Currently, we support SARS–CoV-2 vaccination for all recipients of anti–B-cell CAR T-cell therapies, with close monitoring for immunologic responses to verify our findings in larger cohorts.— Parvathaneni et al
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Key Findings
Spike-specific RBD-IgG was produced in all 8 healthy controls vs 5 of 12 patients who had received CAR T-cell therapy. At 28 days after the second dose, when antibody responses were highest in both groups, RBD-IgG levels were significantly higher (P < .001) in the control vs patient groups; median optical density at 450 nm was 1.57 (interquartile range [IQR] =1.53–1.64) vs 0.47 (IQR = 0.11–1.36).
As anticipated, in the patient cohort, RBD-IgG positivity was associated with higher circulating B-cell levels: mean B-cell counts/μL were 57.2 for RBD-IgG–positive, 12.5 for RBD-IgG–equivocal, and 9 for RBD-IgG–negative patients (P < .05 for RBD-IgG–positive vs –negative). RBD-IgA was detected in 7 of 8 controls vs 2 of 12 patients.
Strong spike-specific CD4 T-cell responses were found in all 8 controls and in 8 of 12 patients. At 28 days after the second dose, there was no significant difference in CD4 T-cell levels between the control and patient cohorts (Cohen d effect size = 0.30, P = .66). Strong CD4 T-cell responses were observed in four patients with substantial B-cell depletion who did not exhibit antibody response. There was no difference in kinetics of T-cell response between controls and patients as represented by predicted slopes over time (6.3% vs 5.5% per visit, P = .63).
The investigators stated, “Although this study is limited by its small sample size, we show that immune responses to SARS–CoV-2 mRNA vaccines are induced for the majority of patients who have been treated with CAR T-cell therapies targeting B-cell lineage antigens. An induction of a vaccine-specific antibody was associated with the level of circulating B cells. However, strong CD4 T-cell responses were observed even for some patients with severe humoral immune deficiency. Further refinement of vaccination strategies to promote cell-mediated immunity may enhance immune protection for individuals with B-cell deficiency. Currently, we support SARS–CoV-2 vaccination for all recipients of anti–B-cell CAR T-cell therapies, with close monitoring for immunologic responses to verify our findings in larger cohorts.”
Vijay G. Bhoj, MD, PhD, of the Department of Pathology and Laboratory Medicine, Center for Cellular Immunotherapies, Perelman School of Medicine, University of Pennsylvania, is the corresponding author for the JAMA Oncology article.
Disclosure: The study was supported by the Gift of Life Transplant Foundation, National Blood Foundation, and Burroughs Wellcome Fund. For full disclosures of the study authors, visit jamanetwork.com.
