Sars-Cov-2 Vaccination in the First Year after Hematopoietic Cell Transplant or Chimeric Antigen Receptor T Cell Therapy: A CIBMTR and BMT CTN Study

Background We previously reported the immunogenicity of SARS-CoV-2 vaccination within the first year after allogeneic hematopoietic cell transplant (HCT) from CIBMTR SC21-07/BMT CTN 2101. We herein report updated results from the full allogeneic HCT cohort in addition to the autologous HCT and CAR-T cell therapy cohorts. Methods We conducted a prospective multicenter study of individuals who initiated SARS-CoV-2 vaccinations within 12 months of allogenic HCT, autologous HCT, or CAR-T cell therapy. We obtained blood prior to and after each vaccine dose for up to 4 vaccine doses, with an end-of-study sample 7 to 9 months after enrollment. We tested for SARS-CoV-2 spike protein (anti-S) IgG; nucleocapsid protein (anti-N) IgG; and neutralizing antibodies for Wuhan D614G, Delta B.1.617.2, and Omicron B.1.1.529 strains in all participants (LabCorp), in addition to SARS-CoV-2-specific T-cell receptors (TCRs) in a subgroup (n=151; Adaptive Biotech). We established a relevant threshold for immunogenicity assessment using receiver operating characteristic curves to determine the anti-S IgG threshold predictive of median neutralizing antibody levels (≥5274 ID50) achieved in a non-immunocompromised cohort vaccinated with two doses of mRNA-1273. We compared the proportion of participants with anti-S IgG titers above this threshold among those initiating vaccination <4 months vs 4-12 months after cellular therapy using a propensity-adjusted analysis. Results We enrolled 231 allogeneic HCT, 170 autologous HCT, and 65 CAR-T cell therapy recipients who received ≥1 SARS-CoV-2 vaccine at 34 centers in the U.S. between April 2021 and June 2022; all but 2 received mRNA SARS-CoV-2 vaccines. 231 (50%) participants were vaccinated <4 months after HCT and 235 (50%) 4–12 months after HCT. Most participants (n=352, 76%) received ≥3 vaccine doses. SARS-CoV-2 anti-S IgG titers, neutralizing antibody titers, and TCR responses did not significantly differ following second vaccination among those initiating vaccinations <4 months vs 4-12 months after cellular therapy (Fig. 1-2). Anti-S IgG ≥2,500 U/mL was highly correlated with median neutralizing antibody levels achieved in non-immunocompromised individuals in the HCT cohorts (AUCs ≥89%) and moderately correlated in the CAR-T cohort (73%). These levels were attained in 72%, 74%, and 49% of allogeneic HCT, autologous HCT, and CAR-T cell therapy recipients by the last time point. Qualitative and quantitative TCR responses were generally highest in autologous HCT recipients and lowest in CAR-T cell therapy recipients (Fig. 1C, 3). Grade ≥3 vaccine-associated adverse events were infrequent. Conclusions These data support starting mRNA SARS-CoV-2 vaccination three months after allogeneic HCT, autologous HCT, and CAR-T cell therapy. CAR-T cell therapy recipients appear to have the lowest humoral and cellular responses to SARS-CoV-2 vaccination.