Timing of Vaccination Impacts Serological Response to COVID-19 Myeloma Patients after BCMA-Targeted CAR T

• Published in: Blood 2023-11, Vol.142 (Supplement 1), p.3350-3350
• Main Authors: Van Oekelen, Oliver, Van Kesteren, Morgan, Aleman, Adolfo, Kogan Zajdman, Ariel, Chen, Lucia Y, Mouhieddine, Tarek H., Upadhyaya, Bhaskar, Serebryakova, Kseniya, Kappes, Katerina, Agte, Sarita, Oostenink, Annika, Jackson, Hayley, Gleason, Charles, Srivastava, Komal, Thibaud, Santiago, Sanchez, Larysa, Rodriguez, Cesar, Richter, Joshua, Cho, Hearn Jay, Rossi, Adriana C, Richard, Shambavi, Cordon-Cardo, Carlos, Wajnberg, Ania, Krammer, Florian, Jagannath, Sundar, Simon, Viviana, Parekh, Samir
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2023-184409

Whereas COVID-19 mRNA vaccines have shown remarkable efficacy in the prevention of severe disease and mortality in healthy individuals, the effectiveness in cancer patients has been more variable. Patients with multiple myeloma (MM) are at a high risk for severe infection due to disease- or treatment-related immune suppression. Our prior work demonstrated that the immune response to SARS-CoV-2 immunization in MM patients with 2 doses of mRNA vaccine was suboptimal and that a 3rd dose significantly improved neutralization of viral variants. MM patients undergoing treatment targeting BCMA were among those at a higher risk of ineffective immune responses. As BCMA-targeted (CAR T) treatment becomes more widely available, guidance on initiation of vaccination after treatment is needed. To assess the impact of BCMA-targeted CAR T (BCMA CAR T) on the serological immune response to COVID-19, we studied 45 MM patients who received ≥1 dose of a COVID-19 mRNA vaccine after prior BCMA CAR T. We collected demographics, disease/treatment characteristics, and COVID-19 infection/vaccination data via retrospective chart review. We analyzed SARS-CoV-2 spike-binding (anti-spike) IgG level using a validated assay (FDA/EUA approved Kantaro). Cumulative incidence of COVID-19 was analyzed using Kaplan-Meier statistics. All subjects were enrolled to studies approved by the Institutional Review Board at a single US academic hospital. Our cohort consisted of 16 women and 29 men with a median age of 61 years. The patients had received a median 6 lines of treatment and 33/45 (73%) had an ongoing response to BCMA CAR T. Patients received dose 1 at median 567 days after CAR T infusion (range 73-1,374 days). 36 patients (80%) received ≥3 doses and 17 (38%) received ≥4 doses. Across the cohort, anti-spike IgG levels increased from median 8 AU/mL after a single dose to 91, 474 and 612 AU/mL after 2, 3 or 4 mRNA vaccine doses respectively. After 2 doses, 6 patients (of 28 for which the timepoint was available, 21%) had no detectable anti-spike IgG levels, whereas all patients in the cohort had a detectable serological response after ≥3 vaccine doses. We compared the 13 patients (29%) that initiated mRNA vaccination at 12 mo. In the early vaccination group, anti-spike IgG levels were significantly lower when measured 0-3 months after 2 vaccine doses (p