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Immune Deficiencies Present Following Anti-BCMA CAR-T Cell Therapy in R/R MM
A greater understanding of systematic and dynamic humoral immune reconstitution is necessary for patients with relapsed/refractory (R/R) multiple myeloma (MM) who received anti-B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell therapy.
“We investigated the kinetics of B-cell, normal plasma cell, and immunoglobulin recovery in 40 patients who achieved ongoing response after anti-BCMA CAR-T cell therapy,” explained Ying Wang, MD, The Affiliated Hospital of Xuzhou Medical University, China, and co-investigators.
Every patient developed B-cell aplasia and the median duration was 70 days (23-270). Further, B-cell count reached a median low on day 7 and returned to baseline at around day 97.
BCMA positive cells in bone marrow turned undetectable at day 28 (13-159) in 94.87% (37/39) of patients. Normal plasma cells in bone marrow became first re-detectable at day 212. All patients experienced a significant decrease in serum IgG and IgM at day 60.
“Recovery of serum IgG, IgM, and IgA was observed in 53.33% (8/15) patients, (non-IgG MM), 73.08% (19/26) patients (non-IgM MM), and 23.81% (5/21) patients (non-IgA MM) at 1 year, respectively,” continued Dr Wang, et al.
Median times to IgG, IgM, and IgA recovery were on day 386, 254, and not reached upon follow-up, respectively. Virus-specific IgG levels decreased with loss of protection.
23 of 40 (57.5%) patients developed a total of 44 infectious events. There were no reported infection-related deaths.
“These results reveal a 7-month aplasia of bone marrow normal plasma cells and a longer hypogammaglobulinemia, suggesting a profound and lasting humoral immune deficiency after anti-BCMA CAR-T cell therapy, especially for IgA,” concluded Dr Wang, et al. – Alexa Stoia
