Humoral immune reconstitution after anti-BCMA CAR-T cell therapy in relapse/refractory multiple myeloma.

Systematic and dynamic humoral immune reconstitution is little known for relapse/refractory (R/R) multiple myeloma (MM) patients 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. All patients developed B-cell aplasia and the median duration of B-cell aplasia was 70 days (23-270). B cell count reached nadir on a median of day 7 and returned to baseline level on a median of day 97. BCMA positive cells in bone marrow turned undetectable on a median time of day 28 (13-159) in 94.87% (37/39) patients. Normal plasma cells in bone marrow were first re-detectable on a median of day 212. All patients developed a significant decrease in serum IgG, IgA, and IgM on a median of 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. Median times to IgG, IgM and IgA recovery were on day 386, 254 and not reached during follow-up, respectively. Virus-specific IgG levels decreased with loss of protection. Twenty-three of 40 (57.5%) patients developed a total of 44 infection events. No 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.