多发性骨髓瘤中 BCMA 靶向治疗感染并发症的比较

B-cell-maturation-antigen (BCMA)-directed therapies are highly active for multiple myeloma, but infections are emerging as a major challenge. In this retrospective, single-center analysis we evaluated infectious complications after BCMA-targeted chimeric-antigen-receptor T-cell therapy (CAR-T), bispecific-antibodies (BsAb) and antibody-drug-conjugates (ADC). The primary endpoint was severe (grade 3) infection incidence. Amongst 256 patients, 92 received CAR-T, 55 BsAb and 109 ADC. The incidence of severe infections was higher with BsAb (40%) than CAR-T (26%) or ADC (8%), including grade 5 infections (7% vs 0% vs 0%, respectively).

Comparing T-cell redirecting therapies, the incidence rate of severe infections was significantly lower with CAR-T compared to BsAb at 1-year (incidence-rate-ratio [IRR] = 0. 43, 95%CI 0. 25-0. 76, P = 0. 004). During periods of treatment-emergent hypogammaglobulinemia, BsAb recipients had higher infection rates (IRR:2.

27, 1. 31-3. 98, P = 0. 004) and time to severe infection (HR 2. 04, 1. 05-3. 96, P = 0. 036) than their CAR-T counterparts. During periods of non-neutropenia, CAR-T recipients had a lower risk (HR 0. 44, 95%CI 0. 21-0. 93, P = 0. 032) and incidence rate (IRR:0. 32, 95% 0. 17-0. 59, P < 0. 001) of severe infections than BsAb.

In conclusion, we observed an overall higher and more persistent risk of severe infections with BsAb.

Our results also suggest a higher infection risk during periods of hypogammaglobulinemia with BsAb, and with neutropenia in CAR-T recipients.