Comparison of infectious complications with BCMA-directed therapies in multiple myeloma

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Abstract
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.
Funding Information
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute (P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748, P30 CA008748)
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute
  • U.S. Department of Health & Human Services | NIH | National Cancer Institute

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