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

Karthik Nath, Tala Shekarkhand, David Nemirovsky, Andriy Derkach, Bruno Almeida Costa, Noriko Nishimura, Tasmin Farzana, Colin Rueda, David J. Chung, Heather J. Landau, Oscar B. Lahoud, Michael Scordo, Gunjan L. Shah, Hani Hassoun, Kylee Maclachlan, Neha Korde, Urvi A. Shah, Carlyn Rose Tan, Malin Hultcrantz, Sergio A. GiraltSaad Z. Usmani, Zainab Shahid, Sham Mailankody, Alexander M. Lesokhin

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Article number88
JournalBlood Cancer Journal
Volume14
Issue number1
DOIs
StatePublished - Dec 2024

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