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

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

Authors:	Nath, K.; Shekarkhand, T.; Nemirovsky, D.; Derkach, A.; Costa, B. A.; Nishimura, N.; Farzana, T.; Rueda, C.; Chung, D. J.; Landau, H. J.; Lahoud, O. B.; Scordo, M.; Shah, G. L.; Hassoun, H.; Maclachlan, K.; Korde, N.; Shah, U. A.; Tan, C. R.; Hultcrantz, M.; Giralt, S. A.; Usmani, S. Z.; Shahid, Z.; Mailankody, S.; Lesokhin, A. M.
Article Title:	Comparison of infectious complications with BCMA-directed therapies in multiple myeloma
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. © The Author(s) 2024.
Keywords:	adult; controlled study; aged; aged, 80 and over; middle aged; retrospective studies; major clinical study; neutropenia; cancer recurrence; nonhuman; comparative study; cancer immunotherapy; infection; multiple myeloma; incidence; cohort analysis; immunoglobulin; herpes simplex; herpes zoster; pneumocystis pneumonia; recurrent infection; retrospective study; lymphocytopenia; immunology; antiinfective agent; bacteremia; virus infection; bloodstream infection; infection prevention; epidemiology; bacterial infection; immunoglobulin deficiency; granulocyte colony stimulating factor; cytomegalovirus infection; mycosis; therapy; adoptive immunotherapy; immunotherapy, adoptive; infection risk; skin infection; upper respiratory tract infection; opportunistic infection; virus reactivation; infectious complication; recipient; etiology; molecularly targeted therapy; adverse event; bacterial pneumonia; antibody conjugate; immunoconjugates; stenotrophomonas maltophilia; gastrointestinal infection; parasitosis; soft tissue infection; urogenital tract infection; infection rate; infections; gram negative infection; antibodies, bispecific; refractory cancer; bispecific antibody; lower respiratory tract infection; enterobacter aerogenes; very elderly; humans; human; male; female; article; b cell maturation antigen; enterobacteriaceae infection; antibody drug conjugate; b-cell maturation antigen; chimeric antigen receptor t-cell immunotherapy; coronavirus disease 2019; cell therapy agent; pseudomonas pneumonia; tnfrsf17 protein, human; infection severity; klebsiella pneumoniae infection
Journal Title:	Blood Cancer Journal
Volume:	14
ISSN:	2044-5385
Publisher:	Nature Publishing Group
Date Published:	2024-05-31
Start Page:	88
Language:	English
DOI:	10.1038/s41408-024-01043-5
PUBMED:	38821925
PROVIDER:	scopus
PMCID:	PMC11143331
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85195007280&doi=10.1038%2fs41408-024-01043-5&partnerID=40&md5=068ea9f95ff2dca1b04206cd8cf765bc
Notes:	The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding authors are MSK authors: Sham Mailankody and Alexander M. Lesokhin -- Source: Scopus