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

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), bisp...

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Published in:Blood cancer journal (New York) Vol. 14; no. 1; pp. 88 - 8
Main Authors: Nath, Karthik, Shekarkhand, Tala, Nemirovsky, David, Derkach, Andriy, Costa, Bruno Almeida, Nishimura, Noriko, Farzana, Tasmin, Rueda, Colin, Chung, David J., Landau, Heather J., Lahoud, Oscar B., Scordo, Michael, Shah, Gunjan L., Hassoun, Hani, Maclachlan, Kylee, Korde, Neha, Shah, Urvi A., Tan, Carlyn Rose, Hultcrantz, Malin, Giralt, Sergio A., Usmani, Saad Z., Shahid, Zainab, Mailankody, Sham, Lesokhin, Alexander M.
Format: Journal Article
Language:English
Published: London Nature Publishing Group UK 31.05.2024
Springer Nature B.V
Nature Publishing Group
Subjects:
692/699/255
692/699/67/1990/804
Adult
Aged
Aged, 80 and over
Antibodies, Bispecific - adverse effects
Antibodies, Bispecific - therapeutic use
Antigens
B-Cell Maturation Antigen - immunology
Biomedical and Life Sciences
Biomedicine
Cancer Research
Female
Hematology
Humans
Immunoconjugates - adverse effects
Immunoconjugates - therapeutic use
Immunotherapy, Adoptive - adverse effects
Incidence
Infections
Infections - epidemiology
Infections - etiology
Male
Middle Aged
Multiple myeloma
Multiple Myeloma - therapy
Neutropenia
Oncology
Retrospective Studies
ISSN:2044-5385, 2044-5385
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Summary: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.
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ISSN:2044-5385
2044-5385
DOI:10.1038/s41408-024-01043-5