Risk of infections with B-cell maturation antigen-directed immunotherapy in multiple myeloma
Open accessAbstract
B-cell maturation antigen (BCMA) is a novel target for T-cell immunotherapy in multiple myeloma (MM) including bispecific antibody (bsAb), antibody drug conjugates, and chimeric antigen receptor T-cell therapy (CAR-T).1-3 BCMA signaling is critical for survival and proliferation of long-lived plasma cells.4 Impaired immune reconstitution, cytopenia, B-cell aplasia, and hypogammaglobinemia (HGG) can compound preexisting MM-induced immunosuppression.5 In addition, bsAb can redirect and activate regulatory T cells, thus theoretically increasing the risk of infections.6 Here, we describe the infectious complications observed across different BCMA-directed T-cell therapies (bsAb and CAR-T) in relapsed/refractory MM clinical trials at our center.Infections confirmed by clinical, imaging, microbiologic, or histopathologic evidence were captured from day 1 of the first cycle of bsAb and day 1 of lymphodepletion chemotherapy in autologous BCMA CAR-T therapies until disease progression or last follow-up.National Cancer Institute Common Terminology Criteria for Adverse Events, version 5, was used to describe the site and grade of infections.7 The serum immunoglobulin G concentration was evaluated before inception of treatment and approximately monthly thereafter.Antimicrobial prophylaxis was in accordance with institutional standards for CAR-T recipients (supplemental Table 1) and at physician's discretion for patients on bsAb therapy.Descriptive statistics and comparisons were performed using 2-sample t test for continuous variables and x 2 goodness-of-fit test for categorical variables.
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Inhibiting BCMA signaling, which is critical for the survival and proliferation of plasma cells, may worsen the pre-existing myeloma-induced immunosupression.
“Inhibiting BCMA signaling, which is critical for the survival and proliferation of plasma cells, may worsen the pre-existing myeloma-induced immunosupression31,32,34.”
From Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results (2023) · cites this paper as [34]
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- Authors
- Mohan, M., Nagavally, S., Dhakal, B., Radhakrishnan, S. V., Chhabra, S., D’Souza, A., & Hari, P.
- Affiliations
- Medical College of Wisconsin (US)
- Corresponding author
- Mohan, Meera
- ORCID
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2022-04-18
- Volume
- 6
- Issue
- 8
- Pages
- 2466-2470
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC9043928
- OpenAlex
- W4200164765
- Cited by
- 66
- References
- 17
- Citations by year
- 2026: 12 · 2025: 12 · 2024: 15 · 2023: 21 · 2022: 4 · 2013: 1
- FWCI
- 6.53
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc-nd
- Locations
- Blood Advances (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Keywords
- BCMA, multiple myeloma, infection, bispecific antibodies, CAR T-cell therapy, relapsed/refractory multiple myeloma, immunosuppression, lymphodepletion chemotherapy, antibiotic prophylaxis, serum IgG
- MeSH terms
- Receptors, Chimeric Antigen, Humans, Immunologic Factors, Immunotherapy, Multiple Myeloma, B-Cell Maturation Antigen
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