Infectious complications in patients with relapsed refractory multiple myeloma after BCMA CAR T-cell therapy
Open accessAbstract
B-cell maturation antigen-targeted chimeric antigen receptor T-cell therapy (BCMA CAR-T) is an effective treatment of relapsed refractory multiple myeloma (MM). However, the pattern of infectious complications is not well elucidated. We performed a single-center retrospective analysis of infection outcomes up to 1 year after BCMA CAR-T for MM from 2018 to 2020. Fifty-five patients with MM were treated with BCMA CAR-T. Before lymphodepletion (LD), 35% of patients had severe hypogammaglobulinemia and 18% had severe lymphopenia. Most patients (68%) received bridging chemotherapy (BC) before LD. In the first month after CAR-T, 98% patients had grade 3 to 4 neutropenia. At 1 year after infusion, 76% patients had hypogammaglobulinemia. With a median follow-up of 6.0 months (95% confidence interval, 4.7-7.4), there were a total of 47 infection events in 29 (53%) patients: 40% bacterial, 53% viral, and 6% fungal. Most (92%) were mild-moderate and of the lower/upper respiratory tract system (68%). Half of the infections (53%) occurred in the first 100 days after CAR-T infusion. Although no statistically significant risk factors for infection were identified, prior lines of therapy, use of BC, recent infections, and post–CAR-T lymphopenia were identified as possible risk factors that need to be further explored. This is the largest study to date to assess infectious complications after BCMA CAR-T. Despite multiple risk factors for severe immunosuppression in this cohort, relatively few life-threatening or severe infections occurred. Further larger studies are needed to better characterize the risk factors for and occurrence of infections after BCMA CAR-T.
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BCMA-targeted T-cell-redirecting therapies have been linked to a heightened susceptibility to infectious complications due to their mechanism of action.
“BCMA-targeted T-cell-redirecting therapies have been linked to a heightened susceptibility to infectious complications due to their mechanism of action30–33.”
From Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results (2023) · cites this paper as [32]
The Abstract reports infections in 29 of 55 patients after BCMA CAR-T, and the Introduction lists infections among CAR-T-associated toxicities. But the study concerns BCMA CAR-T specifically, not all BCMA-targeted T-cell-redirecting therapies, and it does not establish that their mechanism of action caused heightened infection susceptibility. Page numbers were not available in our copy. (LLM, conf=0.86)
Experimental — accuracy not yet measuredInhibiting 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 [32]
The Introduction identifies hypogammaglobulinemia and infections as CAR-T toxicities, and the Results report hypogammaglobulinemia both before and after BCMA CAR-T. However, the paper does not say that BCMA signaling is critical for plasma-cell survival and proliferation or that inhibiting that signaling worsens pre-existing myeloma-induced immunosuppression. (LLM, conf=0.82)
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Cited by
Sorted by citations
Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results
Lesokhin, A. M., Tomasson, M. H., Arnulf, B., Bahlis, N. J., Miles Prince, H., Niesvizky, R., Rodrίguez-Otero, P., Martinez-Lopez, J., Koehne, G., Touzeau, C., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02528-9 · Cited by 664 · see citing works
Lancman, G., Parsa, K., Kotlarz, K., Avery, L., Lurie, A., Lieberman-Cribbin, A., Cho, H. J., Parekh, S. S., Richard, S., Richter, J., et al. (2023) · Blood Cancer Discovery · doi:10.1158/2643-3230.bcd-23-0049 · Cited by 140 · see citing works
- Authors
- Thiruvengadam, S. K., Sheng, Y., Huang, C.-Y., Bylsma, S., Lo, M., Kennedy, V., Natsuhara, K., Martin, T., Wolf, J., Shah, N., & Wong, S. W.
- Affiliations
- 1Division of Hematology/Oncology, Department of Medicine
- 3Department of Epidemiology and Biostatistics
- University of California, San Francisco (US)
- 4Department of Pharmacy
- University of California San Francisco Medical Center (US)
- ORCID
- Venue
- Blood Advances
- Publisher
- American Society of Hematology
- Published
- 2021-09-20
- Volume
- 6
- Issue
- 7
- Pages
- 2045-2054
- ISSN
- 2473-9529 (ISSN-L)
- 2473-9537
- PMC
- PMC9006279
- OpenAlex
- W3201110970
- Cited by
- 131
- References
- 2
- Citations by year
- 2026: 19 · 2025: 24 · 2024: 40 · 2023: 37 · 2022: 9 · 2013: 1
- FWCI
- 7.83
- 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)
- eScholarship (California Digital Library) (submittedVersion)
- Topics
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Health Sciences › Medicine › Hematology › Multiple Myeloma Research and Treatments
- Health Sciences › Medicine › Oncology › Neutropenia and Cancer Infections
- Keywords
- BCMA CAR T-cell therapy, relapsed/refractory multiple myeloma, infectious complications, hypogammaglobulinemia, lymphopenia, neutropenia, lymphocyte depletion, respiratory infections, viral infection, bacterial infection, fungal infection, immunosuppression, risk factors
- MeSH terms
- Receptors, Chimeric Antigen, Humans, Multiple Myeloma, Retrospective Studies, Immunotherapy, Adoptive, B-Cell Maturation Antigen
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