Clinical Report: Infectious Complications in BCMA-Targeted Multiple Myeloma Therapies
Overview
This retrospective study evaluated infectious complications in 256 patients with relapsed/refractory multiple myeloma treated with BCMA-targeted therapies, including CAR-T, bispecific antibodies (BsAb), and antibody drug conjugates (ADC). The analysis revealed differences in infection incidence, risk factors, and timing among these treatment modalities, highlighting the need for tailored infection management strategies.
Background
BCMA-targeted therapies, such as CAR-T, BsAb, and ADC, have transformed treatment options for relapsed/refractory multiple myeloma by targeting plasma cells. Despite high response rates, these therapies are associated with infectious complications, particularly in a population already vulnerable due to disease and prior treatments. Understanding the incidence, nature, and risk factors of infections is critical to optimizing patient outcomes and guiding therapy selection. This study compares infectious events across BCMA-targeted modalities to inform clinical practice.
Data Highlights
Characteristic
CAR-T (n=92)
BsAb (n=55)
ADC (n=109)
Median Age (years)
62 (IQR 56−69)
65 (IQR 58−72)
Not specified
Median Prior Lines of Therapy
7 (IQR 5−8)
6 (IQR 4−9)
Not specified
Clinical Trial Participation (%)
57%
56%
18%
Key Findings
Severe (grade ≥3) infections were the primary endpoint, with incidence compared across CAR-T, BsAb, and ADC therapies.
Patients receiving CAR-T had a median age of 62 years and a higher median number of prior therapies compared to BsAb recipients.
Infection risk was analyzed in relation to baseline factors including neutropenia, lymphopenia, hypogammaglobulinemia, and prior BCMA therapy.
Periods of neutropenia and hypogammaglobulinemia post-treatment were significant time-dependent covariates influencing infection risk.
Prophylactic antimicrobial use followed institutional guidelines, and cytokine release syndrome without infection was excluded from infectious event counts.
Statistical models adjusted for competing risks and patient-specific factors to robustly assess infection incidence and rates over time.
Clinical Implications
Clinicians should closely monitor for severe infections in patients receiving BCMA-targeted therapies, especially CAR-T and BsAb, given their immunosuppressive effects and associated neutropenia and hypogammaglobulinemia. Tailored infection prophylaxis and timely management of immunologic deficits may reduce infectious morbidity. Understanding individual patient risk factors can guide therapy selection and supportive care strategies.
Conclusion
BCMA-targeted therapies for relapsed/refractory multiple myeloma carry distinct infectious risks influenced by patient and treatment factors. Comprehensive infection risk assessment and mitigation are essential to optimize outcomes in this vulnerable population.
References
BCMA-Targeted Therapies in Multiple Myeloma, 2023 -- Overview of Treatment Modalities
Infectious Complications with T-cell Redirecting Therapies, 2023 -- Emerging Clinical Data
FDA Approvals of BCMA-Targeted Agents, 2022-2023 -- Regulatory Updates
Memorial Sloan Kettering Cancer Center Study, 2023 -- Retrospective Analysis of BCMA Therapies
by 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. Giralt, Saad Z. Usmani, Zainab Shahid, Sham Mailankody, Alexander M. Lesokhin
