Safety and efficacy of BCMA-directed chimeric antigen receptor T-cell therapy for the treatment of plasma cell leukemia
Despite significant therapeutic advances in multiple myeloma (MM), outcomes in patients with plasma cell leukemia (PCL) remain dismal. We conducted a multicenter retrospective analysis of patients with PCL who were treated with the B-cell maturation antigen-directed chimeric antigen receptor T-cell (CAR-T) products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). We identified 34 patients; 19 patients received ide-cel and 15 received cilta-cel. With a median follow-up of 11.9 months, the overall median progression-free survival (mPFS) was 9.0 months (95% confidence interval [CI], 4-15) and the median overall survival (mOS) was 13.0 months (95% CI, 8 to not estimable [NE]). The 1-year cumulative incidence of progression or death was 72%, and the 1-year cumulative incidence of death was 47%. Patients who received cilta-cel had a longer mPFS (19.0 months vs 6.0 months) and mOS (>23 months [NE] vs 9.0 months) when compared with those treated with ide-cel. Similarly, the 1-year cumulative incidence of disease progression or death was 37.5% (95% CI, 17.4-68.5) with cilta-cel, whereas all patients treated with ide-cel progressed or died within 12 months of infusion. The rates of hematologic and nonhematologic toxicities were similar between patients treated with cilta-cel and those treated with ide-cel and were consistent with those reported in patients with MM. In this first multicenter study that evaluated patients with PCL who were treated with standard-of-care CAR-T products, we show that CAR-T is safe, feasible, and associated with improved outcomes when compared with historic standards.
Authors
- Jack Khouri (ORCID: https://orcid.org/0000-0002-2473-6528)
- Mahmoud Gaballa (ORCID: https://orcid.org/0000-0002-3928-6590)
- Hamza Hashmi (ORCID: https://orcid.org/0000-0002-4129-5867)
- Aimaz Afrough (ORCID: https://orcid.org/0000-0003-2645-8557)
- Surbhi Sidana (ORCID: https://orcid.org/0000-0003-3288-7614)
- Hashim Mann (ORCID: https://orcid.org/0000-0002-8961-6228)
- Danai Dima (ORCID: https://orcid.org/0000-0002-3587-7975)
- William Clark (ORCID: https://orcid.org/0009-0004-5498-0654)
- Yi Lin
- Gliceida Galarza Fortuna (ORCID: https://orcid.org/0000-0002-1084-953X)
- Denise L. Pereira (ORCID: https://orcid.org/0000-0002-1992-7899)
- Amer Beitinjaneh (ORCID: https://orcid.org/0000-0002-1661-5865)
- Larry D. Anderson (ORCID: https://orcid.org/0000-0002-6531-9595)
- Leyla Shune (ORCID: https://orcid.org/0000-0003-1650-1873)
- Shebli Atrash (ORCID: https://orcid.org/0000-0003-4547-7534)
- Shambavi Richard (ORCID: https://orcid.org/0000-0003-0274-4292)
- Vanna Hovanky
- Peter A. Forsberg (ORCID: https://orcid.org/0000-0003-3248-7530)
- Adriana Rossi (ORCID: https://orcid.org/0009-0004-9914-5628)
- Doris K. Hansen (ORCID: https://orcid.org/0000-0002-9813-3578)
- Gabe De Avila
- Joseph P. McGuirk (ORCID: https://orcid.org/0000-0002-0539-4796)
- Douglas W. Sborov (ORCID: https://orcid.org/0000-0003-4268-2698)
- Mehmet H. Kocoglu (ORCID: https://orcid.org/0000-0002-9888-5737)
- Amandeep Godara (ORCID: https://orcid.org/0000-0003-1943-4442)
- Elena Nazarenko (ORCID: https://orcid.org/0000-0001-6880-525X)
- Binod Dhakal (ORCID: https://orcid.org/0000-0002-4377-9742)
- Sneha Purvey (ORCID: https://orcid.org/0000-0001-8349-2220)
- Krina K. Patel (ORCID: https://orcid.org/0000-0002-8894-027X)
- Myo Htut
- Peter Michael Voorhees (ORCID: https://orcid.org/0000-0003-1661-718X)
- Megan M. Herr (ORCID: https://orcid.org/0000-0001-5768-9396)
- Christopher J. Ferreri (ORCID: https://orcid.org/0000-0003-2997-4856)
- Lauren Cole Peres (ORCID: https://orcid.org/0000-0002-6620-8600)
- James A. Davis (ORCID: https://orcid.org/0000-0001-7978-1652)
- Andre De Menezes Silva Corraes (ORCID: https://orcid.org/0009-0001-8234-6755)
Institutions
- University of Maryland, Baltimore (US)
- Roswell Park Comprehensive Cancer Center (US)
- City Of Hope National Medical Center (US)
- Cleveland Clinic (US)
- Mayo Clinic (US)
- Memorial Sloan Kettering Cancer Center (US)
- The University of Texas MD Anderson Cancer Center (US)
- University of Miami (US)
- University of Kansas (US)
- Medical University of South Carolina (US)
- Palo Alto University (US)
- Virginia Commonwealth University (US)
- Medical College of Wisconsin (US)
- University of Utah (US)
- Huntsman Cancer Institute (US)
- University of Washington Medical Center (US)
- Moffitt Cancer Center (US)
- Fred Hutch Cancer Center (US)
- Southwestern Medical Center (US)
- The University of Kansas Cancer Center (US)
- Levine Cancer Institute (US)
- University of Miami Health System (US)
- City of Hope (US)
- Tisch Hospital (US)
- University of Colorado Cancer Center (US)
- Stanford Medicine (US)
- Cellular Therapeutics (United Kingdom) (GB)
- Mayo Clinic in Florida (US)
- Sidney Kimmel Comprehensive Cancer Center (US)
- U-M Rogel Cancer Center (US)
- Wake Forest University (US)
- University of Colorado Anschutz Medical Campus (US)
- The University of Texas Southwestern Medical Center (US)
- University of Colorado Denver (US)
- Stanford University (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- Blood Advances
- Published
- 2025-08-28
- DOI
- https://doi.org/10.1182/bloodadvances.2025016966
- Citations
- 3
- Primary Topic
- CAR-T cell therapy research
- Type
- article
- Field-Weighted Citation Impact
- 3.14
Funders
- Bristol-Myers Squibb
- Pfizer
- AstraZeneca
- GlaxoSmithKline
- Sanofi
- Gilead Sciences
- Regeneron Pharmaceuticals
- Prothena
- Adaptive Biotechnologies
- BeiGene
- Genentech
- Legend Biotech