Abstract
Contributing Factors of Manufacturing Failure for BCMA CAR-T Cell Products in Multiple Myeloma
Transplantation and cellular therapy, Vol.31(2 Supplement), pp.S414-S414
02/2025
DOI: 10.1016/j.jtct.2025.01.634
Abstract
B-cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) therapies are important treatments in relapsed refractory multiple myeloma. CAR-T manufacturing failure is one obstacle to access for patients. Exposure to prior anti-myeloma therapies may influence patients’ T cells subsequently limiting their ability to manufacture CAR-T cells, although there is a paucity of data to guide the best wash-out periods.
Patients at two academic medical centers who underwent apheresis for idecabtagene vicleucel (ide-cel) or ciltacabtagene autoleucel (cilta-cel) manufacturing between 2021 to 2024 were identified and included. CAR-T cell products that were out of specification for commercial use but released under expanded access protocol were included in manufacturing successes. Electronic medical records were retrospectively reviewed for any prior exposure and time from exposure to apheresis to alkylating agents, autologous transplantation, and anti-BCl2 agents. Additionally, the line of therapy immediately prior to apheresis, time from exposure until apheresis of proteosome inhibitors (PIs), immunomodulatory agents (IMIDs), anti-CD38 antibodies, or corticosteroids, were assessed.
In total, 43 patients undergoing apheresis for ide-cel (n=30) or cilta-cel (n=13) were included, of whom 8 patients had manufacturing failure. Too few patients had prior exposure to prior anti-BCMA therapies or bispecific antibody therapies for analysis. Agents in the immediate prior treatment line were PI (n=16), IMID (n=18), anti-CD38 antibody (n=13), corticosteroids (n=33), selinexor (n=8). The median time of exposure to agents in the prior line of therapy is shown in Figure 1. For patients ever exposed to alkylating agents, the median months since exposure was 41.1 (range 0.9 to 139 months). Time since exposure to PIs, IMIDs, anti-CD38 antibodies or selinxor was not associated with odds of manufacturing failure. Prior exposure to any alkylating agent was associated with lower odds of manufacturing failure (0.93, 95% CI 0.87-0.98, p<0.01) (Figure 2). No baseline patient characteristics were associated with manufacturing failure.
More time from exposure to alkylating agents was associated with increased odds of manufacturing success. No significant association was identified between the time since exposure to PIs, IMIDs, anti-CD38 antibodies, or selinexor and manufacturing failure, though the rarity of manufacturing failures limits this study's power. A larger multicenter analysis is needed to assess the influence of newer agents, such as bispecific antibodies, on manufacturing failure rates.
Details
- Title: Subtitle
- Contributing Factors of Manufacturing Failure for BCMA CAR-T Cell Products in Multiple Myeloma
- Creators
- Samantha Sparrow - University of Iowa, Iowa City, IAAllyson Wolcott - University of Iowa Healthcare, Iowa City, IASarah Mott - University of IowaJames McCollough - University of IowaJames Davis - Medical University of South CarolinaHira Shaikh - University of IowaChristopher Sun Strouse - US Myeloma Innovations Research Collaborative (USMIRC), Westwood, KS
- Resource Type
- Abstract
- Publication Details
- Transplantation and cellular therapy, Vol.31(2 Supplement), pp.S414-S414
- Publisher
- Elsevier Inc
- DOI
- 10.1016/j.jtct.2025.01.634
- ISSN
- 2666-6367
- eISSN
- 2666-6367
- Language
- English
- Date published
- 02/2025
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984795477102771
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