Chimeric antigen receptor T cell therapy for myeloma: Where are we now and what is needed to move chimeric antigen receptor T cells forward to earlier lines of therapy? Expert panel opinion from the American Society for Transplantation and Cellular Therapy Guidelines
| Authors: | Anderson, L. D. Jr; Dhakal, B.; Jain, T.; Oluwole, O. O.; Shah, G. L.; Sidana, S.; Perales, M. A.; Pasquini, M. C. |
| Title: | Chimeric antigen receptor T cell therapy for myeloma: Where are we now and what is needed to move chimeric antigen receptor T cells forward to earlier lines of therapy? Expert panel opinion from the American Society for Transplantation and Cellular Therapy |
| Abstract: | Since 2021, 2 B cell maturation antigen (BCMA)-directed chimeric antigen receptor T cell (CAR-T) therapies—idecabtagene vicleucel (ide-cel), and ciltacabtagene autoleucel (cilta-cel)—have been approved by the US Food and Drug Administration (FDA) for treating relapsed or refractory multiple myeloma (RRMM) after 4 or more prior lines of therapy, including an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody. The 2 products have shown unprecedented activity in RRMM, but relapses remain common, and access to and safety of CAR-T therapy in patients with rapidly progressing advanced disease are not ideal. Sequencing CAR-T therapy with other options, including the 2 recently approved BCMA-directed T cell-engaging bispecific antibodies teclistamab and elranatamab, has become increasingly challenging owing to data showing inferior outcomes from CAR-T therapy after prior BCMA-directed therapy. This has led to the consideration of CAR-T therapy earlier in the course of disease for myeloma, when T cells are potentially healthier and the myeloma is less aggressive. To address the question of earlier use of CAR-T therapy, several trials are either ongoing or planned, and results have recently been reported for 2 randomized trials of CAR-T therapy showing improved progression-free survival compared to standard of care therapy in second-line (CARTITUDE-4) or third-line therapy (KarMMA-3). With the anticipation of the FDA possibly expanding approval of CAR-T to earlier lines of myeloma therapy, the American Society for Transplantation and Cellular Therapy convened a group of experts to provide a comprehensive review of the studies that led to the approval of CAR-T therapy in late-line therapy for myeloma, discuss the recently reported and ongoing studies designed to move CAR-T therapy to earlier lines of therapy, and share insights and considerations for sequencing therapy and optimization of patient selection for BCMA-directed therapies in current practice. © 2023 The American Society for Transplantation and Cellular Therapy |
| Keywords: | genetics; multiple myeloma; neoplasm recurrence, local; plasmacytoma; practice guideline; tumor recurrence; chimeric antigen receptor; biological therapy; neoplasms, plasma cell; antibodies, bispecific; bispecific antibody; cellular therapy; humans; human; cell- and tissue-based therapy; b cell maturation antigen; chimeric antigen receptor t cells; b-cell maturation antigen; receptors, chimeric antigen; relapsed/refractory multiple myeloma; t cell-redirection therapy |
| Journal Title: | Transplantation and Cellular Therapy |
| Volume: | 30 |
| Issue: | 1 |
| ISSN: | 2666-6375 |
| Publisher: | Elsevier Inc. |
| Date Published: | 2024-01-01 |
| Start Page: | 17 |
| End Page: | 37 |
| Language: | English |
| DOI: | 10.1016/j.jtct.2023.10.022 |
| PUBMED: | 37913909 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Source: Scopus |
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