TY - JOUR
T1 - Chimeric Antigen Receptor T Cell Therapy for Myeloma
T2 - 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
AU - Anderson, Larry D.
AU - Dhakal, Binod
AU - Jain, Tania
AU - Oluwole, Olalekan O.
AU - Shah, Gunjan L.
AU - Sidana, Surbhi
AU - Perales, Miguel Angel
AU - Pasquini, Marcelo C.
N1 - Publisher Copyright:
© 2023 The American Society for Transplantation and Cellular Therapy
PY - 2024/1
Y1 - 2024/1
N2 - 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.
AB - 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.
KW - B cell maturation antigen
KW - Cellular therapy
KW - Chimeric antigen receptor T cells
KW - Relapsed/refractory multiple myeloma
KW - T cell-redirection therapy
UR - http://www.scopus.com/inward/record.url?scp=85179661316&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85179661316&partnerID=8YFLogxK
U2 - 10.1016/j.jtct.2023.10.022
DO - 10.1016/j.jtct.2023.10.022
M3 - Article
C2 - 37913909
AN - SCOPUS:85179661316
SN - 2666-6375
VL - 30
SP - 17
EP - 37
JO - Transplantation and Cellular Therapy
JF - Transplantation and Cellular Therapy
IS - 1
ER -