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Expert Insights On An Evolving Treatment Landscape In Multiple Myeloma: Updates From EHA 2025 - Episode 7

Identifying The Ideal Candidate for CAR T in Late R/R Multiple Myeloma

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Panelists discuss how age should not be a barrier to chimeric antigen receptor (CAR) T therapy, emphasizing that organ function and disease control during bridging are more important factors, while acknowledging system-based capacity limitations for widespread CAR T implementation.

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    The CARTITUDE-4 trial subgroup analysis reveals exceptional benefits of CAR T-cell therapy in high-risk multiple myeloma populations, with median follow-up of 34 months demonstrating sustained efficacy advantages. In patients with cytogenetic abnormalities, including deletion 17p and t(4;14), the standard-of-care arm achieved median progression-free survival (PFS) of only 7 to 10 months, whereas the CAR T arm extended this to approximately four times longer. Most remarkably, patients with extramedullary disease showed a median PFS of only 4 months with standard therapy compared with 13 months with CAR T, representing more than triple the treatment benefit. These findings strongly support prioritizing CAR T therapy for highest-risk patient populations where conventional therapy options provide limited durability.

    Analysis across different lines of therapy reveals that CAR T-cell therapy maintains consistent benefit regardless of treatment sequence, challenging traditional paradigms of reserving cellular therapy for late-stage disease. Although standard care shows expected attrition with each subsequent line of therapy (17 months for second line, declining to 8 months for third line), CAR T therapy maintained median PFS that was not reached across all lines evaluated. This consistency suggests that line of therapy may be less important than patient and disease characteristics in determining CAR T benefit. The data support earlier integration of CAR T therapy, particularly for patients with high-risk features, rather than adhering to strict sequential treatment algorithms that may compromise patient outcomes through delayed intervention.

    Expert consensus strongly challenges age-based restrictions for CAR T-cell therapy, with successful treatment reported in patients up to 89 years old, emphasizing functional status over chronological age. The ideal CAR T candidate is defined more by organ function, support system availability, and geographic accessibility than by traditional eligibility criteria. Patients must be able to remain near the treatment center for approximately 1 month and have adequate support systems to manage potential complications. Key exclusions include active central nervous system involvement and rapidly progressive disease that cannot be controlled during the manufacturing period. The critical limitation identified is system-based capacity constraints, with most transplant centers able to provide CAR T therapy to only 20% to 30% of potentially eligible patients, necessitating careful prioritization of highest-risk patients who would derive the greatest benefit from this limited but highly effective therapeutic resource.

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