EHA 2025 Insights: CARTITUDE-4 Trial Updates On CAR T in Early R/R MM

Video content above is prompted by the following:

Early detection and intervention in multiple myeloma (MM) relapse have become crucial for optimizing CAR T-cell therapy outcomes, with experts emphasizing the importance of treating biochemical relapse before clinical progression. Regular monitoring through serial laboratory testing (monthly initially, potentially extending to quarterly for long-term remission patients) enables early detection of rising light chains or M-spike elevation. Treatment at biochemical relapse consistently demonstrates superior outcomes compared with waiting for clinical manifestations such as CRAB (calcium elevation, renal dysfunction, anemia, bone lesions) features. This proactive approach is particularly important for CAR T candidates, as maintaining disease control during the manufacturing and bridging period significantly impacts treatment success rates and reduces complications from rapidly progressive disease.

CAR T-cell therapy candidate selection has evolved beyond traditional multiple-relapse settings, with experts advocating for earlier intervention in first-relapse patients, particularly those with high-risk features. Priority candidates include functionally high-risk patients (relapsing within 12-18 months of initial therapy), younger patients (40s-50s age group), and paradoxically, older patients (late 70s) who could benefit from treatment-free intervals without ongoing therapy toxicities. The rationale for early intervention centers on utilizing patients’ autologous T cells while they retain optimal function, before extensive prior therapy exposure compromises immune system integrity. This approach acknowledges that CAR T therapy has achieved remarkable response rates even in heavily pretreated patients, suggesting even greater potential benefits when applied earlier in the disease course.

The decision to proceed with early CAR T therapy requires careful consideration of individual patient factors, disease characteristics, and treatment history. High-priority candidates include patients with cytogenetic high-risk features, those relapsing despite intensive induction regimens including transplant, and patients demonstrating functional high-risk behavior regardless of genetic markers. However, experts maintain some caution regarding universal early adoption due to potential neurologic toxicities that can persist for up to 1 year, requiring careful discussion of risks and benefits. For patients who received only triplet induction therapy without CD38 antibody exposure, consideration should be given to trying quadruplet salvage therapy before proceeding to CAR T, ensuring patients receive optimal conventional therapy before cellular immunotherapy intervention.