Breaking Down CARTITUDE-4: Survival in High-Risk Patients, Extramedullary Disease, and Prior 1 to 3 Lines of Therapy

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The CARTITUDE-4 study demonstrated significant progression-free survival (PFS) advantages for cilta-cel across multiple high-risk subgroups with a 33.6-month median follow-up. The randomized phase 3 trial compared cilta-cel with standard of care (daratumumab-pomalidomide-dexamethasone or pomalidomide-bortezomib-dexamethasone) in patients who are lenalidomide-refractorywith 1 to 3 prior lines of therapy. Both standard-risk and high-risk cytogenetic patients showed substantial benefits with HRs of 0.43 and 0.38, respectively.

Individual high-risk cytogenetic abnormalities, including deletion 17p, t(4;14), and 1q21 amplification, all showed favorable outcomes with cilta-cel, even in patients with multiple high-risk features. The therapy appears to partially overcome poor prognostic cytogenetic markers, with overall survival benefits observed across cytogenetic risk groups. Patients with extramedullary disease, while having shorter PFS, still significantly outperformed standard of care with 13 months vs 4 months median PFS.

Analysis by prior lines of therapy revealed consistent advantages regardless of treatment history, with particularly impressive results in standard-risk patients with only one prior line of therapy. The PFS curves in this subgroup suggest the possibility of functional cure or extremely durable remissions lasting many years. These findings support the use of cilta-cel across diverse patient populations, including those traditionally considered high-risk for poor outcomes.