Cellular and T cell engager Immunotherapy

Category: Cellular and T cell engager Immunotherapy

Quality-adjusted survival analysis of cilta-cel vs standard of care in lenalidomide-refractory multiple myeloma patients who received 1–3 prior lines of therapy: CARTITUDE-4 trial population

(PA-102) Quality-adjusted Survival Analysis of Cilta-cel vs Standard of Care in Lenalidomide-refractory Multiple Myeloma Patients Who Received 1–3 Prior Lines of Therapy: CARTITUDE-4 Trial Population

Friday, September 19, 2025

Surbhi Sidana, MD

Associate Professor
Stanford University School of Medicine

Introduction: In the CARTITUDE-4 trial (NCT04181827), a single ciltacabtagene autoleucel (cilta-cel) infusion significantly improved overall survival and prolonged progression-free survival vs standard of care (SOC) in patients (pts) with lenalidomide-refractory multiple myeloma (MM) with 1–3 prior lines of therapy. Quality-Adjusted Time Without Symptoms or Toxicity Analysis (Q-TWiST) is a validated clinical tool comprehensively integrating progression, survival, treatment toxicities, and pt quality of life (QoL) into a single metric to evaluate overall treatment effect. In this analysis, the Q-TWiST method was applied to evaluate the comprehensive benefit-risk profile of cilta-cel vs SOC using data from the CARTITUDE-4 trial.

Methods: The analysis included the intent-to-treat population from CARTITUDE-4 (N=419), with a maximum follow-up of 45 months. Consistent with Q-TWiST methodology, survival time was divided into 3 distinct health states: 1) time spent without disease progression (PD) and symptoms of toxicity (TWiST), 2) time with toxicity or side effects due to treatment prior to PD (TOX), and 3) time after PD (REL). Grade 3/4 AEs (both treatment-emergent and non‒treatment-emergent) were used to determine TOX; Q-TWiST was computed as a weighted sum of mean time spent in TOX, TWiST, and REL states, where the weights are state-specific QoL utility scores. The base-case model used conventional utility values for each health state: TWiST (1.0), TOX (0.5), and REL (0.5). A 10‒15% relative Q-TWiST gain was considered as a clinically important difference, based on established recommendations (Revicki et al. Qual Life Res. 2006). Sensitivity analyses were conducted to test the robustness of base-case results.

Results: For the base-case, pts treated with cilta-cel showed a significantly longer time without grade 3/4 toxicity compared with pts receiving SOC, with a mean TWiST duration of 26.2 months vs 15.4 months, respectively. The mean TOX was 4.3 months vs 2.4 months, and mean REL was 6.4 months vs 14.3 months. Q-TWiST was significantly longer with cilta-cel by 7.7 months (95% CI, 4.8–10.5, P< 0.001), representing a relative gain of 32.1% compared with SOC. Sensitivity analyses results were consistent with the base-case.

Conclusions: The relative Q-TWiST gain of cilta-cel vs SOC was a statistically significant and clinically meaningful gain in quality and quantity of survival, above the 10–15% threshold criteria generally considered as clinically important in literature, and to our knowledge, one of the highest relative gains to date. Our analysis further supports the favorable benefit-to-risk profile of cilta-cel compared with SOC in pts with lenalidomide-refractory MM as early as after first relapse.