Background: Adjusted comparisons of the single-arm CARTITUDE-1 clinical trial of ciltacabtagene autoleucel (cilta-cel) and the prospective LocoMMotion study of therapies used in real-world clinical practice (RWCP) have shown the clinical benefits of cilta-cel on response and survival outcomes in patients with triple-class exposed multiple myeloma (TCE-MM). Yet, patients with TCE-MM have a reduced health-related quality of life (HRQoL) compared with age- and sex-matched populations.
Aims: To present adjusted comparisons of patient-reported outcomes (PROs) from TCE-MM patients who received cilta-cel in CARTITUDE-1 vs. RWCP in LocoMMotion.
Methods: EQ-5D-5L, EORTC QLQ-C30 and EORTC QLQ-MY20 questionnaires were administered to all patients in the CARTITUDE-1 Phase 2 and LocoMMotion studies at baseline, day 7, day 28 and every 4 weeks up to 52 weeks. Mixed model repeated measures (MMRM) analyses were performed to analyze changes from baseline (CFB) for each patient cohort and the difference in CFB between cilta-cel and RWCP over time. MMRM models included the baseline PRO score and prognostic characteristics as covariates to balance patient cohorts and to adjust for confounding bias. A sensitivity analysis was implemented assigning worst PRO values to patients who dropped out of the analyses due to death.
Results: A total of 61 patients in CARTITUDE-1 and 202 patients in LocoMMotion had PRO assessments at baseline and during follow-up. At day 7, PRO scores worsened versus baseline in both cohorts, and worsening was more pronounced for cilta-cel in physical, role and social functioning, fatigue and lack of appetite and constipation, coinciding with short term adverse events associated with the cilta-cel infusion and lymphodepleting chemotherapy. From the next assessment at week 4 onwards, PRO values significantly improved over time for cilta-cel patients versus baseline, while improvement from baseline was lower for RWCP for most domains and symptoms. The average improvement versus baseline from week 4 onwards, represented by the absolute difference in CFB between both patient cohorts, was significantly in favor of cilta-cel for Visual Analogue Scale (8.0), Global health status (8.5), pain (-11.4), dyspnea (-8.9), constipation (-8.3), future perspective (16.5) (all p<0.01), emotional functioning (7.4) and feeling restless or agitated (-7.2) (p<0.05) (Table). All other PROs were numerically in favor of cilta-cel across the follow-up period, except for nausea and vomiting and lack of appetite, for which small differences in improvement are numerically in favor of RWCP. The sensitivity analyses assigning worst PRO values to patients who dropped out of the main analyses due to death illustrate that these results are inherently biased against the more effective treatment on survival and underestimate the PRO benefit for cilta-cel.
Image:
Summary/Conclusion: Patients with TCE-MM treated with cilta-cel demonstrated significant improvements vs. RWCP increasing over time in multiple PRO endpoints. These findings indicate that cilta-cel can significantly improve patients’ HRQoL in addition to significant efficacy benefits on response, progression free and overall survival and can help address unmet patient needs.