Key Findings From the CARTITUDE-4 Trial of Cilta-Cel in Multiple Myeloma

EP: 1.Overview of the CARTITUDE-4 Trial: Cilta-Cel in Multiple Myeloma

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EP: 2.Key Findings From the CARTITUDE-4 Trial of Cilta-Cel in Multiple Myeloma

EP: 3.Evaluating Cilta-Cel’s Efficacy in the CARTITUDE-4 Trial

EP: 4.Key Takeaways From the CARTITUDE-4 Trial in Multiple Myeloma

Binod Dhakal, MD, MS, assistant professor of medicine in the Division of Hematology and Oncology at the Medical College of Wisconsin, discusses the safety and efficacy findings from the CARTITUDE-4 trial (NCT04181827).

CARTITUDE-4 is a phase 3, randomized study evaluating treatment with the chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel; Carvykti) in patients with lenalidomide (Revlimid)-refractory multiple myeloma who had received at least 1 prior line of therapy.

Updated results were presented at the 2024 International Myeloma Society Annual Meeting, showing that cilta-cel reduced the risk of death by 45% vs standard of care (SOC) in this patient population. At a median follow-up of 33.6 months (range, 0.1-45.0), cilta-cel led to a 30-month overall survival (OS) rate of 76.4% vs 63.8% with SOC (HR, 0.55; 95% CI, 0.39-0.79; P = .0009), which consisted of physician’s choice of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone, or daratumumab (Darzalex) plus pomalidomide and dexamethasone.

Transcription:

0:09 | In the study, a total of 419 patients were randomized, cilta-cel patients were 208 and standard of care was 211. In this updated follow-up at 33.6 months, we observed significant benefit with cilta-cel in terms of overall survival compared [with] standard of care, with the hazard ratio of .55. The median overall survival was not reached with cilta-cel or the standard of care, and the 30-month overall survival rates were 76% with cilta-cel vs 64% in the standard of care arm.

0:45 | Importantly, this overall survival benefit [was in] all the previously specified subgroups, including the patients with high-risk cytogenetics, whose extremity of disease is stage III. In terms of progression-free survival at a 15 month follow-up, the median progression-free survival was not reached in the cilta-cel arm, and was 11.8 months in the standard of care arm, and at this longer follow-up, the median progression-free survival was still not reached in the cilta-cel arm, and was 11.8 months in the standard of care arm, with the hazard ratio of .29. The median time to symptom worsening was also not reached with cilta-cel and was 34.3 months with the standard of care arm.

1:27 | Safety was consistent with the previous interim analysis, with no new safety signal in terms of delayed neurotoxicity. Deaths occurred in 50 and 82 patients in the cilta-cel and standard of care groups, respectively, and 21 and 51 died due to progressive disease.

1:46 | In summary, this longer follow-up at 33.6 months shows that cilta-cel significantly reduces the risk of death and delayed symptom worsening or standard of care in patients with lenalidomide-refractory multiple myeloma as early as first relapse. This is the first study in multiple myeloma where CAR T has shown significant survival benefit compared [with] standard of care in patients.

REFERENCE:

Mateos M-V, San-Miguel J, Dhakal, et al. Overall survival (OS) with ciltacabtagene autoleucel (Cilta-cel) versus standard of care (SoC) in lenalidomide (Len)-refractory multiple myeloma (MM): Phase 3 CARTITUDE-4 study update. Presented at: 2024 International Myeloma Society Annual Meeting; September 25-28, 2024; Rio de Janeiro, Brazil. Abstract OA – 65.