Cilta-cel Beats SOC in New Phase 3 Data for Lenalidomide-Refractory Multiple Myeloma


Safety findings were also improved when compared with the previous CARTITUDE-1 study, suggesting the therapy may be better tolerated in earlier lines of therapy.

Ciltacabtagene ciloleucel (cilta-cel; Janssen) yielded higher rates of progression-free survival (PFS) compared with standard of care (SOC) in patients with multiple myeloma (MM) treated in the phase 3 CARTITUDE-4 study (NCT04181827).

New data from the study were presented at the American Society of Clinical Oncology (ASCO) 2023 Annual Meeting, held June 2-6, in Chicago, Illinois, by Binod Dhakal, MD, associate professor, Medical College of Wisconsin.

“In the phase 3 CARTITUDE-4 study, we aimed to test cilta-cel in earlier lines against 2 highly effective SOC regimens in patients with lenalidomide-refractory MM. Widespread early use of lenalidomide has led to a growing lenalidomide refractory population as early as after frontline treatment and this patient population typically has poor outcomes with progression-free survival of less than 12 months,” Dhakal said during his presentation.

CARTITUDE-4 randomized 206 patients to receive cilta-cel and 211 to receive SOC; 176 received cilta-cel as study treatment with 143 continuing to be followed post treatment phase and 77 patients are ongoing with SOC therapy. Patients were randomized between July 2020 and November 2021. The median time from first apheresis to cilta-cel infusion was 79 days and as of November 2022, the median follow-up was 15.9 months (range, 0.2-27). Baseline characteristics were similar between SOC and cilta-cel arms. Around 2/3 of patients had ISS stage 1, 1/3 had only 1 prior line of therapy before screening. Evidence of soft tissue plasmacytomas was seen in 21.2% of cilta-cel patients and 16.6% of SOC patients. Around 60% of patients had cytogenic high riskdisease in both arms.

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Investigators found that patients in the cilta-cel arm had a 12-month PFS rate of 76% compared with 49% in the SOC arm. Cilta-cel improved PFS in patients that had 1 or 2-3 prior lines of treatment. Patients with only 1 prior therapy may have experienced a stronger treatment benefit, but more data are needed to confirm this trend. In the intent-to-treat (ITT) population, cilta-cel yielded an 84.6% overall response rate (ORR) compared with 67.3% with SOC and an 84.7% (95% CI, 78.1-89.4) 12-month duration of response (DOR) rate compared with a 63.0% DOR rate. The median DOR has not been reached in the cilta-cel arm and is 16.6 months (95% CI, 12.9-not estimable) in the SOC arm.

Furthermore, cilta-cel improved rates of overall minimal residual disease (MRD) negativity, with a 60.6% rate in the ITT population and an 87.5% rate in the overall evaluable population compared with a 15.6% rate in the ITT population and a 32.7% rate in the evaluable population treated with SOC. Overall survival is still immature but the calculated hazard rate (HR) is 0.78 (95% CI, 0.5-1.2; P = .26) in the cilta-cel arm compared with the SOC arm. The as-treated population had a 99% ORR, an 86% complete response rate, a 72% MRD negativity rate at 10-5, and a 90% PFS rate at 12 months after apheresis.

Dhakal and colleagues compared data from CARTITUDE-4 against that seen in the phase 1/2 CARTITUDE-1 study (NCT03548207) and found that PFS, CR, and MRD negativity rates were all higher in the phase 3 study. He noted that the safety profile was similar across studies evaluating cilta-cel, but with lower rates of neurotoxicity when compared with CARTITUDE-1.

“Compared to SOC, cilta-cel significantly extended PFS in patients with lenalidomide-refractory MM after 1-2 prior lines of therapy... this is the best HR ever reported in this patient population in a randomized, controlled setting,” Dhakal said. “Use of cilta-cel in early lines may lead to improved tolerability.Overall, cilta-cel has the potential to be a new SOC for patients with lenalidomide-refractory MM after first relapse.”

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Dhakal B, Yong K, Harrison SJ, et al. First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. Presented at: ASCO 2023 Annual Meeting; June 2-6; Chicago, Illinois. Abstract #LBA106
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