Cilta-Cel Delivers Sustained Survival Benefits Across Genetic Risk Profiles in MM

With a single infusion of ciltacabtagene autoleucel (cilta-cel), significant improvements in progression-free survival (PFS) and overall survival (OS) were achieved in patients with lenalidomide-refractory multiple myeloma (MM) in the primary analysis of CARTITUDE-4. Results from the subgroup analysis from the intention-to-treat population of the study reveal similar efficacy.

At the 2025 ASCO Annual Meeting, Surbhi Sidana, MD, associate professor of Medicine at Stanford University, presented the findings from patients with high-risk cytogenetics in a poster session. Results showed improvement in PFS and OS with cilta-cel compared to the standard of care in all assessed subgroups, including patients with extramedullary disease (EMD) and pLOT.

“Subgroup analyses from the CARTITUDE-4 trial demonstrate that cilta-cel provides sustained benefit in earlier lines of therapy across various patient subgroups, including those with high-risk disease,” Binod Dhakal, MD, a CARTITUDE-4 investigator and associate professor, Division of Hematology and Oncology, Department of Medicine, Medical College of Wisconsin told Blood Cancers Today.

“Median progression-free survival [PFS] was not reached [NR] in standard-risk patients and was 37 months and 30 months in patients with high-risk and at least two high-risk cytogenetic abnormalities, respectively. These are highly impressive results and should inform clinical decision-making on the use of cilta-cel in earlier lines,” he said.

At a median follow-up of 33.6 months, the median PFS among patients with EMD was 13 months with cilta-cel versus 4 months with SOC (HR, 0.71; 95% CI, 0.34–1.49), and the median OS was NR with cilta-cel compared with 16 months in the SOC arm (HR, 0.61; 95% CI, 0.26–1.47).

“In CARTITUDE-4, patients with EMD derived greater benefit from cilta-cel compared to standard of care. However, this subgroup remains a significant unmet clinical need, as the median PFS was limited to approximately 13 months, said Dr. Dhakal. “Further investigation into the underlying biology of EMD is warranted to identify additional therapeutic strategies that may enhance outcomes when combined with cilta-cel.”

Among patients with one pLOT, the median PFS was NR with cilta-cel versus 17 months with SOC (HR, 0.4; 95% CI, 0.25–0.67). The median OS was also NR among patients treated with cilta-cel, compared with NR (HR, 0.56; 95% CI, 0.28–1.11) in the SOC arm.

Overall, cilta-cel appears to have a positive benefit-risk ratio in patients with lenalidomide-refractory MM, according to the study investigators. Looking forward, investigators plan to expand on the knowledge gained from this analysis.

“We plan to continue longitudinal follow-up of patients in the cilta-cel arm to identify clinical and biological factors associated with durable responses. While retreatment or sequencing strategies following initial response are not currently planned within the cilta-cel arm, patients in the SOC arm will have the opportunity to receive cilta-cel. Given the profound efficacy observed with cilta-cel in earlier lines of therapy, this crossover represents a critical opportunity for SOC patients to access a highly effective treatment option,” said Dr. Dhakal.