Subgroup data from CARTITUDE-4 suggest that cilta-cel may overcome the poor prognosis associated with some high-risk features in multiple myeloma.
“Compared with SOC, cilta-cel improved PFS and OS in patients with high-risk cytogenetics, suggesting it may overcome the poor prognosis associated with these high-risk features,” according to study author Surbhi Sidana, MD.
Progression-free survival (PFS) and overall survival (OS) improved among subgroups of patients with relapsed/refractory multiple myeloma who received ciltacabtagene autoleucel (cilta-cel; Carvykti), according to subgroup analysis findings from the phase 3 CARTITUDE-4 study (NCT04181827) presented in a poster session at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.1
Data showed that in those with high-risk cytogenetics—defined as del(17p), t(4;14), t(14;16), or gain/amp(1q) via fluorescence in situ hybridization—the CAR T-cell therapy (n = 123) led to a median PFS of 37.1 months (95% CI, 26.7-not evaluable [NE]) vs 10.3 months (95% CI, 7.6-12.6) with SOC (n = 132); the median OS in the respective arms was not reached (NR; 95% CI, NE-NE) and 38.0 months (95% CI, 34.0-NE). In those with standard-risk cytogenetics, cilta-cel (n = 69) led to a median PFS that was NR (95% CI, NE-NE) and a median OS that was also NR (95% CI, NE-NE); SOC (n = 70) led to a median PFS of 20.6 months (95% CI, 11.2-33.6) and a median OS that was NR (95% CI, 34.7-NE).
Within the group of patients with EMD, those who received cilta-cel (n = 21) experienced a median PFS of 12.6 months (95% CI, 1.2-18.4) vs 4.0 months (95% CI, 2.8-8.4) with SOC (n = 18); the median OS was NR (95% CI, 3.8-NE) with the CAR T-cell therapy vs 15.7 months (95% CI, 8.8-NE) with SOC. In patients without EMD, those given cilta-cel (n = 187) experienced a median PFS that was NR (95% CI, 37.1-NE) vs 12.2 months (95% CI, 10.3-14.8) with SOC (n = 193); the median OS in the respective arms was NR (95% CI, NE-NE) and NR (95% CI, 37.8-NE).
A significant improvement in PFS and OS was observed with cilta-cel over SOC in each subgroup of prior line of therapy. In those who only received 1 prior line, cilta-cel (n = 68) led to a median OS that was NR (95% CI, 27.8-NE) vs 17.4 months (95% CI, 11.1-26.7) with SOC (n = 68); the median OS with the respective treatments was NR (95% CI, NE-NE) and NR (95% CI, 37.8-NE). In those who received 2 prior lines of therapy, the median PFS with cilta-cel (n = 83) was NR (95% CI, 25.9-NE) vs 12.2 months (95% CI, 7.5-14.0) with SOC (n = 87); the median OS with the respective approaches was NR (95% CI, NE-NE) and NR (95% CI, NE-NE). In those who received 3 prior lines, the median PFS with cilta-cel (n = 57) was also NR (95% CI, 29.1-NE) vs 7.6 months (95% CI, 3.8-10.7) with SOC (n = 56); the median OS in the respective arms was NR (95% CI, NE-NE) and 34.0 months (95% CI, 19.9-NE).
“These data continue to support a positive benefit-risk ratio for cilta-cel in patients with lenalidomide [Revlimid]-refractory multiple myeloma as early as after first relapse,” Surbhi Sidana, MD, of Stanford University School of Medicine, in Stanford, California, and colleagues, wrote in the poster.
The open-label trial enrolled patients with relapsed/refractory multiple myeloma whose tumors were resistant to lenalidomide and who had received 1 to 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug.2 Patients had an ECOG performance status no higher than 1, and had not received prior CAR T-cell therapy or BCMA-targeted therapy.
Participants were randomly assigned 1:1 to receive SOC (n = 211), which was physician’s choice of pomalidomide (Pomalyst), bortezomib (Velcade), and dexamethasone (PVd) or daratumumab (Darzalex), pomalidomide, and dexamethasone (DPd), or a single infusion of cilta-cel post-physician’s choice of bridging therapy with PVd or DPd (n = 208). They were stratified by bridging therapy selection (PVd vs DPd), severity of disease at screening (I vs II vs III), and number of prior therapies received (1 vs 2 vs 3).
At a median follow-up of 15.9 months (range, 0.1-27.3), prior data from the study showed that the median PFS with cilta-cel was NR vs 11.8 months (95% CI, 9.7-13.8) with SOC (HR, 0.26; 95% CI, 0.18-0.38; P < .001). These data supported the April 2024 FDA approval of the CAR T-cell therapy for use in adult patients with relapsed or refractory multiple myeloma who have received at least 1 prior therapy, including a PI and an IMiD, and who are lenalidomide refractory.3
At a median follow-up of 33.6 months (range, 0.1-45.0), the hazard ratios for PFS and OS were 0.29 (95% CI, 0.22-0.39; P < .0001) and 0.55 (95% CI, 0.39-0.79; P = .0009), respectively, demonstrating a significant improvement with cilta-cel vs SOC.4 Moreover, the CAR T-cell therapy led to a higher overall minimal residual disease (MRD)–negative complete response or better (≥CR) rate vs SOC, at 82.1% vs 25.2%, and a higher sustained MRD-negative ≥CR rate vs SOC, at 51.7% vs 9.7%.5
Within those who had high-risk cytogenetics, those with del(17p) who received cilta-cel (n = 49) experienced a median PFS of 29.9 months (95% CI, 13.4-NE) vs 8.7 months (95% CI, 5.1-14.0) with SOC (n = 43); the median OS with the respective treatments was NR (95% CI, NE-NE) and NR (95% CI, 17.3-NE).1 In those with t(4;14), cilta-cel (n = 30) led to a median PFS of 37.1 months (95% CI, 18.0-NE) vs 6.7 months (95% CI, 3.8-13.7) with SOC (n = 30); the median OS with the respective approaches was NR (95% CI, NE-NE) and 26.8 months (95% CI, 20.3-NE).
Moreover, in those with gain/amp(1q), the median PFS with cilta-cel (n = 89) was 37.1 months (95% CI, 25.9-NE) vs 10.3 months (95% CI, 7.5-14.0) with SOC (n = 107); the median OS with cilta-cel was NR (95% CI, NE-NE) vs 38.0 months (95% CI, 34.0-NE) with SOC. Lastly, in those with at least 2 cytogenetic abnormalities who received cilta-cel (n = 43), the median PFS was 29.8 months (95% CI, 10.8-NE) and the median OS was NR (95% CI, 29.8-NE); with SOC (n = 49), the median PFS was 6.7 months (95% CI, 4.7-10.3) and the median OS was 23.0 months (95% CI, 17.3-NE).
“Compared with SOC, cilta-cel improved PFS and OS in patients with high-risk cytogenetics, suggesting it may overcome the poor prognosis associated with these high-risk features,” Sidana said.
Disclosures: Sidana disclosed serving in a consultant or advisory role for AbbVie, BiolineRx, BMS/Celgene, Genentech/Roche, Johnson & Johnson, Kite, Legened Biotech, Pfizer, Regeneron, and Sanofi. Institutional research funding has been received by AbbVie, Allogene Therapeutics, BMS/Celgene, Johnson & Johnson, Magenta Therapeutics, and Novartis.
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