Identifying Key Predictors of Early Relapse After Treatment With Ciltacabtagene Autoleucel to Inform Risk-Adapted Strategies for Patients With R/R MM
Key Clinical Summary
- Population and Design: Multi-center retrospective analysis of 598 R/R MM patients (median age 65 y; median 5 prior lines) who received ciltacabtagene autoleucel (cilta-cel) between May 2022 to December 2024; 33% functional high-risk (FHR), 43% cytogenetically high-risk, 42% IMS-IMWG high-risk, and 11% with EMD.
- Efficacy: ORR 89% vs 94% and CR 61% vs 75% in FHR vs non–high-risk patients; similar CR reductions observed in cytogenetic (65% vs 74%), IMS-IMWG (64% vs 75%), and EMD (61% vs 71%) subgroups. 12-month PFS markedly lower for FHR (55% vs 79%) and other high-risk categories.
- Clinical Relevance: Functional and adapted high-risk features independently predicted early relapse (≤ 18 mo) after cilta-cel (FHR OR 3.04; IMS-IMWG OR 2.07), supporting risk-adapted approaches—including bridging, consolidation, or maintenance strategies—to optimize outcomes in high-risk R/R MM.
According to research presented by Doris Hansen, MD, H. Lee Moffitt Cancer Center and Research Institute, Tampa, Florida, at the 2025 American Society of Hematology (ASH) Annual Meeting & Exposition in Orlando, Florida, identifying functional high-risk (FHR) disease and adapted high-risk cytogenetic features as possible predictors of early relapse following treatment with ciltacabtagene autoleucel (cilta-cel) among patients with relapsed/refractory (R/R) multiple myeloma (MM) can inform risk-adapted strategies and interventional trials with the aim to create superior outcomes for these patients.
Researchers conducted a multi-center retrospective analysis to determine the efficacy of ciltacabtagene autoleucel among patients with R/R MM who received ciltacabtagene autoleucel between May 2022 and December 2024.
Overall, 598 patients were included, and the median age was 65 years (range, 33 to 83). The median prior lines of therapy were 5 (range, 1 to 18), with 84% of patients received >3 prior lines. At baseline, 33% had functional high-risk disease, which was defined as relapse within 18 months of first-line therapy, 43% of patients had traditional high-risk cytogenetics, 42% of patients met adapted IMS-IMWG high-risk criteria, and 11% of patients had extramedullary disease (EMD). Most patients (88%) received bridging therapy prior to infusion.
At a median follow-up of 10.6 months, the overall response rate (ORR) was lower among patients with functional high-risk disease (89%) than patients without any high-risk feature (94%). The complete response (CR) rates were also lower among patients with functional high-risk disease (61%) than patients without any high-risk feature (75%).
Similar trends were seen in patients with high-risk cytogenetics compared with patients without high-risk features including a CR rate of 65% vs. 74%. Patients with IMS-IMWG high-risk had a CR rate of 64% vs. 75% among patients without high-risk features. Patients with extramedullary disease also had a lower CR rate of 61% vs. 71%.
The 12-month progression-free survival (PFS) was also reduced in these groups compared to patients without any high-risk features:
- functional high-risk (55% vs. 79%),
- traditional high-risk (63% vs. 78%),
- IMS-IMWG high-risk (61% vs. 80%), and
- extramedullary disease (59% vs. 73%).
Among 247 patients with ≥18 months of follow-up, early relapse (≤18 months post-infusion) was significantly associated with functional high-risk disease (odds ratio [OR] = 3.04) and adapted IMS-IMWG high-risk status (OR = 2.07), but not extramedullary disease.
The researchers concluded, “While cilta-cel leads to high response rates and durable PFS in RRMM, a subset of patients with FHR and adapted IMS-IMWG HR remains at increased risk for early relapse.”
They added, “These findings inform risk-adapted therapeutic strategies and interventional trials, including bridging, consolidation, or maintenance approaches, to improve outcomes in the highest-risk RRMM patients.”
Source:
Hansen D, Peres L, Dima D, et al. Predictors of early relapse following ciltacabtagene autoleucel: Informing risk-adapted therapy in relapsed/refractory multiple myeloma. Dec 6-9, 2025; Orlando, FL. Abstract: 93
