P-020: Treatment Positioning Model to Evaluate the Survival Benefit of Ciltacabtagene Autoleucel in Second-Line Compared With Later-Line Treatment of Lenalidomide-Refractory Multiple Myeloma

Introduction: There are numerous potential benefits to early use of chimeric antigen receptor (CAR)-T cell therapies in patients (pts) with lenalidomide (len)-refractory multiple myeloma (MM). These include improved treatment responses, fewer pts lost to attrition/rapid progression, and potentially improved long-term outcomes. Ciltacabtagene autoleucel (cilta-cel) was recently approved based on the CARTITUDE-4 trial (NCT04181827), which demonstrated superior efficacy of cilta-cel vs physician’s choice of pomalidomide, bortezomib, and dexamethasone, or daratumumab, pomalidomide, and dexamethasone in pts with relapsed/refractory MM (RRMM) who received 1–3 prior lines of therapy (LOT) and were len refractory. We adapted a modeling approach to evaluate the survival benefit of using cilta-cel earlier in the treatment pathway in relapsed, len-refractory MM pts.

Methods: A Markov model was used to compare the survival benefit of using cilta-cel in second line (2L) followed by standard of care (SOC) in third line or greater (3L+) vs using SOC in 2L followed by cilta-cel in 3L+. SOC was defined based on the treatment regimens received by pts with len-refractory MM previously treated with 2L and 3L+, respectively, in the Flatiron Health database, with different distributions of treatments between 2L and 3L+. Inclusion/exclusion criteria of the CARTITUDE-4 population were applied to the SOC population from the Flatiron cohort and weighted on key prognostic factors and treatment effect modifiers. Time spent in 2L and 3L+ was defined by time to next treatment and overall survival (OS) derived from CARTITUDE-4 and Flatiron 2L and 3L+ subgroup datasets, respectively. Standard parametric survival models were used to estimate the transition probabilities over time. Attrition rates were defined by the number of deaths divided by deaths plus the number of those who progressed from the Flatiron dataset and were assumed to be the same in both arms.

Results: The cilta-cel arm of the CARTITUDE-4 intent-to-treat cohort consisted of 208 pts (data cut-off, November 2022; median follow-up, 16 months) and the adjusted Flatiron cohort consisted of 1977 observations (data from February 2016–December 2022; median follow-up, 34 months). According to this simulation model, using cilta-cel in 2L resulted in longer OS benefit compared with using cilta-cel in 3L+ after SOC (8.8 vs 5.5 years, respectively). When cilta-cel was used in 2L, predicted OS rates at 5, 10, and 15 years were 69.6%, 45.6%, and 31.9%, respectively, compared with 53.0%, 33.6%, and 24.0% when cilta-cel was used in 3L+. Results of scenario analyses consistently demonstrated the survival benefit of using cilta-cel in 2L vs 3L+.

Conclusions: Our simulated model suggests that using a single infusion with cilta-cel earlier might result in better survival outcomes for len-refractory pts with RRMM. However, more investigation, including comparison of real-world data is needed to test the results seen with this model.