CAR-T in the older adults: Real-world survival and toxicity in patients ≥ 75 years with relapsed/refractory multiple myeloma.

Abstract

7541 Background: CAR-T cell therapy targeting BCMA has transformed the treatment landscape for relapsed/refractory multiple myeloma (RRMM). However, pivotal clinical trials have limited representation of patients aged ≥75 years, leaving the safety and effectiveness of CAR-T therapy in this older population undercharacterized. In this study, we sought to evaluate the real-world outcomes of CAR-T therapy in patients aged ≥75 years with RRMM. Methods: A retrospective cohort study was conducted using the TriNetX database, which includes data from a large network of healthcare institutions in the US. Adult patients with RRMM who received CAR-T therapy were identified and stratified into two age based cohorts: ≥75 years and <75 years. Propensity score matching (1:1) was performed based on race, gender, comorbidities, and high risk cytogenetics if available. Outcomes included incidence of immune effector cell-associated neurotoxicity syndrome (ICANS), cytokine release syndrome (CRS), tocilizumab (Toci) use, sepsis, 30-day intensive care unit (ICU) admission rates, 90-day mortality rate, and 1 and 3-year overall survival (OS). Cox proportional hazards multivariate analysis was used to assess the impact of age on OS, controlling for confounders. Results: A total of 1,392 patients met study criteria, of which 198 patients were aged ≥75 yrs at the time of infusion. The mean age was 62.6 vs. 77.5 yrs in the younger and older cohort, respectively. Prior to propensity score matching (PSM), there were no significant differences in the rates of CRS, ICANS, Toci, sepsis, or 30-day ICU admissions rate post-infusion. Grade 3 or higher CRS/ICANS were infrequent in both cohorts. Additionally, the 90-day mortality rate did not differ significantly between the older and younger cohorts. Following PSM, these findings remained consistent (Table 1). While there was no significant difference in 1-year OS, the 3-year OS was lower in the ≥75 cohort (69% vs. 55.4%, log rank p=0.51), although the difference was not statistically significant. Cox proportional hazards multivariate analysis, controlling for race, gender, and comorbidities, revealed that age ≥75 was not independently associated with OS (hazard ratio [HR] = 1.04, 95%CI 0.65-1.65, p = 0.87). Conclusions: In this real-world cohort of RRMM patients receiving CAR-T therapy, age ≥75 years was not associated with differences in risks of CRS, ICANS, sepsis, 90-day mortality, or 1-year overall survival. While 3-year overall survival was lower in patients ≥75 years, possibly due to competing mortality risks, these findings overall suggest that age alone should not preclude BCMA-directed CAR T-cell therapy in select older patients. Outcome <75 years(n=197) ≥75 yrs (n=197) p-value CRS 53% 46% 0.27 ICANS 12% 8% 0.22 TOCI use 53% 51% 0.82 ICU admission 3.8% 5.1% 0.39 Sepsis 6% 7.9% 0.36 90 day mortality 3.9% 5% 0.28 1-yr OS 86.2% 86.6% 0.86 3-yr OS 69% 55.4% 0.51