Non-relapse mortality in patients who received CAR T-cell therapy at an urban hospital

Abstract Introduction: Chimeric antigen receptor (CAR) T-cell therapy is an effective therapy for patients (pts) who suffer from relapsed / refractory multiple myeloma (MM) and diffuse large B-cell lymphoma (DLBCL) {Goyco Vera, D., 2024; Locke, F. L., 2022; Mikkilineni, L., 2017; Svoboda, J., 2025}. Few studies have evaluated non-relapse mortality (NRM) in these pts from infectious complications, cytopenia, ICANS/CRS, secondary malignancies {Cordas dos Santos, David M., 2024}. As we expand treatment to earlier lines in DLBCL and MM, there is a need to better understand the causes of NRM which impacts the overall survival (OS). We performed a retrospective analysis of pts with DLBCL and MM who underwent CAR T-cell therapy at our institution. Methods: Patients who underwent CAR T-cell therapy for DLBCL and MM from May 2016 to September 2024 at Karmanos Cancer Institute in Detroit, Michigan were included in the retrospective data analysis. Causes of NRM were also collected NRM and defined as the time from CAR T-cell therapy administration to death without relapse as a competing risk, and OS was defined as the time from CAR T-cell administration to death from any cause. Age at CAR T-cell therapy, race, sex, and Karnofsky performance (KPS) status at the time of CAR T-cell therapy were included as covariates in the multivariable analyses. Results: Data was collected for a total of 173 pts who underwent CAR T-cell therapy, 102 who were diagnosed with DLBCL and 71 who were diagnosed with MM. The median age of our population was 64 years (median interquartile range 55-71). Racial distribution differed significantly between pts with DLBCL and MM (p<0.001), with black patients constituting a larger portion of the MM cohort (26.8%) compared to DLBCL (6.9%). There was no statistically significant gender difference amongst our patient population (68 females, 105 males). The median KPS status at the time of CAR T-cell therapy was 80% (range 60%-100%). With median follow up of 1.78 yrs (95% C1, 1.42-2.18) and 2.05 yrs (95% CI 1.5-2.83) for MM and DLBCL pts, the median survival was 3.12 yrs (95% CI 2.17-NR) and 2.59 (1.76-NR), respectively. 64 pts died. 40 of these pts had DLBCL and 24 pts had MM. 23 pts in our cohort experienced NRM, 16 of whom had DLBCL, and 7 of whom had MM. In addition, there were no statistically significant differences in the causes of NRM (infectious (12/23), ICANS/CRS (1/23), secondary malignancy (2/23), and other (8/23)). Among 16 pts in the DLBCL cohort who experienced NRM, 6 pts had infection related causes and 1 pt each due to secondary malignancy or CRS/ICANS, and 8 due to other causes. Among 7 pts in the MM cohort who experienced NRM, 6 pts had infection related causes and 1 developed secondary malignancy. There were no statistical differences in pts who experienced NRM within race, sex, age, or KPS status. In multivariable analysis, we observed that male pts had a high hazard death from any cause (HR = 2.47, 95% CI: 1.36–4.50, p = 0.003). We also found that this analysis remained significant in DLBCL pts (HR = 2.83, 95% CI: 1.26–6.33, p = 0.011) but not in MM pts when analyzed separately. KPS status at the time of CAR T-cell therapy was also associated with poor OS in the univariable model (HR = 0.97, 95% CI: 0.94–0.999, p = 0.040; range 60%-100%) but was not significant in the multivariable analysis. Conclusion: In our patient population, we did not find a significant association with age. sex, race, or KPS status and NRM in patients who underwent CAR T-cell therapy for DLBCL and MM. As more pts become eligible for CAR T cell therapy, detailed analysis for NRM will be important to understand the morbidity/ mortality associated with this modality of treatment.