CAR-T Therapy in Patients 75+ with Relapsed/Refractory DLBCL | Pierre Bories, MD, PhD | EHA 2024

Hello, my name is Pierre Boré. I'm a nematologist in Toulouse University Hospital, south of France. I represent you the results of our real life assessment of CD19 CAR-T for large B-cell lymphoma patients treated above the age of 75. It is obvious that CD19 CAR-T has transformed the therapeutic landscape of large B-cell lymphoma patients. However, elderly patients might pose different challenges, with immunosensance being a potential limit for efficacy and higher comorbidity burden associated with higher toxicity. Patient selection above the age of 75 might be a critical issue. Also, those patients were underrepresented in clinical trials. We aim with the Descartes Registry study to evaluate the outcome of large B-cell lymphoma patients treated with CD19 CAR-T above the age of 75 and to compare with those of younger patients. We leveraged the Descartes Registry between September 2018 and December 2023 among the 31 French centers qualified for CAR-T during this period of time. We identified 1,524 patients infused with CD19 CAR-T in the third line setting and among them 1,399 patients below 75 and 125 patients above 75. Regarding patient characteristics, we observed in the older group a higher proportion of patients with high comorbidity score and a lower proportion of patients treated with previous autologous transplantation. There were no differences in terms of gender, eco-performance status, age-adjusted IPI score and number of previous lines. At the time of infusion, we observed no difference in terms of bridging therapy and response to the bridging therapy. Around 80% of patients received the bridging therapy and 30% of patients were infused either in PR or CR. No difference in terms of LDH level, CAR-ematotox score. And finally, we observed a difference in the CAR-T infused with, as anticipated, more patients infused with TISA cell above 75 and less patients with TISA cell below 75. There was no differences in terms of response rate. The overall response rate was 75% in both groups and the complete response rate was 60%. No difference in terms of duration of response with a median follow-up of 12.7 months. The median DOR was 15 months below 75 compared to 11 months above 75. Accordingly, the progression free survival was not different between the two groups and the overall survival was not statistically different, quantified as 24 months below 75 and 18 months above 75. The safety was not different between the two groups. Grade III or higher CRS occurred in about 7% of the entire cohort and grade III or higher neurotoxicity was observed in 12% of patients below 75 compared to 10% above 75. There was no difference in terms of ICU admission and mechanical ventilation. Finally, we observed a difference in terms of non-relapse mortality, which was quantified at 19.5% above 75 compared to 8.1% below 75. This difference in non-relapse mortality mainly relies on infectious events that were late events and the early non-relapse mortality was not different between the two groups quantified at 1.2% below 75 and 2.4% above 75. With our findings as a conclusion, we think our findings support the feasibility of CD19 in CAR-T above the age of 75 with similar efficacy and survival compared to younger population. Immunosensors do not seem to compromise CAR-T efficacy. However, we show a higher non-relapse mortality in elderly patients that mainly relies on late infectious events and did not translate into overall survival disadvantage. As a perspective, we are currently producing a propensity match comparison between AxiCell and TISA cell in this elderly population. Thank you for your attention.