Outcomes of patients with aggressive B-Cell lymphoma after failure of anti-CD19 CAR T-Cell Therapy: A DESCAR-T analysis.

Anti-CD19 CAR T-cells represent a major advance in the treatment of relapsed/refractory aggressive B-cell lymphomas. However, a significant number of patients experiences failure. Among 550 patients registered in the French registry DESCAR-T, 238 (43.3%) experienced progression/relapse, with a median follow-up of 7.9 months. At registration, 57.0% of patients presented an age adjusted International Prognostic Index of 2-3, 18.9% had ECOG performance status ≥2, 57.1% received >3 lines of treatment prior to receiving CAR T-cells, and 87.8% received bridging therapy. At infusion, 66% of patients presented progressive disease and 38.9% high lactate dehydrogenase (LDH). Failure after CAR T-cells occurred after a median of 2.7 months (range, 0.2-21.5). Fifty-four (22.7%) patients presented very early failure (day [D] 0-D30); 102 (42.9%) had early failure (D31-D90), and 82 (34.5%) had late (>D90) failure. After failure, 154 (64%) patients received salvage treatment: 38.3% had lenalidomide, 7.1% bispecific antibodies, 21.4% targeted treatment, 11% radiotherapy, and 20% immuno-chemotherapy with various regimens. Median progression-free survival was 2.8 months, and median overall survival (OS) was 5.2 months. Median OS for patients failing during D0-D30 versus after D30 was 1.7 vs 3.0 months respectively (p=0.0001). Overall, 47.9% of patients were alive at 6 months, but only 18.9% were alive after very early failure. In multivariate analysis, predictors of OS were high LDH at infusion, time to CAR-T failure <D30, and high C-reactive protein at infusion. This multicentric analysis confirms the poor outcome of patients relapsing after CAR T-cells, highlighting the need for further strategies dedicated to this population.