Non-Relapse Mortality after CAR T-Cell therapy for Large B-Cell Lymphoma: A LYSA Study from the DESCAR-T Registry.

CD19 chimeric antigen receptor (CAR) T-cells can induce prolonged remissions and potentially cure a significant proportion of patients with relapsed/refractory (r/r) large B-cell lymphomas (LBCL). However, some patients may die of causes unrelated to lymphoma after CAR T-cell therapy. To date, little is known about the non-relapse mortality (NRM) following CAR T-cells. Using the French DESCAR-T registry, we analyzed the incidence and causes of NRM, and identified risk factors of NRM. We report 957 patients who received standard-of-care (SOC) axicabtagene ciloleucel (axi-cel; n=598) or tisagenlecleucel (tisacel; n=359) between July 2018 and April 2022, in 27 French centers. With a median follow-up of 12.4 months, overall NRM occurred in 48 patients (5.0% of all patients): early (<day 28 pos-infusion) in 9 patients (0.9% of all patients and 19% of overall NRM), and late (≥day 28 pos-infusion) in 39 patients (4.1% of all patients and 81% of overall NRM). Causes of overall NRM were distributed as follows: 56% of infections (29% non-COVID infection, 27% COVID infection), 10% of cytokine release syndromes (CRS), 6% of strokes, 6% of cerebral hemorrhages, 6% of second malignancies, 4% of immune effector cell associated neurotoxicities (ICANS), and 10% of deaths from other causes. We report risk factors for early NRM and overall NRM. In multivariate analysis, both diabetes and elevated ferritin at lymphodepletion were associated with an increased risk of overall NRM. Our results may help physicians in patient's selection and management in order to reduce the NRM after CAR T-cell therapy.