Transfusion needs after CAR T-cell therapy for large B-cell lymphoma: predictive factors and outcome. A DESCAR-T study.

Chimeric antigen receptor (CAR) T-cells targeting CD19 have been approved for the treatment of relapse/refractory large B-cell lymphoma. Hematotoxicity is the most frequent CAR T-cell-related adverse event. Transfusion support is a surrogate marker of severe cytopenias. Transfusion impacts patients' quality of life, presents specific toxicities and is known to affect immunity through the so-called transfusion-related immunomodulation, that may impact CAR T-cell efficacy. We analyzed data from 671 patients from the French DESCAR-T registry for whom exhaustive transfusion data were available. Overall, 401 (59.8%) and 378 (56.3%) patients were transfused in the 6-month period before and after CAR T-cell, respectively. The number of transfused patients and the mean number of transfused products increased during the 6-month period before CAR-T, peaked during the first month after infusion (early phase) and decreased over time. Predictive factors for transfusion at the early phase were age > 60 years, ECOG PS ≥2, treatment with axi-cel, pre-CAR T-cell transfusions and CAR-HEMATOTOX score ≥ 2. Predictive factors for late transfusion (between 1 and 6 months after infusion) were pre-CAR T-cell transfusions, CAR-HEMATOTOX score ≥ 2, ICANS ≥ 3 (for red blood cells [RBC] transfusion) and tocilizumab use (for platelets transfusion). Early transfusions and late platelets (but not RBC) transfusions were associated with a shorter progression-free survival and overall survival. Lymphoma-related mortality and non-relapse mortality were both increased in the transfused population. Our data shed light on the mechanisms of early and late cytopenia, and on the potential impact of transfusions on CAR T-cell efficacy and toxicity.