Effects of an Initial Anti-CD19 CAR T-cell Therapy on Subsequent Anti-CD22 CAR T-cell Manufacturing and Clinical Outcomes in Patients with r/r LBCL
Menée sur 37 patients atteints d'un lymphome à grandes cellules B réfractaire aux lymphocytes CAR-T anti-CD19, cette étude évalue l'impact d'un traitement initial par lymphocytes CAR-T anti-CD19 sur l'efficacité et la toxicité d'un traitement par lymphocytes CAR-T anti-CD22
Patients with large B-cell lymphoma that progresses after anti–CD19 chimeric antigen receptor (CAR) T-cell (CAR19) therapy have poor outcomes. Subsequent CAR T-cell therapy shows promise, but the impact of residual CAR19 and early relapse remains unclear. We evaluated 37 patients with CAR19-refractory large B-cell lymphoma who received anti–CD22 CAR T-cell (CAR22) in a phase Ib trial (NCT04088890). Residual CAR19 was unquantifiable in 17 of 33 evaluable patients post-CAR22 infusion. Single-cell RNA sequencing revealed minimal CAR19/CAR22 co-transduction. Peak CAR19 transgene levels did not affect CAR22 efficacy or toxicities. CAR22 products from patients undergoing leukapheresis ≥6 months after CAR19 had higher CD4+ naïve T and CD4+/CD8+ T central memory (TCM) cells, with lower CD4+ T effector memory (TEM) cells. High and low percentages of CAR22 TCM and TEM, respectively, were correlated with CAR22 transduction efficiency and complete response. Residual CAR19 and leukapheresis timing did not significantly affect outcomes, whereas CAR22 product composition was significantly correlated with treatment response.
Cancer Discovery 2024