Senl_B1922P

CD19 chimeric antigen receptor T-cell (CAR-T) therapy is efficacious for refractory/relapsed (R/R) B-cell hematological malignancies, yet relapse due to CD19 antigen escape remains a challenge. Our trial explored simultaneous targeting of multiple B-cell antigens as a therapeutic approach that may reduce the risk of relapse. We tested the safety and efficacy of CAR19/22 T-cell cocktail therapy including murinized and humanized products among patients with R/R aggressive B-cell lymphoma. In the group that received the humanized product, 11/12 (91.7%) patients achieved an objective response, including 9/12 (75%) complete responses (CRs) by day 28. The overall response rate and CR rate in the murinized group was 92.9% (13/14) and 42.9% (6/14), respectively. Nine of 12 (75%) patients in the humanized group maintained CR at month 3 following infusion, compared to 5/14 patients (35.7%) in the murinized group. Progression-free survival (PFS) was more favorable in the humanized compared to the murinized group. Most patients had mild cytokine release syndrome (CRS) (grade 1–2) in both groups. This study demonstrates that CAR19/22 T-cell cocktail therapy is safe and effective for R/R B-cell lymphoma and that patients treated with a humanized CAR-T exhibited better efficacy compared to patients treated with a murinized CAR-T therapy.

TP53gene alteration confers inferior prognosis in refractory/relapse aggressive B-cell non-Hodgkin lymphoma (r/r B-NHL). From September 2016 to September 2020, 257 r/r B-NHL patients were assessed for eligibility for two trials in our center, assessing anti-CD19 and anti-CD22 chimeric antigen receptor (CAR19/22) T-cell cocktail treatment alone or in combination with autologous stem cell transplantation (ASCT).TP53alterations were screened in 123 enrolled patients and confirmed in 60. CAR19/22 T-cell administration resulted in best objective (ORR) and complete (CRR) response rate of 87.1% and 45.2% in patients withTP53alterations, respectively. Following a median follow-up of 16.7 months, median progression-free survival (PFS) was 14.8 months, and 24-month overall survival (OS) was estimated at 56.3%. Comparable ORR, PFS, and OS were determined in individuals with or withoutTP53alterations, and in individuals at different risk levels based on functional stratification ofTP53alterations. CAR19/22 T-cell treatment in combination with ASCT resulted in higher ORR, CRR, PFS, and OS, but reduced occurrence of severe CRS in this patient population, even in individuals showing stable or progressive disease before transplantation. The best ORR and CRR in patients withTP53alterations were 92.9% and 82.1%, respectively. Following a median follow-up of 21.2 months, 24-month PFS and OS rates in patients withTP53alterations were estimated at 77.5% and 89.3%, respectively. In multivariable analysis, this combination strategy predicted improved OS. In conclusion, CAR19/22 T-cell therapy is efficacious in r/r aggressive B-NHL withTP53alterations. Combining CAR-T cell administration with ASCT further improves long-term outcome of these patients.