地西他滨预处理串联 CD19/CD22 CAR-T 治疗复发/难治性弥漫大 B 细胞淋巴瘤患者

Chimeric antigen receptor T cell (CAR-T) therapy has emerged as highly effective in relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL), but only about 40% patients have achieved sustained responses.

Here, we conducted a phase II clinical trial testing efficacy and toxicities of CAR-T therapy in R/R non-Hodgkin's lymphoma patients (NCT03196830). Among enrolled patients, 33 R/R DLBCL patients pretreated with DFC (decitabine, fludarabine plus cyclophosphamide) lymphodepletion chemotherapy and infused with tandem CD19-CD22 based CAR-T cells were drawn out for efficacy and toxicities of CAR-T therapy evaluation. With a median follow-up of 10. 9(0. 6-29. 0) months, the best overall response and complete remission (CR) rates were 90.

9% and 63. 6%, respectively. The median progression-free survival (PFS) was 10. 2 months and overall survival (OS) was undefined. The 2-year OS and PFS rates were 54. 3% and 47. 2%, respectively. No severe grade 4 cytokine release syndrome (CRS) was observed and grade 3 CRS was observed in only 7 patients; 3 patients developed mild immune effect or cell-associated neurotoxic syndrome. All toxicities were transient and reversible and no CAR-T-related mortality.

Further subgroup analysis showed that achieving CR was an independent prognostic factor associated with favorable PFS and OS. The 2-year OS and PFS for patients who achieved CR within 3 months (undefined versus undefined P =0. 021 and undefined versus undefined P =0. 036) or during the follow-up period were significantly longer than those who did not (undefined versus 4.

6 months P < 0. 0001 and undefined versus 2. 0months P <0. 001). While severe CRS was also an independent prognostic factor but associated with inferior PFS and OS. The 2-year OS and PFS for patients with grade 3 CRS were significantly shorter than those with grade 0-2 CRS (4. 1 months versus undefined P <0. 0001 and 1. 7 months versus undefined P =0. 0002).

This study indicated that CD19/CD22 dual-targeted CAR-T therapy under a decitabine-containing lymphodepletion regimen may be a safe, potent effective approach to R/R DLBCL patients.