侵袭性 B 细胞淋巴瘤 CAR-T 细胞治疗后的迟发失败：来自 DESCAR-T 注册登记的一项 LYSA 研究

Large B-cell lymphoma (LBCL) patients failing anti-CD19 chimeric antigen receptor (CAR) T-cell therapy exhibit poor prognosis. Most progressions/relapses occur within 3 months from infusion whereas only a few events occur thereafter (late failure, [LF]).

We analyze features, treatments, and outcomes of patients with LF from DESCAR-T, a nationwide registry collecting real-life data for patients treated with approved CAR T-cell therapy in France. Between July 2018 and March 2024, 298 (39. 9%) LBCL LF patients (median age, 62 years [range, 18-79]; male, 61. 7%) were collected from DESCAR-T. Most patients had diffuse LBCL (n = 205 [68. 8%]), advanced stage disease (84. 6%), and age-adjusted International Prognostic Index of 2 to 3 (59. 3%) at CAR T-cell eligibility. After failure, 76. 5% of patients received a systemic therapy and overall response rate was 22. 6% (complete response, 18%). At a median follow-up since first LF event of 13. 8 months (95% confidence interval [CI], 12. 1-15.

4), the median overall survival and progression-free survival 2 (PFS-2) were 4. 4 (95% CI, 3. 8-5. 8) and 13. 2 (95% CI, 9. 6-18) months, respectively. Compared with chemotherapy (hazard ratio [HR], 0. 350; 95% CI, 0. 193-0. 633) and with pooled other treatment groups (HR, 0. 483; 95% CI, 0. 290-0. 805), salvage treatment with bispecific antibodies (bsAb) after CAR T-cell failure showed better PFS-2.

Radiotherapy obtained prolonged responses in some patients with 12-month PFS-2 of 41. 5% (95% CI, 22. 5-59. 5). This work is, to our knowledge, the first study describing LBCL patients with LF after CAR T-cells. bsAb seem to be more effective compared with other strategies in the LF setting and this should be considered in the design of new clinical trials.