大 B 细胞淋巴瘤患者进展至 CAR-T 细胞治疗后的治疗结局

Over 60% of relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients who receive chimeric antigen receptor (CAR) T cells will experience disease progression. There is no standard next line of therapy and information in this setting is scarce and heterogeneous.

We analyzed 387 R/R LBCL patients who progressed after CAR T cells from July 2018 until March 2022 in Spain and the United Kingdom. Median overall survival (OS) was 5. 3 months, with significant differences according to the interval between infusion and progression (<2 months [1. 9 months], 2-6 months [5. 2 months], and >6 months [not reached]). After progression, 237 (61%) patients received treatment.

Focusing on the first subsequent therapy, overall (complete) response rates were 67% (38%) for polatuzumab-bendamustine-rituximab (POLA), 51% (36%) for bispecific antibodies (BsAb), 45% (35%) for radiotherapy (RT), 33% (26%) for immune checkpoint inhibitors (ICIs), 25% (0%) for lenalidomide (LENA), and 25% (14%) for chemotherapy (CT).

In terms of survival, 12-month progression-free survival and OS was 36. 2% and 51. 0% for POLA, 32. 0% and 50. 1% for BsAb, 30. 8% and 37. 5% for RT, 29. 9% and 27. 8% for ICI, 7. 3% and 20. 8% for LENA, and 6. 1% and 18. 3% for CT. Thirty-two (14%) patients received an allogeneic hematopoietic cell transplant with median OS not reached after a median follow-up of 15. 1 months.

In conclusion, patients with R/R LBCL who progress within the first 2 months after CAR T-cell therapy have dismal outcomes. Novel targeted agents, such as polatuzumab and BsAbs, can achieve prolonged survival after CAR T-cell therapy failure.