既往 CAR-T 细胞治疗对复发/难治性 B 细胞淋巴瘤患者 mosunetuzumab 疗效的影响

Mosunetuzumab and other CD20/CD3 bispecific antibodies (BsAbs) have efficacy in B-cell lymphomas relapsing after or refractory to CD19-directed chimeric antigen receptor (CAR)-modified T cells (CAR-T). The optimal timing of BsAbs and biomarkers of BsAb response after CAR-T are unknown.

We addressed these questions using clinical data and blood samples from patients previously treated with CAR-T and subsequently treated on a phase 1/2 study of mosunetuzumab. Thirty patients had paired samples at baseline and after 1 cycle of mosunetuzumab. The median time from CAR-T to mosunetuzumab was significantly longer for responding than for nonresponding patients (P = . 006, unadjusted for multiple comparisons).

Most patients (20/30) did not receive intervening therapy between CAR-T administration and mosunetuzumab. The remainder of patients received 1 intervening therapy after a protocol-mandated drug washout. After mosunetuzumab, responding patients had higher lymphocytes (995 vs 400 cells per L; P = . 02) and greater increases in CD4 and CD8 cells (median change, 73 vs -90 cells per L [P = . 005] and 243 vs -103 cells per L [P = . 004], respectively).

Additionally, responding patients had an increase in activated CD8 cells (median fold change, 1. 7; P = . 02). Nonresponders had a relative decrease in CAR transgene levels (n = 16; P = . 04). This is, to our knowledge, the first study to assess changes in lymphocytes, T cells, and CAR transgene levels in patients treated with BsAbs after CAR-T.

These findings suggest an interaction between prior CAR-T and BsAb outcomes and have implications for optimal timing of BsAb after CAR-T. The trial was registered at www. ClinicalTrials. gov as #NCT02500407.