Atezolizumab for relapsed/refractory extranodal NK/T-cell lymphoma: the phase II NCCH1903/ATTACK trial

Extranodal NK/T-cell lymphoma (ENKTL) is rare and has limited treatment options available for relapsed/refractory (R/R) disease. This multicenter single-arm phase II study evaluated the efficacy and safety of atezolizumab monotherapy in patients with R/R ENKTL. The primary endpoint was the objective response rate (ORR), as assessed by an independent review committee (IRC). Fourteen patients were ultimately enrolled. Among the 13 with evaluable responses, the median age was 72 (range, 27-80) years, 46% were female, and 77% had Eastern Cooperative Oncology Group Performance Status of 1. The IRC-assessed ORR was 54% (7/13), which included four complete responses (31%). Over a median follow-up period of 24.9 months, the median response duration was not reached. The median progression-free and overall survival were 2.4 and 10.3 months, respectively. Structural variations (SVs) in the programmed cell death-ligand 1 (PD-L1) were detected in 4/11 evaluable patients (36%) via targeted-capture sequencing and/or fluorescence in situ hybridization. The ORR in those patients was 75% (3/4), while 3/7 patients without PD-L1 SVs achieved responses (ORR, 43%). PD-L1 expression was positive in 5/11 evaluable patients (45%) via immunohistochemistry. The ORR in that group was 80% (4/5), vs 33% (2/6) in those without PD-L1 expression. Atezolizumab demonstrated clinically meaningful efficacy with durable responses in patients with R/R ENKTL. PD-L1 genetic alterations and/or PD-L1 expression levels may represent predictive biomarkers of patient responses to this approach. This trial was registered in the Japan Registry for Clinical Trials (jRCT2031190177).