Atezolizumab for relapsed/refractory extranodal NK/T-cell lymphoma: phase 2 of NCCH1903/ATTACK trial

ABSTRACT: Extranodal natural killer/T-cell lymphoma (ENKTL) is rare, and treatment options for relapsed/refractory (R/R) disease are limited. This multicenter, single-arm phase 2 study evaluated the efficacy and safety of atezolizumab monotherapy in patients with R/R ENKTL. The primary end point was 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 years (range, 27-80), 46% were female, and 77% had an Eastern Cooperative Oncology Group performance status of 1. The IRC-assessed ORR was 54% (7/13), including 4 complete responses (31%). Over a median follow-up period of 24.9 months, the median duration of response was not reached. Median progression-free survival and overall survival were 2.4 and 10.3 months, respectively. Structural variations (SVs) in programmed cell death ligand 1 (PD-L1) were detected in 4 of 11 evaluable patients (36%) by targeted-capture sequencing and/or fluorescence in situ hybridization. The ORR in those patients was 75% (3/4), whereas 3 of 7 patients without PD-L1 SVs responded (ORR, 43%). PD-L1 expression was positive in 5 of 11 evaluable patients (45%) by 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 response to this approach. This trial was registered at the Japan Registry of Clinical Trials (jRCT2031190177).