Atezolizumab Elicits Durable Responses in R/R Extranodal NK/T-Cell Lymphoma

Atezolizumab (Tecentriq) monotherapy demonstrated durable efficacy in patients with relapsed/refractory extranodal natural killer/T-cell lymphoma (ENKTL), according to results from the phase 2 NCCH1903/ATTACK trial (jRCT2031190177).¹

Of 13 evaluable patients, the independent review committee (IRC)-assessed objective response rate (ORR) was 54%, including 4 complete responses (31%), meeting the trial’s primary end point. Responses proved durable over extended follow-up; over a median follow-up period of 24.9 months, the median duration of response was not reached. Regarding survival outcomes, the median progression-free survival was 2.4 months, and the median overall survival was 10.3 months.

The safety profile was consistent with the known safety profile of immune checkpoint inhibitors and was considered manageable. Among the adverse events reported in the study, fever, neutropenia, anemia, leukopenia, and hypoalbuminemia were observed most frequently (≥30%).

ATTACK Trial Design and Patient Characteristics

The multicenter, single-arm phase 2 study aimed to evaluate the efficacy and safety of atezolizumab monotherapy in patients with R/R ENKTL, with the primary end point of objective response rate as assessed by IRC. The trial was conducted across 4 institutions in Japan and enrolled patients with R/R ENKTL who had received at least 1 prior line of therapy.

Fourteen patients were ultimately enrolled, with 13 evaluable for response. The median patient age was 72 years (range, 27-80), 46% were female, and 77% had an ECOG performance status of 1. Atezolizumab was administered as monotherapy at 1200 mg intravenously every 3 weeks for up to 2 years or until disease progression or unacceptable toxicity.

Biomarker Analyses

Investigators also explored whether PD-L1 genomic and protein-expression status could predict response to atezolizumab. Structural variations involving the PD-L1 locus were assessed using targeted-capture sequencing; structural variations in PD-L1 were detected in 4 of 11 evaluable patients (36%), and patients harboring these alterations appeared more likely to respond to treatment. The ORR in patients with PD-L1 structural variations was 75% (n = 3/4), while 3 of 7 patients without these variations achieved responses, amounting to an ORR of 43%.

A similar pattern emerged with PD-L1 protein expression assessed by immunohistochemistry (IHC). PD-L1 expression was positive in 5 of 11 evaluable patients (45%) by IHC. Response rates diverged notably by expression status. The ORR in the PD-L1–positive group was 80% (n = 4/5) vs 33% (n = 2/6) in patients without PD-L1 expression.

Limitations and Clinical Implications

ENKTL is a rare and aggressive type of non-Hodgkin lymphoma associated with Epstein-Barr virus that occurs more frequently in East Asia relative to Western countries.² Although advances in treatment have improved outcomes, treatment options remain limited in the relapsed/refractory setting, particularly after failure of asparaginase-containing regimens. Outcomes following relapsed/refractory disease remain poor, underscoring the need for effective and tolerable salvage approaches.

Taken together, the data support a potential role for atezolizumab in patients with R/R ENKTL, particularly given the durability of responses observed in a population with historically poor outcomes after failure of asparaginase-containing regimens. PD-L1 genetic alterations and expression levels may additionally serve as predictive biomarkers to help identify patients most likely to benefit from anti–PD-L1 therapy in this setting.

The authors noted several limitations that should be considered when interpreting the findings, such as the small sample size lack of a comparator arm, limitations inherent to its single-arm design. The rarity of ENKTL relative to B-cell lymphomas also presents challenges for conducting large, randomized clinical trials in this population.

“To our knowledge, this is the first report to evaluate the efficacy and safety of atezolizumab in patients with R/R ENKTL,” study authors Makita et al wrote in the publication. “Atezolizumab demonstrated clinically meaningful efficacy in patients with R/R ENKTL.”

REFERENCES

1. Makita S, Koya J, Suzuki Y, et al. Atezolizumab for relapsed/refractory extranodal NK/T-cell lymphoma: phase 2 of NCCH1903/ATTACK trial. Blood Adv. 2026;10(15):5276-5284. doi:10.1182/bloodadvances.2026019929

2. Makita S, Tobinai K. Clinical Features and Current Optimal Management of Natural Killer/T-Cell Lymphoma. Hematol Oncol Clin North Am. 2017;31(2):239-253. doi:10.1016/j.hoc.2016.11.007