TOPLINE:

In patients with newly diagnosed extranodal natural killer/T-cell (NK/T) lymphoma, first-line programmed death-1 (PD-1) inhibitors combined with asparaginase-based chemotherapy were associated with significant improvements in progression‑free survival (PFS) and overall survival in a large-scale study. The association was particularly pronounced among those with advanced-stage or intermediate-/high-risk disease. The PD-1 regimen was also associated with higher rates of hematologic toxicity and rare severe immune‑related adverse events but fewer fatal infections. 

METHODOLOGY:

• Extranodal NK/T lymphoma is an aggressive lymphoma with poor outcomes in advanced disease despite radiotherapy and asparaginase‑based regimens. Although PD‑1 inhibitors are effective in relapsed/refractory cases, their role as frontline therapy in treatment-naive patients with the disease remains unclear.
• To evaluate whether adding PD-1 blockade to asparaginase‑based regimens improves survival, researchers conducted a large-scale retrospective study of 755 patients with newly diagnosed extranodal NK/T lymphoma (median age, 52 years); those who received at least one dose of a PD‑1 inhibitor as first-line therapy were classified as the PD-1 inhibitor cohort, and the remaining were classified as the non‑PD-1 inhibitor cohort.
• Patients in the PD-1 inhibitor cohort vs non‑PD-1 cohort were older at diagnosis (median, 56 vs 51 years) had a higher prevalence of non-upper aerodigestive tract primary sites (18.5% vs 11.9%) and advanced-stage disease (53.3% vs 42.1%), and were more likely to be classified intermediate-/high-risk by prognostic indices.
• Study outcomes were PFS and overall survival. The median follow-up duration was 32.9 months.
• Overall, 17.9% of patients received at least one dose of first-line PD-1 inhibitors, with tislelizumab (42.3%) and sintilimab (36.2%) being the most commonly used agents, and 88.9% received asparaginase-based regimens. Among PD-1 inhibitor recipients, 78.5% received concurrent induction chemotherapy (60.0% received concurrent induction only, and 18.5% received concurrent induction followed by maintenance), and 21.5% received PD-1 inhibitors as the maintenance strategy.

TAKEAWAY:

• In the entire cohort, first-line PD-1 inhibitor treatment was associated with improved PFS (hazard ratio [HR], 0.62; P = .007) and overall survival (HR, 0.55; P = .027). The 5-year PFS rates were 62.6% in the PD-1 inhibitor group compared to 49.8% in the non-PD-1 inhibitor group; 5-year overall survival rates were 83.9% in the PD-1 inhibitor group compared to 70.8% in the non-PD-1 inhibitor group.
• In advanced-stage disease, the 5-year PFS rates were 63.2% vs 24.0%, in favor of the PD-1 group, and overall survival was 77.7% in the PD-1 inhibitor vs 47.7% in the non-PD-1 inhibitor group. PFS also improved significantly for patients classified as intermediate‑risk and high‑risk.
• PD-1 inhibitors remained independently associated with improved outcomes (HR range, 0.40-0.50; P ≤ .004 for all), a finding that persisted in propensity score-matched analysis (PFS: HR, 0.57; overall survival: HR, 0.45).
• The addition of PD-1 inhibitors increased hematologic toxicities of grade 3 or higher — lymphopenia (62.5% vs 55.6%), neutropenia (45.2% vs 31.6%), leukopenia (43.3% vs 28.9%), and thrombocytopenia (31.7% vs 19.2%) — but with fewer fatal infections observed (0 vs 3) and rare severe immune‑related adverse events (1%).

IN PRACTICE:

Findings from this study suggested that “frontline [PD-1 inhibitors], particularly in combination with [asparaginase]‑based therapy, may represent a promising strategy that is associated with improved survival and could help address traditional prognostic barriers in advanced and intermediate/high‑risk [extranodal NK/T lymphoma],” the authors wrote, adding that prospective randomized trials are warranted to define the optimal regimens, minimize toxicity, and develop strategies to overcome resistance.

SOURCE:

The study, led by Hailing Liu, Jiangsu Province Hospital, the First Affiliated Hospital with Nanjing Medical University in Nanjing, China, was published online in the American Journal of Hematology.

LIMITATIONS:

The study was retrospective and nonrandomized, so unmeasured confounding and indication bias could not be fully excluded. Variable timing of PD‑1 initiation required time‑varying adjustment but could still bias results. Additionally, treatment heterogeneity and pooling of different PD‑1 agents limited assessment of agent‑specific effects.

DISCLOSURES:

This study received support through grants provided by the National Natural Science Foundation of China, the Natural Science Foundation of Jiangsu Province, the Jiangsu Province Hospital High-Level Hospital Construction Project, the Specialized Diseases Clinical Research Fund of Jiangsu Province Hospital, and the Baiqiuen Medical Science Research Foundation. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.