Multicenter retrospective study of first-line PD1 inhibitors for extranodal NK/T-cell lymphoma

Programmed cell death 1 inhibitors (PD1i) are recommended in guidelines for relapsed/refractory extranodal NK/T-cell lymphoma (ENKTL). A multicenter retrospective study in China evaluated PD1i as first-line therapy for ENKTL. Among 755 newly diagnosed ENKTL patients, 17.9% received first-line PD1i. Despite harboring more adverse risk features, the PD1i group showed significantly improved progression-free survival (HR 0.62; p=0.007) and overall survival (HR 0.55; p=0.027) after a median follow-up of 32.9 months. The benefit was also observed in key subgroups (non-upper aerodigestive tract, advanced stage, intermediate- or high-risk). There was enhanced efficacy with PD1i-asparaginase combination therapy. Multi-state survival modeling indicated that PD1i primarily delays disease progression rather than post-progression mortality. Safety data showed that adding PD1i to asparaginase-based chemotherapy resulted in an expected increase in hematologic toxicities, but with a reduced risk of severe/fatal infections and rare severe immune-related adverse events. The authors conclude that frontline PD1i, particularly in combination with asparaginase, yielded significantly improved outcomes with a manageable safety profile in ENKTL.