PD-1 Blockade Shows Improved Outcomes in NK/T-Cell Lymphoma and NSCLC Studies

A multicenter Chinese study of 418 patients with previously untreated advanced-stage natural killer/T-cell lymphoma (NKTCL) found that adding anti-PD-1 antibody to P-GEMOX chemotherapy significantly improved outcomes compared to chemotherapy alone or with autologous stem cell transplantation (ASCT). The analysis included 135 patients in the immunochemotherapy group and 283 in the chemotherapy group from 15 centers between 2014 and 2023, with a median follow-up of 40.7 months.

The immunochemotherapy group achieved an objective response rate (ORR) of 89.6% versus 77.0% for chemotherapy alone, with complete response (CR) rates of 77.0% versus 50.5%. The 3-year progression-free survival (PFS) rate was 64.1% in the immunochemotherapy group compared to 40.7% in the chemotherapy group, while 3-year overall survival (OS) rates were 79.5% versus 60.8%.

In propensity score-matched analysis of patients achieving CR after induction (41 per group), the 3-year disease-free survival (DFS) rate was 72.6% for immunochemotherapy plus anti-PD-1 maintenance versus 50.9% for chemotherapy plus ASCT (p = 0.032). The 3-year OS rate was 91.5% versus 72.9% (p = 0.029).

Grade 3-4 neutropenia was more common in the immunochemotherapy group at 40.0% versus 20.8% in the chemotherapy group (p < 0.001). Grade 3-4 hematologic toxicities were prevalent during ASCT, whereas anti-PD-1 maintenance was well tolerated. Grade ≥3 non-hematologic adverse events during anti-PD-1 maintenance were rare.

In advanced non-small cell lung cancer (NSCLC), a retrospective cohort study examined PD-1 blockade rechallenge strategies after prior immunotherapy failure. The study included 33 patients who received PD-1 blockade plus chemotherapy, 31 who received PD-1 blockade plus anlotinib, and 63 patients treated with docetaxel monotherapy as a contextual reference cohort.

ORR and disease control rate (DCR) were 30.3% (95% CI: 15.6%-48.7%) and 84.8% (95% CI: 68.1%-94.9%) in the PD-1 plus chemotherapy cohort, 22.6% (95% CI: 9.6%-41.1%) and 80.6% (95% CI: 62.5%-92.5%) in the PD-1 plus anlotinib cohort, and 15.9% (95% CI: 7.9%-27.3%) and 54.0% (95% CI: 40.9%-66.6%) in the docetaxel cohort.

Median duration of response among responders was 6.9 months (95% CI: 0.7-13.1), 7.1 months (95% CI: 5.0-9.2), and 3.1 months (95% CI: 1.9-4.3), respectively. Median PFS was 7.0 months (95% CI: 0.7-13.3), 6.5 months (95% CI: 2.2-10.8), and 3.3 months (95% CI: 2.2-4.4), and median OS was 17.8 months (95% CI: 8.0-27.6), 16.8 months (95% CI: 13.9-19.7), and 9.5 months (95% CI: 4.8-14.2), respectively.

Any-grade treatment-related adverse events (TRAEs) occurred in 84.8%, 80.6%, and 81.0%, and grade ≥3 TRAEs were 42.4%, 41.9%, and 34.9%, respectively. No treatment-related deaths were observed.

Cemiplimab has gained traction as both a monotherapy and in combination with chemotherapy for advanced NSCLC. In patients with PD-L1 expression of at least 50%, cemiplimab monotherapy demonstrated a significant overall survival benefit in the phase 3 EMPOWER-Lung 1 trial (NCT03088540). In the phase 3 EMPOWER-Lung 3 trial (NCT03409614), cemiplimab combined with platinum-doublet chemotherapy improved overall survival across both squamous and nonsquamous histologies.

Pharmacists play a key role in ensuring that PD-L1 testing and molecular profiling are completed before immunotherapy initiation, especially in nonsquamous disease, where actionable mutations may alter first-line therapy. Delays in molecular testing continue to pose challenges in real-world practice, with insurance barriers complicating even interim treatment strategies. Liquid biopsy has emerged as a practical solution to expedite decision-making, though negative liquid biopsy results do not replace tissue testing.