Dr Marouf on the Efficacy of PD-L1 Inhibition in R/R Extranodal NK/T-cell Lymphoma

Amira Marouf, MD, PhD student, medical faculty, Necker Hospital/Imagine Institute, Université Paris Cité, discusses the efficacy of PD-L1 inhibitors in relapsed/refractory extranodal natural killer/T-cell lymphoma (ENKTCL).

Although strategies for treating relapsed/refractory ENKTCL have improved, this population often experiences poor prognosis and could benefit from alternatives to standard-of-care asparaginase-containing regimens. PD-L1 upregulation has been implicated in ENKTCL pathogenesis, and PD-1 therapy has accordingly been identified as a potential strategy for this population.

A prospective study was conducted to assess the efficacy of single-agent pembrolizumab (Keytruda) vs nivolumab (Opdivo) or pembrolizumab in this disease setting. Patients had relapsed/refractory ENKTCL and had been previously treated with at least 1 cycle of salvage anti–PD-L1 therapy between 2017 and 2022. Thirty-seven patients across 24 French centers were enrolled onto the study, including 12 patients who had been prospectively evaluated in the ACSE Unicancer study and were given PD-L1 monotherapy. The cohort also included 25 patients with R/R ENKTCL who had real-life, retrospective data.

The study also involved a comparison of these patients with a historic cohort of 38 patients treated for relapsed/refractory ENKTCL prior to the advent of immunotherapy in this space. These patients had received at least 1 cycle of first salvage therapy without a PD-L1 inhibitor regimen between 2006 and 2019, as identified from the ENKTCL national observatory. All patients had previously received first-line asparaginase-containing regimens.

Comparative analysis after propensity score matching showed that patients in the anti–PD-1 cohort had improved OS vs those who received historic salvage therapy, but did not experience improved PFS, Marouf reports. This discrepancy in PFS and OS could be attributed to the association of chemotherapy to immunotherapy in subsequent salvage therapy administered to the PD-L1 inhibitor group, she explains.

These results confirm the superiority of immunotherapy regimens over historical salvage therapy., Marouf states. Next steps for this research include the investigation of PD-L1 therapy in the frontline for patients in this population, she adds. Future research should aim to increase the understanding of predictive factors of response and improve the identification of patients with ENKTCL who would benefit from PD-L1 inhibition, Marouf concludes.