Introduction
Anti-PD1 immunotherapy has shown encouraging albeit modest efficacy in relapsed/refractory peripheral T-cell lymphoma (R/R PTCL) and NK/T-cell lymphoma (NKTL), achieving response rates of approximately 30% and 60%, respectively. Recent studies suggest that PARP inhibitors in tandem with anti-PD1 immunotherapy may exhibit therapeutic synergism.
Methods
Patients aged ≥18 years with R/R PTCL and NKTL after ≥1 prior line of systemic chemotherapy, including PD-1/PD-L1 inhibitors, were enrolled into this single-arm, open label phase 2 study (NCT06160843). Pembrolizumab was administered 200mg intravenously on day 1 plus olaparib taken 300mg oral twice daily, repeated in 21-day cycles, continued until disease progression or unacceptable toxicity.
Objectives
The primary endpoint of the study was objective response rate (ORR).
Results
As of 22nd October 2025, 10 patients have been enrolled; 7 were ongoing treatment while 3 had discontinued due to disease progression. Histological subtypes included PTCL with T-follicular helper phenotype (n=4), extranodal NKTL (n=2), and others (n=4). Five patients had completed ≥4 cycles and were evaluable on PET/CT for response assessment, with an ORR of 60.0% (PTCL-TFH, AITL, and PTCL-NOS, n=1 each) and complete response rate of 40.0%. One patient with NKTL achieved stable disease, accompanied by resolution of symptoms and plasma Epstein-Barr virus DNA. Grade 3 treatment-emergent adverse events were manageable and reported in 30.0% of patients, including anemia, hypokalemia, hematuria and hypocortisolism.
Conclusions
At interim analysis, pembrolizumab plus olaparib combination demonstrated promising efficacy with a manageable safety profile in R/R PTCL and NKTL. The trial is ongoing and the final data will be presented upon study completion.
