Anti-PD-1 antibody (Tislelizumab) combined with gemcitabine and oxaliplatin for extranodal NK/T-cell lymphoma failing asparaginase: A multicenter phase II trial.

in European journal of cancer (Oxford, England : 1990) by Kaiyang Ding, Hailing Liu, Lixia Sheng, Jie Ma, Xiaohui Zhang, Hongming Huang, Wei Shi, Hongling Peng, Lei Cao, Wei Wu, Jianyong Li, Lei Fan

TLDR

  • A phase II study demonstrated promising results for Tisle-GemOx in patients with ENKTCL failing asparaginase, with a best complete response rate of 60% and manageable toxicities.
  • The study achieved its primary endpoint and provides a potential salvage therapy for this patient population.
  • Further long-term follow-up is necessary to evaluate the durability of the response and explore optimal maintenance strategies.

Abstract

Extranodal natural killer/T-cell lymphoma (ENKTCL) is almost always fatal after the failure of asparaginase. This phase II study aimed to investigate the efficacy and safety of tislelizumab combined with gemcitabine and oxaliplatin (Tisle-GemOx) in patients with ENKTCL failing asparaginase. Eligible patients received Tisle-GemOx as initial induction for 6-8 cycles at 21-day intervals. Responders continued tislelizumab maintenance every two months for two years. The primary endpoint was the best complete response rate (CRR). As of September 2023, 32 patients were enrolled in our study. Among the 30 efficacy-evaluable patients, the best CRR was 60 %, meeting the primary efficacy endpoint. With a median follow-up of 22.6 months, the median progression-free survival (PFS) was 7.4 months and the 1-year PFS rate was 46.4 %. Subgroup analyses showed that shorter PFS was associated with previous lines of chemotherapy ≥ 2 (P = 0.034) and concomitant hemophagocytic lymphohistiocytosis (P = 0.040). Pseudo-progression was observed in three patients (10 %). The most common grade ≥ 3 toxicities were lymphopenia (25 %) and anemia (15.6 %). Tisle-GemOx exhibits promising anti-tumor activity and manageable toxicities as a salvage therapy for ENKTCL failing asparaginase. Further long-term follow-up is necessary to evaluate the durability of the response with tislelizumab maintenance in this patient population.

Overview

  • The study investigated the efficacy and safety of tislelizumab combined with gemcitabine and oxaliplatin (Tisle-GemOx) in patients with extranodal natural killer/T-cell lymphoma (ENKTCL) failing asparaginase.
  • The primary endpoint was the best complete response rate (CRR), and the study recruited 32 patients, of whom 30 were efficacy-evaluable.
  • The study aimed to provide a promising salvage therapy for ENKTCL failing asparaginase, with a focus on tislelizumab maintenance in responders.

Comparative Analysis & Findings

  • The study achieved its primary endpoint, with a best complete response rate (CRR) of 60% in the 30 efficacy-evaluable patients.
  • The median progression-free survival (PFS) was 7.4 months, and the 1-year PFS rate was 46.4%.
  • Subgroup analyses revealed that shorter PFS was associated with previous lines of chemotherapy ≥ 2 (P = 0.034) and concomitant hemophagocytic lymphohistiocytosis (P = 0.040).

Implications and Future Directions

  • The study suggests that Tisle-GemOx exhibits promising anti-tumor activity and manageable toxicities as a salvage therapy for ENKTCL failing asparaginase.
  • Further long-term follow-up is necessary to evaluate the durability of the response with tislelizumab maintenance in this patient population.
  • Future studies could explore the optimal dosing and duration of tislelizumab maintenance to maximize the benefit for patients with ENKTCL.
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