Efficacy and Safety of a New Regime Containing PD1 Antibody and Pegaspargase for Advanced-Stage or Relapsed/Refractory Natural Killer/T Cell Lymphoma

Background: Patients with advanced-stage or relapsed/refractory (r/r) natural killer/T cell lymphoma (NKTCL) had a poor prognosis. The anti-programmed death 1 (PD-1) antibody has demonstrated satisfactory efficacy and good tolerance for r/r NKTCL. In this report, we present the efficacy and safety analysis of a new regimen containing dexamethasone, azacytidine, pegaspargase, and tislelizumab (named as DAPT) for advanced-stage or r/r NKTCL in a prospective multicenter phase II study. Methods: Patients with advanced-stage or r/r NKTCL, aged over 18 years, were eligible for participation. The DAPT regimen chemotherapy was administered as the protocol treatment, which included dexamethasone 10 mg on days 1-3, azacytidine 100 mg on days 1-5, pegaspargase 3,750 IU on day 1, and tislelizumab 200 mg on day 6. Cycles were repeated every 21 days. The primary endpoint was the overall response rate (ORR) . Results: A total of 39 eligible patients were enrolled. The median age of 52 years (range, 32 to 72 years) and with a male-to-female ratio of 2.42:1. Twenty-four (61.5%) patients had newly diagnosed disease with stage IV, while 15 (38.5%) had r/r disease. Among 31 patients with available response, the ORR and complete remission (CR) rates were 77.4% and 33.3% for the entire cohort, 84.2% and 63.6% for newly diagnosed stage IV disease, and 31.6% and 27.3% for r/r disease, respectively. Ten patients underwent autologous hematopoietic stem cell transplantation (ASCT). The median progression-free survival (PFS) was 7.3 months in patients who completed 6 cycles of DAPT therapy. Moreover, the median PFS were 14.0,3.6 and 2.6 months in patients who achieved CR, PR and non-response, respectively. The median PFS was longer in those who achieved ASCT than those who did not experience transplantation (11.5 vs. 2.6 months). The most common treatment-related adverse events were was neutropenia (63.4%), followed by elevated alanine aminotransferase (43.9%), decreased fibrinogen (39.0%) and hypofibrinogenemia (39.0%). The incidence of ≥3 treatment-related adverse events was 26.8%, which included neutropenia (n=8), immune-related rash (n=2), and drug-induced liver injury (n=1) .No treatment-related deaths were observed. Conclusion: The DAPT regimen chemotherapy is an effective and tolerable treatment for advanced-stage or r/r NKTCL. Keywords: Lymphoma; Extranodal NK-T-Cell; Immunotherapy; Therapeutics; Prognosis