A prospective clinical study on the combination of anti-PD1 monoclonal antibody with lenalidomide and azacitidine for the treatment of relapsed/refractory peripheral T-cell lymphoma Free

To explore the efficacy and safety of the anti-PD1 monoclonal antibody combined with lenalidomide and azacitidine regimen in the treatment of relapsed/refractory peripheral T-cell lymphoma (R/R PTCL).

Our center has registered a single-arm Phase II prospective clinical trial (NCT05182957) aimed at exploring the efficacy and safety of anti-PD1 monoclonal antibody combined with lenalidomide and azacitidine in treating relapsed/refractory peripheral T-cell lymphomas (R/R PTCL). The primary endpoints are overall response rate (ORR) and complete remission rate (CR), while secondary endpoints include overall survival (OS), progression-free survival (PFS), and safety.

From January 2020 to March 2023, this study enrolled 31 patients with relapsed/refractory PTCL (R/R PTCL) who received anti-PD1 combined with lenalidomide and azacitidine therapy. Among them, 18 were male and 13 were female, with a median age of 67 (range: 23–73) years. Of the 31 patients, 17 had AITL, 7 had PTCL-NOS, 6 had NK/TCL, and 1 had ALK-ALCL; 17 were primary refractory, and 14 had relapsed, including 8 who relapsed after autologous stem cell transplantation. The median number of prior lines of therapy was 2 (range: 1–5). As of June 2023, the median follow-up time was 15.8 (range: 2.7–39.5) months. Among the 31 patients, 29 were evaluable for efficacy, with an ORR of 62.1% (CR: 37.9%, PR: 24.2%). The estimated 2-year PFS and OS rates were 67.4% and 73.4%, respectively. Regarding safety, among all treated patients, grade ≥3 severe adverse events (SAEs) included hematologic SAEs such as neutropenia (45.2%), anemia (25.8%), and thrombocytopenia (32.2%), as well as non-hematologic SAEs such as pulmonary infection (6.4%), liver function impairment (6.4%), and rash (3.2%). Next-generation sequencing (NGS) was performed on tissue samples from 17/31 patients, and 14/17 patients exhibited one or more mutations in epigenetic modifier genes such as RHOA, TET2, and DNMT3A. The ORR after treatment in these patients was 71.4%.

The anti-PD1 monoclonal antibody combined with lenalidomide and azacitidine regimen can serve as an effective salvage therapy for R/R PTCL, further improving the prognosis of patients with R/R PTCL, with manageable adverse effects. NGS testing suggests that patients with gene mutations such as RHOA, TET2, and DNMT3A are sensitive to this treatment regimen, providing some evidence-based rationale for further research.