PRELIMINARY RESULTS OF A PHASE 2 STUDY OF CHIDAMIDE, GEMCITABINE, VINORELBINE, AND MITOXANTRONE LIPOSOME (CHI‐GVM) IN RELAPSED/REFRATORY PERIPHERAL T‐CELL LYMPHOMA

Abstract

Introduction: Patients with relapsed or refractory peripheral T-cell lymphoma (R/R PTCL) have a poor prognosis. There is no effective treatment for these patients. Mitoxantrone hydrochloride liposome showed high antitumor activity and low toxicity in lymphoma. In a phase II clinical study of mitoxantrone hydrochloride liposome monotherapy for R/R T-cell lymphoma, the overall response rate (ORR) and complete remission rate (CRR) of PTCL, not otherwise specified (PTCL, NOS) reached 34.4% and 18.8%. Our study aimed to explore whether the combination chemotherapy regimen containing mitoxantrone liposomes can improve the efficacy and survival of R/R PTCL. Methods: A Phase II, multicenter, single-arm, open-label study is planned at our center. All patients enrolled are R/R PTCL and will receive induction therapy with chidamide (20 mg, twice a week), gemcitabine (1 g/m2, d1), vinorelbine (20 mg/m2, d1), and mitoxantrone hydrochloride liposome (20 mg/m2, d1) (Chi-GVM) for 2–4 cycles. Patients aged 60 years or younger with complete remission (CR) / unconfirmed complete remission (CRu) / partial remission (PR) after 2–4 cycles of induction therapy received autologous stem cell transplantation (ASCT) prior to maintenance therapy. Patients after ASCT or patients over 60 years old with CR/CRu/PR receive maintenance therapy of chidamide (20 mg twice a week) until intolerance or disease progression (PD). Efficacy was assessed by contrast-enhanced CT or PET-CT every 2 cycles during treatment. The primary endpoint of the study was ORR and secondary endpoint was duration of remission (DOR) and1-year progression-free survival (1y-PFS). Results: A total of 7 patients were treated with Chi-GVM between September 2022 and February 2023, including 3 patients with PTCL, NOS; two patients with ALK negative anaplastic large cell lymphoma (ALCL, ALK-); and 2 patients with monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). Five male and two female were included, with a mean age of 57 years, and one patient was post-ASCT. Two patients were re-staged of stage I–II and five of stage III–IV prior to treatment, extranodal lesions including stomach, skin and intestinal. Four patients were evaluable for efficacy, 1 patient was lost to follow-up, and 2 patients did not reach the assessment time. Of the evaluable patients, 2 patients had a best response of CR and 2 patients experienced PD, one patient achieved CR and received consolidation therapy with ASCT. Grade 2 or 3 adverse events occurred in 5 patients, including 3 cases of leukopenia, 4 cases of neutropenia, 2 case of thrombocytopenia, and 1 case of hepatic insufficiency. One patient had myocardial damage before treatment, and kept stable after mitoxantrone hydrochloride liposome used. Keywords: Aggressive T-cell non-Hodgkin lymphoma, Chemotherapy, Late Effects in Lymphoma Survivors No conflicts of interests pertinent to the abstract.