Chidamide with Azacitidine and CHOP Treatment Plus Autologous Transplantation,Followed By Maintenance with Chidamide for Patients with Newly Diagnosed Peripheral T-Cell Lymphoma: Interim Analysis of a Prospective,Single Center,Single-Arm, Phase 2 Trial

Background: The standard first-line treatment for peripheral T-Cell Lymphoma (PTCL) is cyclophosphamide, doxorubicin, vincristine, and prednison (CHOP)，but the treatment effect is poor,the 5-year overall survival(OS) was only 30-40%.We aimed to evaluate the efficacy and safety of chidamide with azacitidine and CHOP treatment plus autologous stem-cell transplantation and of maintenance treatment with chidamide in newly diagnosed peripheral T-Cell Lymphoma (PTCL).

Methods: This is an ongoing prospective,single center，single-arm, phase 2 trial. We enrolled newly diagnosed PTCL patients (NK/T lymphoma and ALK positive T cell lymphoma were excluded )and used 21-day Chi+AZ-CHOP regimen for induction therapy.Subjects received CHOP on day 1 combined with azacitidine 100mg was subcutaneous injected daily for 5 days and oral chidamide 20mg two times per week of each cycle. 17 subjects received PEG-rhG-CSF Supportive care after treatment.These subjects who evaluated PR or CR remission after 4 to 6 courses of induction therapy will perform autologous hematopoietic stem cell transplantation(ASCT), followed by oral chidamide 20mg two times per week maintance. The primary endpoints is ORR per 2014 IWG criteria.Secondary endpoints include CR, safety and survival.

Results:From 3/2021 to 7/2023, 35 subjects with previously untreated PTCL were enrolled in chongqing university cancer hospital, and the study met its accrual.At study entry, 22 patients (62.8%) were angioimmu-noblastic T-cell lymphoma(AITL),4 patients (11.4%) was monomorphic epitheliotropic intestinal T-cell lyphomas(MEITL),3 patients (8.6%) were Peripheral T Cell Lymphoma, Not Otherwise Specified（PTCL-nos），2 patients (5.7%) was Mycosis fungoides(MF),4 patients(11.4%) was anaplastic large cell lymphoma; ALK-negative（ALCL-ALK).The median age was 55 years (range 27-70),and the M:F ratio was 1.5:1. 26 patients (74.3%) had stage Ⅲ/Ⅳ disease, 6 (17.1%) had bone marrow involvement, and 11 (31.4%) had IPI 3-5.By July 2023, 3 subjects did not return to the hospital for further treatment after the first cycle. 32 subjects received Chi+AZ-CHOP regimen treatments at least 2 cycles,median treatment cycles were 4 cycles. 2 subjects progressed during the treatment, 10 subjects were performed with autologous hematopoietic stem cell transplantation. The ORR was 87.5% with CR at 46.9%(n=32) .The assessment after autologous hematopoietic stem cell transplantation(n=10), ORR was 100 % and CR was 90%.To date, Evaluation of outcomes in patients with AITL at the end of induction(n=17), ORR was 94.1% and CR was 52.9%. Treatment was generally well tolerated with expected side exects.The most common grade 3-4 hematologic adverse events were neutropenia（45%），febrile neutropenia (40%)，anemia (25%) and thrombocytopenia (15%) ,Grade 3-4 non-hematologic toxicities included hypokalemia（35%）,nausea(30%), vomiting (20%),fatigue (30%),and elevated ALT (4.8%).No treatment-related deaths have been studied so far.

C onclusion: This trail proved that chidamide combined with azacytidine +CHOP is feasible and safe in the treatment of peripheral T-cell lymphoma. Especially，achieved a high CR rate in the induction therapy phase of AITL subtype. Although neutropenia is the most common adverse reaction, it is generally safe and controllable.