17th International Conference on Malignant Lymphoma, Palazzo dei Congressi, Lugano, Switzerland, 13 - 17 June, 2023.

Abstract

Introduction: Peripheral T-cell lymphoma (PTCL) is a heterogeneous disease with dismal outcomes. Standard CHOP (Cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy is still the most widely used regimen for front-line management. To explore new targeted drugs in PTCL, we conducted a phase 2, multi-center, non-randomized clinical trial, comparing the efficacy and safety of targeted agents combined with CHOP (CHOPX) with CHOP in newly diagnosed patients with PTCL. Methods: The primary outcome was complete response rate (CRR) at the end of treatment (EOT). Patients with newly diagnosed PTCL had enough tumor tissue for next generation sequencing (NGS) and were assigned to CHOPX and CHOP group based on investigators’ discretion. Patients in CHOPX group received intravenous cyclophosphamide 750 mg/m2, doxorubicin 50 mg/m2, and vincristine 1.4 mg/m2 (up to a maximum of 2 mg) on day 1, and oral prednisone 60 mg/m2 (up to a maximum of 100 mg) on day 1–5 every 21 days at the first cycle. X (i.e., targeted agent) was added from the second to sixth cycles as following, intravenous decitabine 10 mg/m2 on day -5 to -1 if with TP53 mutation. Subcutaneous azacytidine 100 mg on day −7 to −1 if with TET2/KMT2D mutation. Oral chidamide 20 mg on day1, 4, 8, 11 if with CREBBP/EP300 mutation. Oral lenalidomide 25 mg on day 1–10 if without above mutations. Patients in control group received standard CHOP regimen for 6 cycles. Analysis of efficacy and safety was of the intent-to-treat population. The study was registered with ClinicalTrials.gov, number NCT04480099. Results: Between 20 June 2020 and 22 September 2022, 108 patients were assessed for eligibility in the study. Ten patients met exclusion criteria and 2 patients withdrew informed consent before treatment. Forty-eight patients in the CHOPX group and 48 patients in the CHOP group were included into intent-to-treatment population. Baseline patient characteristics like age, gender, Ann Arbor stage, performance status, prognostic risk group was comparable between CHOPX and CHOP groups. The most common pathological subtypes were angioimmunoblastic T-cell lymphoma (67% vs. 60%), PTCL-not otherwise specified (17% vs. 21%), anaplastic T-cell lymphoma (6% vs. 8%) in the CHOPX and CHOP groups. As of 1 February 2023, 91 patients completed response evaluation at EOT. CRR in the CHOPX group was higher than the CHOP group (58% [25/43] vs. 33% [16/48]). The most common grade 3–4 hematological adverse events in CHOPX group were neutropenia (61%) and febrile neutropenia (27%). Conclusions: Preliminary analysis showed targeted agents combined with CHOP was effective and safe compared with standard CHOP in PTCL. Therapeutic strategy specifically towards molecular features may change current PTCL management in front-line setting. Keywords: combination therapies, molecular targeted therapies No conflicts of interests pertinent to the abstract.