Latest Update Results of Cmoep Regimen in Treatment-Naive Patients with Peripheral T-Cell Lymphoma
Authors: Yu Jingwei , Sun Xiuhua , Gao Guangxun , Yu Li , Wang Jiesong , Qiu Lihua , Qian Zhengzi , Li Wei , Zhang Huilai 
Published: December 2024

Background:

Peripheral T-cell lymphoma (PTCL) is a heterogeneous and aggressive group of lymphoma, representing 25%~30% of non-Hodgkin lymphomas in China. The standard initial treatments for PTCL include CHOP or CHOEP, but the long-term survival is suboptimal. At the 2024 EHA annual meeting (Abstract PB3009), preliminary efficacy and manageable safety of Mitoxantrone hydrochloride liposome (Lipo-MIT) combined with cyclophosphamide, vincristine, etoposide and prednisone(CMOEP) regimen in treatment-naive(TN)-PTCL were reported, showing an objective response rate (ORR) of 100% and a complete response (CR) rate of 50%. This update provides the most recent data on CMOEP in TN-PTCL.This phase I study (NCT05458180) aimed to explore the maximum tolerated dose (MTD) and recommended phase 2 dose (RP2D) of Lipo-MIT in the CMOEP regimen.

Methods:

Pts (18-65 years of age) with TN-PTCL were eligible. Lipo-MIT was administered on day 1 at three dosage levels (DL1: 15 mg/m2, DL2: 18 mg/m2, DL3: 20 mg/m2), cyclophosphamide was given on day 1 at 750 mg/m2, vincristine at 1.4 mg/m2 (with maximum dose of 2 mg) on day 1, etoposide at 60 mg/m2 on days 1-3, and prednisone at 100 mg on days 1-5 of each cycle. The treatment cycle was repeated every 21 days. And up to 6 cycles of therapy were planned. In the first cycle, dose-limiting toxicity (DLT) was assessed to determine the MTD of Lipo-MIT in the CMOEP regimen. The primary endpoint was to determine the MTD. Secondary endpoints were DLT, CR rate, ORR, progression-free survival (PFS), overall survival(OS) and safety. Adverse events (AEs) were documented according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.

Results:

Between August 30, 2022 and March 14, 2024, the study had enrolled 13pts (DL1: n=3, DL2: n=7, DL3: n=3), including 3 with angioimmunoblastic T-cell lymphoma (AITL), 4 with PTCL-NOS, 2 with ALK negetive anaplastic large cell lymphoma (ALCL), 1 with ALK positive ALCL, 1 with nodal TFH cell lymphoma of follicular-type, 1 with monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), and 1 with cutaneous T-cell lymphoma (CTCL). The median age was 52 years (range: 19-64 years), with 7 males (53.8%). 9(69.2%) pts were in stage III-IV, IPI score 3-5 with 1 (7.7%) pts , and 5(38.5%) pts presented with B symptom.

During the study, no DLTs occurred. The most common ≥grade 3 treatment-related adverse events (TRAEs) with an incidence ≥10% were leucopenia (76.9%), neutropenia (76.9%), lymphocytopenia (38.5%), anemia (38.5%), thrombocytopenia (15.4%) and pneumonia (15.4%). At the data cutoff, 12 pts had undergone at least one efficacy assessment, showing an ORR of 100% (12/12) and a CR rate of 66.7% (8/12). With a median follow-up of only 2.6 months, mPFS and mOS will be demonstrated after a longer follow-up. Considering the elevated hematologic toxicity observed after multiple treatment cycles and taking into account the preliminary efficacy data, Lipo-MIT 18mg/m2 was established as the RP2D.

Conclusions:

The CMOEP regimen exhibited manageable safety and encouraging efficacy in pts with TN-PTCL. A single-arm, multi-center, phase II study (NCT06433362) with dose expansion at RP2D is ongoing.