Cyclophosphamide, Mitoxantrone Hydrochloride Liposome, Vincristine, and Prednisone Regimen with or without Rituximab (CMOP±R) Shows High Efficacy As a First-Line Treatment for Non-Hodgkin's Lymphoma: A Phase II Clinical Trial with Matching-Adjusted Indirect Treatment Comparison (MAIC) Analysis

Huang, Haiwen

Introduction: Non-Hodgkin's lymphoma (NHL) represents a significant challenge in hematology, with a high mortality rate despite advances in treatment strategies. Patients with elevated International Prognostic Index (IPI) scores frequently experience disease relapse or refractory disease. The CMOP regimen, comprising cyclophosphamide, mitoxantrone hydrochloride liposome, vincristine, and prednisone, has demonstrated efficacy in the treatment of newly diagnosed peripheral T-cell lymphoma (PTCL), as evidenced by the results of a recent study (Huang et al., ASH 2022 abstract 1632). Nevertheless, its efficacy in other NHL subtypes remains uncertain. The objective of this study is to evaluate the efficacy and safety of the CMOP±R regimen as a first-line therapy in patients with newly diagnosed NHL.

Methods: This prospective, single-arm, open-label, multicenter phase 2 study enrolled adult patients with newly diagnosed NHL. Patients received the CMOP±R regimen every four weeks for a maximum of six cycles, or until disease progression or the development of unacceptable toxicity. The primary endpoint was the objective response rate (ORR) after induction therapy. Secondary endpoints included the progression-free survival (PFS), and overall survival (OS). Unanchored MAIC with patient data weighted to match the aggregate baseline characteristics of the POLARIX trial (Tilly et al., NEJM 2022) was performed for comparative outcome analysis. Adverse events were classified according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. The study is registered at www.chictr.org.cn (ChiCTR2300074073).

Results: A total of 39 eligible patients were enrolled between December 7, 2022, and April 17, 2024. The median age of these patients was 59 years (range 32-76). Among them, 84.6% had advanced stage disease (stage III: 17.9%, stage IV: 66.7%), and 51.2% had an IPI score ≥3. At the interim analysis with a median follow-up of 9.0 months (range 0.3-19.3), 31 patients were eligible for best response assessment. Thirty patients achieved an objective response, yielding an ORR of 96.8%. Twenty-four patients achieved a complete response (CRR 77.4%). Four patients experienced disease progression. Four deaths were observed, including three patients of non-relapse mortality. The MAIC analysis in DLBCL patients showed that CMOP±R achieved a slightly improved response compared to the R-CHOP (weighted ORR 94.6% vs 83.8%, P=0.126; weighted CRR 82.2% vs 74.0%, P=0.485) or pola-R-CHP arm (weighted ORR 94.6% vs 85.5%, P=0.196; weighted CRR 82.2% vs 78.0%, P=0.721) from the POLARIX study. In subgroup analysis, patients with advanced IPI scores (3-5) showed a high ORR (100%) and CRR (87.5%). The ORR was 91.7% (11/12) in DLBCL and 100% (8/8) in PTCL. The CRR in patients with DLBCL and PTCL was 83.3% (10/12) and 75% (6/8), respectively. The most prevalent grade 3-4 treatment-related adverse events were leukopenia (25.6%), neutropenia (35.9%), and lymphopenia (41.0%). Anemia and thrombocytopenia were observed in 51.3% and 33.3% of patients, respectively, with low incidences above grade 3. Cardiac evaluations indicated normal left ventricular ejection fraction (median 63.5%, range 58.0%-72.0%) and creatine kinase MB levels. Additionally, there were no cases of atrial fibrillation or severe cardiac arrhythmias.

Conclusions: The CMOP±R regimen exhibited notable efficacy as a first-line treatment for NHL, particularly in patients with advanced-stage disease, while maintaining a manageable safety profile. Based on the MAIC results, CMOP±R is associated with a favorable response in patients with DLBCL.