Mitoxantrone hydrochloride liposome (Lipo-MIT) combined with rituximab, gemcitabine, dexamethasone, and cisplatin (R-GDPM) in Relapsed/Refractory diffuse large B-cell lymphoma: A multicenter, single-arm study

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is a highly aggressive subtype of non-Hodgkin lymphoma (NHL), with approximately 30%-40% of patients developing relapsed or refractory (R/R) disease. Current clinical management for R/R DLBCL primarily involves regimens such as GemOx, ICE, GDP, and MINE, administered with or without rituximab. The objective response rate (ORR) with these regimens typically ranges from 45% to 80%, indicating that therapeutic efficacy remains suboptimal and requires further improvement. Mitoxantrone hydrochloride liposome (Lipo-MIT) has demonstrated initial efficacy and safety in ongoing clinical studies for R/R DLBCL. This study aimed to evaluate the efficacy and safety of Lipo-MIT combined with rituximab plus GDP (R-GDPM) in patients with R/R DLBCL. Preliminary data from this study previously reported an ORR of 75% (ASH 2024, Abstract #6506). Herein, we present updated efficacy and safety analyses from an expanded patient cohort. Methods: Patient inclusion criteria were as follows: age ≥18 years, histologically confirmed R/R DLBCL according to the WHO classification, measurable disease per Lugano 2014 criteria, and an ECOG performance status score of 0–2. The R-GDPM regimen included rituximab 375 mg/m² (d0), gemcitabine 750-1000 mg/m² (d1,8), dexamethasone 20 mg (d1-4), cisplatin 75 mg/m² (d1), and Lipo-MIT 18–20 mg/m² (d1), administered every 3 weeks for 6-8 cycles, or until disease progression or unacceptable toxicity occurred. The primary endpoint was the ORR. Secondary endpoints included complete response rate (CRR), progression-free survival (PFS), duration of response (DoR), overall survival (OS), and safety. Results: As of March 7, 2025, 33 patients were enrolled. The median age was 62 years (range: 30–77 years), with 20 males (60.6%). Twenty-six patients (78.8%) had stage III–IV disease (stage III: 27.3%; stage IV: 51.5%), and 19 patients (57.6%) had an International Prognostic Index (IPI) score ≥3. Six patients (18.2%) presented with B symptoms. Twelve patients (36.4%) had the germinal center B-cell (GCB) subtype, and 21 patients (63.6%) had the non-GCB subtype. Twenty-nine patients (87.9%) were refractory, and 4 patients (12.1%) were relapsed. Twenty-five patients (75.8%) had received two prior lines of therapy, and 8 patients (24.2%) had received three prior lines. The median dose of Lipo-MIT administered within the regimen was 17.5 mg/m². At data cutoff, 30 patients were evaluable for efficacy. The ORR was 80% (24/30), and the CRR was 50% (15/30). Among patients who received ≥4 treatment cycles, the ORR was 100% (17/17) and the CRR was 82.4% (14/17). The most common grade 3–4 treatment-related adverse events (TRAEs) included leukopenia (48.5%), neutropenia (45.5%), thrombocytopenia (18.2%), and anemia (15.2%). No treatment-related deaths or cardiac adverse events occurred. Conclusion: The combination of Lipo-MIT with R-GDP demonstrated encouraging efficacy and a manageable safety profile in patients with R/R DLBCL. Further studies with continued follow-up are warranted to assess survival outcomes.