Mitoxantrone hydrochloride liposome, gemcitabine, vinorelbine with or without anti-CD20 antibody (GVM±CD20) in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma: A prospective, multicenter, Phase Ⅱ study

Abstract Background: Platinum-based salvage chemotherapy is the most widely used treatment approach for relapsed or refractory aggressive non-Hodgkin lymphoma (R/R aNHL), with an objective response rate (ORR) of 42.0–63.5% and a complete response (CR) rate of 13.5-40.0%.We previously reported the efficacy and safety of a novel non-platinum-based salvage regimen—GVM±R (mitoxantrone hydrochloride liposome Lipo-MIT, gemcitabine, vinorelbine, with or without rituximab)—in R/R aNHL, demonstrating promising activity with an ORR of 66.7% and a CR rate of 50.0% (ESMO 2024, Abstract #833P). Based on these encouraging results, we initiated a phase II, multicenter, prospective study to further evaluate this regimen. Preliminary data from this ongoing trial are presented here. Methods: This phase II study enrolled patients aged 18-65 years with R/R aNHL who either failed ≥1 prior line of standard therapy or achieved only partial response (PR) after ≥4 treatment cycles (with biopsy confirmation required for Deauville score 4 patients). The treatment regimen consisted of Lipo-MIT (18 mg/m² on day 1), gemcitabine (800 mg/m² on days 1 and 8), and vinorelbine (20 mg/m² on days 1 and 8), administered with or without anti-CD20 antibody in 21-day cycles for up to 6 cycles. Responding patients were permitted to undergo ASCT consolidation therapy. The study's primary endpoint was ORR, with secondary endpoints including CR rate, progression-free survival (PFS), overall survival (OS), disease-free survival (DFS), and safety assessment. The trial was registered at www.clinicaltrials.gov as NCT06244368. Results: From February 5, 2024 to March 27, 2025, 68 patients with R/R aNHL were enrolled, including 47 with diffuse large B-cell lymphoma (DLBCL), 14 with peripheral T-cell lymphoma (PTCL), 4 with extranodal NK/T-cell lymphoma (NKTCL), 1 with Burkitt lymphoma, 1 with plasmablastic lymphoma, and 1 with mantle cell lymphoma (MCL). The median age was 57.0 years (range: 18-66), with 41 males (60.3%). Most patients presented with advanced-stage disease (stage III: 15 22.1%; stage IV: 37 54.4%), and nearly half (33 48.5%) had an International Prognostic Index (IPI) score of 3-5. The median number of previous lines of therapy was 1 (range: 1-6). Fifty-two patients (76.5%) were refractory to first-line therapy, and 55 (80.9%) were refractory to last-line therapy. As of the data cutoff on July 24, 2025, 52 patients had completed efficacy evaluation, showing an ORR of 71.2% (37/52) and a CR rate of 40.4% (21/52). Patients refractory to first-line therapy achieved an ORR of 64.1% (25/39) and a CR rate of 38.5% (15/39), while those refractory to last-line therapy showed an ORR of 65.9% (27/41) and a CR rate of 36.6% (15/41). All 68 patients were included in the safety analysis. The grade 3/4 treatment-related adverse events (TRAEs) with an incidence ≥5% included leucopenia (73.5%), neutropenia (67.6%), thrombocytopenia (44.1%), anemia (32.4%), lymphocytopenia (26.5%), febrile neutropenia (13.2%), and pneumonia (5.9%). Conclusion: The GVM±CD20 regimen exhibited encouraging efficacy in R/R aNHLs, including refractory cases. The most common treatment-related toxicities were hematologic adverse events, which were manageable with supportive care but required close monitoring. The phase II trial is currently ongoing.