Gemox-Vinorelbine as Pre-Transplant Salvage in Diffuse Large B Cell Non-Hodgkin Lymphoma Patients Single Institutional Prospective Phase II Study

Abstract

Background: Salvage chemoimmunotherapy is given to determine the chemosensitivity of relapsed/refractory disease and to reduce the burden of disease prior to transplantation. There is no consensus regarding an optimal salvage regimen for all transplant-eligible patients, and the preferred approach varies by institution and clinician. Salvage chemoimmunotherapy comprises a combination of relatively high doses of non-cross-resistant drugs together with a monoclonal antibody against CD20 (eg, rituximab) and there is a trend towards selecting salvage regimen based on pathologic features of disease either germinal center DLBCL or Activated B-cell (ABC) DLBCL. Gemcitabine/oxaliplatin (GemOx), with or without rituximab, is a frequently used treatment of relapsed or refractory (r/r) aggressive B-cell non-Hodgkin lymphoma (B-NHL), and is NCCN -listed for transplant-eligible patients. Vinorelbine (vinca alkaloid) is a mitotic inhibitor which has shown encouraging early results in the treatment of heavily pre-treated relapsed or refractory lymphoma. In this study we explored the value of addition of vinorelbine(navelbine) to GemOx regimen in inducing more Complete remission (CR) in relapsed or refractory non-Hodgkin lymphoma.Aim: we investigated the efficacy and safety of Gemox-vinorelbine protocol as a pre-transplantation regimen in refractory and relapsed non Hodgkin lymphoma diffuse large B-cell type either Germinal Center B-cell or activated (ABC) B-cell type. Methods: Treatment consists of gemcitabine at 600mg /m2 on days 1 and 2, oxaliplatin 60 mg/m2 on days 1 and 2, vinorelbine 20mg/m2 d1 and dexamethasone 16mg/m2 d1-d4 repeated every 2 weeks d1, d15 with addition of Rituximab (375mg/m2) according to institute policy. Eligible patients were relapsed/refractory (R/R) NHL. Patients were recruited from Oncology Center Mansoura University during the period between December 2020 and September 2022 with a minimum follow of 6 months. Assessment was performed after 2-4 cycles of treatment by PET-CT. Results: Forty-five eligible patients (31 males ,69%) were treated with Gemox-vinorelbine ,the median number of treatment cycles was 3 (1-6).At the 1^st re-evalution (after 2-4 cycles),forty one patients were eligible for treatment evalution,12 patients achieved complete remission(29.2%) , 10 patients achieved partial response(24.4%) , 3 patients had stable disease(7.3%) and 16 patients had progressive disease (39%).Patients who had partial response completed 2 more cycles (10 patients) ,4 of them achieved CR at 2^nd re-evaluation (after 6 cycles) and 6 had a progressive disease .At least 3 cycles are needed for CR. A total of 16 patients achieved CR (39%). Eleven Patients proceeded to ASCT and 5 patients were rejected for bone marrow transplantation for causes like antithrombin III deficiency, one relapsed after stem cell collection, one considered to be in CR1 by bone marrow transplantation team. Gemox-vinorelbine protocol didn’t affect Stem Cell harvesting nor engraftment. Any Grade toxicities were thrombocytopenia (66.6%), anemia (35.5%), neutropenia (33.3%), febrile neutropenia (15.5%)

Neuropathy (33.3%), mucositis (20%). Treatment related mortality occurred in one patient (NF progressed to septic shock).The median progression free survival (PFS) was 10.8 months and median OS was 12 months. Both PFS nor OS was affected by cell of origin of DLBCL either germinal Center (GC) or non-germinal center (non-GC). Significant predictors for OS were IPI, late relapse >12 months versus primary refractory and early relapse <12months and number of prior lines. Summary and conclusions: Gemox-vinorelbine had good activity as as a salvage regimen in R/R NHL(DLBCL) especially if used as 1^st salvage in transplantation candidate patients.