Combination Chemotherapy with Rituximab, Gemcitabine, Vinorelbine and Liposomal Doxorubicin As a Salvage Regimen for Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma

Standard chemotherapy with R-CHOP has a cure rate of approximately 60% for diffuse large B-cell lymphoma (DLBCL). Salvage therapy followed by autologous stem cell transplantation can cure 40–50% of patients. For patients who relapse following high dose therapy, salvage regimens are incurable. Combination therapy with rituximab, gemcitabine, vinorelbine, and liposomal doxorubicin (R-GND) has been shown to be efficacious in the setting of Hodgkin Lymphoma. We present the results of R-GND therapy among pts with relapsed refractory DLBCL.

Patients treated with R-GND at Vanderbilt University Medical Center for DLBCL from January 2004 through December 2010 with R-GND regimen are presented. Clinical outcomes studied included response to therapy, overall mortality, and drug toxicities, in particular grade 3/4, including neutropenia, anemia, and opportunistic infection. Wilcoxon rank sum, chi square analysis, and Kaplan-Meier analysis were performed using SPSS-19 software.

Twenty one pts with relapsed large cell lymphoma following immuno-chemotherapy were treated with R-GND therapy. The median age of pts was 60.5 (range 24–81). Eleven pts were male. The cell of origin of DLBCL based on pathology was available on 13 patients. Ten were germinal center histogenic origin and 3 patients had DLBCL of non-germinal center origin. The median number of prior therapies was 2. Seven pts underwent prior autologous stem cell transplantation. Eight pts received prior radiation therapy. Six pts were stage II at initial diagnosis, 2 were stage III and 13 were stage IV. Rituximab 375mg/m², gemcitabine 1000 mg/m², vinorelbine at 100 mg/m² and liposomal doxorubicin 30mg/m² were administered on day 1 and day 8 of every 21 day cycle. Dose reductions were based on patient tolerability. Colony stimulating factors was used on day 9 of each cycle. Radiological studies were performed after 2 cycles or earlier if there was clinical suspicion for progression. The total number of cycles for all patients was 42 cycles. The major grade 3/4 toxicities were anemia in 42%, thrombocytopenia in 38%, neutropenia in 33%, infection in 14% and respiratory failure in 4% of patients. Objective responses were noted in 9 patients (42%). Three patients attained a complete response to therapy and 6 pts had a partial response or stable disease. The median progression free survival was 1.3 months. The median overall survival of all patients was 3.9 months. The three patients attaining a complete response had DLBCL of non-germinal center cell origin.

R-GND is an alternative regimen with an overall response rate of 42% among patients with relapsed diffuse large B cell lymphoma. The interesting observation of the 3 patients who attained a complete response were of non-germinal center origin of DLBCL warrants further exploration of the role of gemcitabine based combination treatment in large cell lymphoma.

No relevant conflicts of interest to declare.