Rituximab Dose Adjusted EPOCH Improves Progression-Free Survival of Patients Affected By Diffuse Large Cell Lymphomas with Double Expression of MYC and BCL2 Proteins

Introduction: A large portion ofdiffuse large B-cell lymphomas (DLBCL), ranging from 20% to 40%, has double expression of MYC and BCL2 proteins (DE). These lymphomas are characterized by high-risk gene signatures and poor prognosis, their optimal treatment has not been defined yet. Despite R-CHOP remains the standard of care for these patients, preliminary data suggested a high complete response rate following Dose Adjusted EPOCH plus Rituximab (R-DAEPOCH). Methods: In this study, we have analyzed the outcome of 100 patients with newly diagnosed of DE DLBCL [determined by immunohistochemical analysis (MYC expression ≥40% and BCL2 ≥ 50% of tumor cells)], treated in two Italian Hematological Departments. Thirty-four patients received 6 courses of R-DAEPOCH and their outcome was compared with a historical cohort of 66 patients treated with R-CHOP (n=46) or high-dose sequential therapy followed by autologous stem cell transplantation (R-HDS) (n=20). In terms of clinical characteristics, the median age were 58, 65 and 57 years respectively. Overall, 73 pts had an IPI score ≥ 2 and were equally distributed among cohorts (70%, 67%, 90%, respectively p=0.15). Cell of origin (COO) was defined according to Hans algorithm: overall 50 patients (50%) had activated B-cell subtype (ABC) with significantly more patients in R-DAEPOCH cohort (64%) as compared to the others (38% and 55%, p=0.04). Results: At a median follow-up of 20 months (6-170 months), the estimated 2 years PFS and OS for the entire population were 53% (95%CI, 40%-64%) and 77% (95%CI, 66%-85%), respectively. In the limited low risk group (IPI 0-1) the 2 years PFS and OS were 67% (95%CI,42%-83%) and 88% (95%CI, 59%-96%), respectively. An improved PFS was observed in pts treated with R-DAEPOCH as compared to R-CHOP (79% vs 41%, p=0.04), but no statistical difference was observed between R-DAEPOCH and R-HDS (79% vs 54%, p=0.16). In addition, primary refractory disease occurred in 12% of patients after R-DAEPOCH and in 24% following R-CHOP. The type of treatment did not influence OS (96% vs 69% vs 79%, p=ns). In the group of patients with low IPI we did not observe a significant difference in term of PFS between R-DAEPOCH and R-CHOP (87% vs 52%, p=0.30). Patients with ABC subtype had a significant better PFS when treated with either R-DAEPOCH or R-HDS as compared to R-CHOP (82% vs 63% vs 33%, p=0.04), in fact the median PFS of patients receiving R-CHOP was only 16.8 months. In patients identified with non ABC subtype, the type of treatment did not influence either PFS or OS. Conclusions: R-DAEPOCH and R-HDS improved PFS in patients affected by DE DLBCL. DE Patients with ABC profile seems to have an advantage when treated with R-DAEPOCH or R-HDS whereas a short time to treatment failure is observed when these patients receive R-CHOP.