To assess the clinical outcome and the influence of biomarkers associated with apoptosis inhibition (Bcl-2), tumor proliferation (MIB-1) and cellular differentiation on the outcome with dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) infusional therapy in diffuse large B-cell lymphoma and analysis of germinal center B-cell (GCB) and post-GCB subtypes by immunohistochemistry.
Patients and Methods
Phase II study of 72 patients with untreated de novo DLBCL who were at least 18 years of age and stage II or higher. Radiation consolidation was not permitted.
Patients had a median age of 50 (range: 19-85) years and 40% had a high-intermediate or high International Prognostic Index (IPI). At five-years, progression-free (PFS) and overall survival (OS) were 79% and 80%, respectively, with a median potential follow-up of 54 months. PFS was 91%, 90%, 67% and 47%, and OS was 100%, 90%, 74% and 37%, for 0-1, 2, 3 and 4-5 IPI factors, respectively, at five-years. The Bcl-2 and MIB-1 biomarkers were not associated with PFS or OS. Based on DA-EPOCH historical controls, rituximab only benefited Bcl-2 positive tumors. Bcl-6 expression was associated with higher PFS whereas GCB exhibited a marginally significant higher PFS compared to post-GCB DLBCL.
DA-EPOCH-R outcome was not affected by tumor proliferation and rituximab appeared to overcome the adverse effect of Bcl-2. Bcl-6 may identify a biological program associated with a superior outcome. Overall, DA-EPOCH-R shows promising outcome in low and intermediate IPI groups. A molecular model of treatment outcome with rituximab and chemotherapy is presented.