Favourable outcomes of poor prognosis diffuse large B-cell lymphoma patients treated with dose-dense Rituximab, high-dose Methotrexate and six cycles of CHOP-14 compared to first-line autologous transplantation

Abstract

The optimal therapeutic approach for young diffuse large B-cell lymphoma (DLBCL) patients with high-intermediate and high-risk age-adjusted international prognostic index (aaIPI) remains unknown. Hereby we report a 10-year single-centre study of 63 consecutively treated patients. To optimize outcome, two approaches were carried out: Cohort 1 patients received four cycles R-CHOP-21 (rituximab, cyclophosphamide, daunorubicin, vincristine, prednisolone over 21 days) followed by first-line high-dose chemotherapy with autologous stem-cell support (HDCT-ASCT), resulting in 2-year progression-free (PFS) and overall survival (OS) of 60·6% and 67·9%. 39·4% of those patients were not transplanted upfront, mainly due to early progressive disease (24·2%). Cohort 2 patients received an early intensified protocol of six cycles of CHOP-14 (cyclophosphamide, daunorubicin, vincristine, prednisolone over 14 days) with dose-dense rituximab and high-dose methotrexate resulting in promising overall response- (93·3%) and complete remission (90%) rates and sustained survival (2-year PFS and OS: 93·3%). In an intention-to-treat analysis, 2-year PFS (60·6% vs. 93·3%, hazard ratio [HR] 7·2, P = 0·009) and OS (69·7% vs. 93·3%, HR 4·95, P = 0·038) differed significantly, in favour of the early intensified protocol (Cohort 2). In a multivariate Cox-regression model, PFS (HR 8·12, 95% confidence interval [CI] 1·83–35·9, P = 0·006) and OS (HR 5·86, 95% CI 1·28–26·8, P = 0·02) remained superior for Cohort 2 when adjusted for aaIPI3 as the most important prognostic factor. Survival of young poor-prognosis DLBCL patients appears superior after early therapy intensification.