Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma

Abstract

Background: Primary mediastinal B-cell lymphoma is a distinct subtype of diffuse large-B-cell lymphoma that is closely related to nodular sclerosing Hodgkin's lymphoma. Patients are usually young and present with large mediastinal masses. There is no standard treatment, but the inadequacy of immunochemotherapy alone has resulted in routine consolidation with mediastinal radiotherapy, which has potentially serious late effects. We aimed to develop a strategy that improves the rate of cure and obviates the need for radiotherapy.

Methods: We conducted a single-group, phase 2, prospective study of infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R) and filgrastim without radiotherapy in 51 patients with untreated primary mediastinal B-cell lymphoma. We used results from a retrospective study of DA-EPOCH-R from another center to independently verify the outcomes.

Results: The patients had a median age of 30 years (range, 19 to 52) and a median tumor diameter of 11 cm; 59% were women. During a median of 5 years of follow-up, the event-free survival rate was 93%, and the overall survival rate was 97%. Among the 16 patients who were involved in the retrospective analysis at another center, over a median of 3 years of follow-up, the event-free survival rate was 100%, and no patients received radiotherapy. No late morbidity or cardiac toxic effects were found in any patients. After follow-up ranging from 10 months to 14 years, all but 2 of the 51 patients (4%) who received DA-EPOCH-R alone were in complete remission. The 2 remaining patients received radiotherapy and were disease-free at follow-up.

Conclusions: Therapy with DA-EPOCH-R obviated the need for radiotherapy in patients with primary mediastinal B-cell lymphoma. (Funded by the National Cancer Institute; ClinicalTrials.gov number, NCT00001337.).

Figure 1. Kaplan–Meier Estimates of Event-free and Overall Survival of Patients with Primary Mediastinal B-Cell Lymphoma Receiving DA-EPOCH-R, According to Study Group

DA-EPOCH-R was administered to 51 patients in a prospective trial at the National Cancer Institute (NCI), and to 16 patients in a retrospective trial at Stanford University. In the prospective NCI cohort, the event-free survival rate was 93% (Panel A) and the overall survival rate was 97% (Panel B) at a median follow-up of 63 months. In the retrospective Stanford cohort, the event-free and overall survival rates were both 100% (Panel C and Panel D, respectively) at a median follow-up of 37 months.

Figure 2. Cardiac Ejection Fraction after Treatment with DA-EPOCH-R in 42 Patients in the Prospective NCI Cohort

Patients’ ejection fractions are shown according to the cumulative dose of doxorubicin they received (Panel A) and the years since they underwent treatment (Panel B). Cardiac echocardiography was performed in 42 available patients, beginning in 2009. There was no significant difference in ejection fraction over dose or time, nor was there a significant interaction between dose or timing of treatment and the ejection fraction (P = 0.30 and P = 0.20, respectively).