Adding rituximab to combination chemotherapy for primary mediastinal B-cell lymphoma yields a high cure rate and may obviate the need for thoracic radiation therapy, a study has shown.
Patients in a single-group, prospective phase II study were treated with dose-adjusted etoposide, doxorubicin, cyclophosphamide with vincristine, prednisone, and rituximab (DA-EPOCH-R). All but 2 of the 51 adults with lymphoma in the study were able to forgo radiotherapy, and there were no recurrences during a median follow-up of 5 years, reported Dr. Kieron Dunleavy of the National Cancer Institute and his colleagues.
"These findings suggest that DA-EPOCH-R is a therapeutic advance for this type of lymphoma," they wrote (N. Engl. J. Med. 2013;368:1408-16 [doi:10.1056/NEJMoa1214561]).
In a previous study, Dr. Dunleavy and his colleagues found that DA-EPOCH yielded an overall survival of 79%. To examine whether the addition of rituximab would further improve outcomes, they enrolled treatment-naive patients who had masses of at least 5 cm and presented over a 13-year period.
The study patients’ median age was 30 years (range, 19-52 years), and 59% were women. Mediastinal B-cell lymphoma was advanced, with a median tumor diameter of 11 cm. Approximately 30% of patients had stage IV disease.
All 51 patients received six to eight cycles of DA-EPOCH-R. Two patients showed persistent focal disease after therapy, and one patient showed disease progression. Two of the patients then underwent mediastinal radiotherapy, and one underwent excisional biopsy. All three were disease free thereafter.
After follow-up, ranging from 3 to 156 months, overall survival was 97% and event-free survival was 93%, with no recurrences of the cancer, the investigators reported.
Primary mediastinal B-cell lymphoma develops in the thymus, "predominantly affects young women, is aggressive, and typically is manifested by a localized, bulky mediastinal mass, often with pleural and pericardial effusions," they noted. There have been few prospective studies of the disease; and the findings have been conflicting, so at present there are no treatment standards. Immunochemotherapy usually does not achieve tumor control. Mediastinal radiotherapy (associated with severe late adverse effects) after aggressive chemotherapy is the current regimen.
The toxic effects of the chemotherapy regimen were similar to other previously reported events. Neutropenia occurred during half of the chemotherapy cycles overall, thrombocytopenia occurred in 6%, and hospitalization was required for fever and neutropenia in 13% of the cycles. There were no significant cardiac toxic effects.
Dr. Dunleavy and his associates also reported the results of DA-EPOCH-R therapy in an independent retrospective cohort of 16 patients treated at Stanford (Calif.) University Medical Center during the past 5 years. All of the Stanford patients were able to forgo radiation therapy, and event-free survival was 100%.
An international trial of DA-EPOCH-R for treating children or adolescents with primary mediastinal B-cell lymphoma is currently underway (clinical trial number NCT01516567).
The study was supported by the National Cancer Institute. Amgen provided filgrastim for the study but had no involvement with study design or with data collection or analysis. The investigators reported having no relevant financial conflicts.