Presenting “the first prospective study” of mediastinal gray zone lymphoma, researchers from the National Cancer Institute reported that DA-EPOCH-R (infusional dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine, prednisone, and rituximab (Rituxan) and filgrastim (Neupogen) in untreated mediastinal gray zone lymphoma produced event-free survival of 62% and overall survival of 74% at 59 months median follow-up.
“DA-EPOCH-R alone produced durable remissions in most patients indicating it is an effective treatment for these relatively resistant lymphomas,” the authors wrote. While the results of the trial, which involved 24 patients, were considered promising, “we cannot rigorously determine if DA-EPOCH-R is optimal treatment for [mediastinal gray zone lymphoma] given the limited number of cases and absent a randomized study design,” Wyndham H. Wilson, MD, PhD, and colleagues wrote in Blood.
Mediastinal gray zone lymphoma is extremely rare, the investigators noted, and has pathologic features intermediate between the more common types of mediastinal B-cell lymphomas, nodular sclerosis Hodgkin lymphoma and primary mediastinal B-cell lymphoma. “The indeterminate pathobiology of [mediastinal gray zone lymphoma] has led to uncertainty regarding therapeutic strategy, and its clinical characteristics and treatment have not been characterized,” the researchers wrote.
Study participants had a median age of 33 years (range, 14–59) years and 46% had mediastinal masses ≥ 10 cm. “All patients had histological and/or phenotypic features intermediate between [primary mediastinal B-cell lymphoma] and [nodular sclerosis Hodgkin lymphoma]. Usually, the tumors have a predominant morphology, which was either [primary mediastinal B-cell lymphoma]-like in 33% (8/24), or more frequently Hodgkin-like in 63% (15/24) of cases, and one case was classified as composite [nodular sclerosis Hodgkin lymphoma] and [primary mediastinal B-cell lymphoma],” the researchers noted.
“All patients responded with 19 complete and 5 partial remissions,” the investigators reported. Nine patients were diagnosed with active disease at a median of 3 months (range, 1–6) after completing therapy. Based on positron-emission tomography/computed tomography evaluation showing disease limited to the mediastinal area, all nine patients received involved-field salvage radiotherapy “and four are in continuous remission at 3, 73, 91, and 128 months,” according to the study report.
“The occurrence of treatment failure in one third of [mediastinal gray zone lymphoma] patients and the curative potential of salvage radiotherapy makes early identification of treatment failure important,” the authors noted. Indicators of worse outcome include low absolute lymphocyte count, the presence of tumor-associated dendritic/macrophage cells, and CD15 expression on the malignant cells.
Results of the study were compared to a cohort of patients with primary mediastinal B-cell lymphoma prospectively treated with DA-EPOCH-R. “Patient eligibility was identical for both groups except patients with [primary mediastinal B-cell lymphoma] were required to have a mediastinal mass at least 5 cm. Treatment and follow-up were identical in both groups,” the investigators stated. “Compared with [primary mediastinal B-cell lymphoma], [mediastinal gray zone lymphoma] patients were more likely to be male, express CD15, have lower expression of CD20 and to have a worse outcome.”
The trial was registered at ClinicalTrials.Gov (NCT00001337). ■
Wilson WH, et al: Blood. July 14, 2014 (early release online).