A Cancer and Leukemia Group B multi-center study of DA-EPOCH-rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular subtype

Authors

Wyndham Wilson, National Cancer InstituteFollow
Sin-Ho Jung, Duke University Medical Center, Durham, NC
Pierluigi Porcu, Ohio State University Medical Center, Columbus, OH
David Hurd, Wake Forest University School of Medicine, Winston-Salem, NC
Jeffrey Johnson, Duke University Medical Center, Durham, NC
S. Eric Martin, Helen F. Graham Cancer Center, Newark, DE
Myron Czuczman, Roswell Park Cancer Institute, Buffalo, NY
Raymond Lai, University of Alberta, Edmonton, Alberta, Canada
Jonathan Said, University of California, Los Angeles,
Amy Chadburn, Northwestern University, Chicago, IL
Dan Jones, Quest Diagnostics Nichols Institute, Chantilly, VA
Kieron Dunleavy, National Cancer Institute, Bethesda, MD
George Canellos, Dana Farber Cancer Institute, Boston, MA
Andrew D. Zelenetz, Memorial Sloan Kettering Cancer Institute, New York, NY
Bruce D. Cheson, Georgetown University Medical Center, Washington
Eric D. Hsi, Cleveland Clinic, Cleveland, OH

Date of this Version

2011

Citation

Wilson WH, Jung S-H, Porcu P, Hurd D, Johnson J, Martin SE, Czuczman M, Lai R, Said

J, Chadburn A, Jones D, Dunleavy K, Canellos G, Zelenetz AD, Cheson BD, and Hsi ED for the

Cancer and Leukemia Group B. A Cancer and Leukemia Group B multi-center study of DAEPOCH-

rituximab in untreated diffuse large B-cell lymphoma with analysis of outcome by molecular

subtype. Haematologica 2012;97(5):758-765. doi:10.3324/haematol.2011.056531

Abstract

Background

A phase II trial of dose-adjusted etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin and rituximab (DA-EPOCH-R) from the National Cancer Institute showed promising activity in untreated diffuse large B-cell lymphoma. The Cancer and Leukemia Group B conducted a study to determine if these results could be reproduced in a multi-institutional setting.

Design and Methods

The study included 69 patients with untreated diffuse large B-cell lymphoma at least 18 years of age and at least stage II. Radiaton therapy was not permitted on study. Median age was 58 years (range 23-83) and 40% had high-intermediate or high International Prognostic Index risk. Immunohistochemical biomarkers for cell of origin and proliferation were performed.

Results

With a median follow up of 62 months, time to progression and overall survival were 81% and 84%, respectively, and time to progression was 87%, 92% and 54% for low/low-intermediate, high-intermediate and high International Prognostic Index risk groups, respectively, at 5-years and beyond. The time to progression and event-free survival of germinal center B-cell lymphoma were 100% and 94%, respectively, and non-germinal center B-cell GCB diffuse large Bcell lymphoma were 67% and 58%, respectively, at 62 months (germinal center vs. non-germinal center B cell P=0.008). DA-EPOCH-R was tolerated without significant grade 4 non-hematologic toxicities.

Conclusions

These results provide the first confirmation by a multi-institutional group that DA-EPOCH-R provides high durable remissions in diffuse large B-cell lymphoma and is effective in both germinal center and non-germinal center B-cell subtypes. The trial was registered at ClinicalTrials.Gov (NCT00032019)