TY - JOUR
T1 - Multicenter Study of Risk-Adapted Therapy with Dose-Adjusted EPOCH-R in Adults with Untreated Burkitt Lymphoma
AU - Roschewski, Mark
AU - Dunleavy, Kieron
AU - Abramson, Jeremy S.
AU - Powell, Bayard L.
AU - Link, Brian K.
AU - Patel, Prapti
AU - Bierman, Philip J.
AU - Jagadeesh, Deepa
AU - Mitsuyasu, Ronald T.
AU - Peace, David
AU - Watson, Peter R.
AU - Hanna, Wahid T.
AU - Melani, Christopher
AU - Lucas, Andrea N.
AU - Steinberg, Seth M.
AU - Pittaluga, Stefania
AU - Jaffe, Elaine S.
AU - Friedberg, Jonathan W.
AU - Kahl, Brad S.
AU - Little, Richard F.
AU - Bartlett, Nancy L.
AU - Fanale, Michelle A.
AU - Noy, Ariela
AU - Wilson, Wyndham H.
N1 - Funding Information:
The study was coordinated by the Lymphoid Malignancies Branch of the National Cancer Institute, and the study sponsor was the Cancer Therapy Evaluation Program, with support from the Cancer Trials Support Unit (Data Supplement). Rituximab was provided by Genentech, which had no role in trial design or data interpretation. The study was registered at ClinicalTrials.gov (NCT01092182) and was conducted in accordance with the principles of the Declaration of Helsinki. The study was approved by local institutional review boards of participating institutions, and all patients signed informed consent forms. Investigators submitted data using centralized electronic databases. Data were analyzed and interpreted by the lead authors and made available to all authors. All authors approved the manuscript and vouch for the completeness and accuracy of the data and the fidelity of the trial to the protocol.
Funding Information:
The Cancer Therapy Evaluation Program and Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health provided funding for this study. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Nos. U10CA180888 and UG1CA233230, as well as the AIDS Malignancy Consortium Grant No. UMI CA121947. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank all the patients and their caregivers who participated in this clinical trial. Genentech provided rituximab for the following institutions: Dana-Farber Cancer Institute, Massachusetts General Hospital, and MD Anderson Cancer Center.
Funding Information:
The Cancer Therapy Evaluation Program and Lymphoid Malignancies Branch, National Cancer Institute, National Institutes of Health provided funding for this study. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Nos. U10CA180888 and UG1CA233230, as well as the AIDS Malignancy Consortium Grant No. UMI CA121947. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
Publisher Copyright:
© 2020 by American Society of Clinical Oncology..
PY - 2020/5/26
Y1 - 2020/5/26
N2 - PURPOSE Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma. METHODS We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated adult Burkitt lymphoma. Low-risk patients received three cycles without CNS prophylaxis, and high-risk patients received six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment if leptomeninges were involved. The primary endpoint was event-free survival (EFS), and secondary endpoints were toxicity and predictors of EFS and overall survival (OS). RESULTS Between 2010 and 2017, 113 patients were enrolled across 22 centers, and 98 (87%) were high risk. The median age was 49 (range, 18-86) years, and 62% were $ 40 years. Bone marrow and/or CSF was involved in 29 (26%) of patients, and 28 (25%) were HIV positive. At a median follow-up of 58.7 months, EFS and OS were 84.5% and 87.0%, respectively, and EFS was 100% and 82.1% in low- and high-risk patients. Therapy was equally effective across age groups, HIV status, and International Prognostic Index risk groups. Involvement of the CSF identified the group at greatest risk for early toxicity-related death or treatment failure. Five treatment-related deaths (4%) occurred during therapy. Febrile neutropenia occurred in 16% of cycles, and tumor lysis syndrome was rare. CONCLUSION Risk-adapted DA-EPOCH-R therapy is effective in adult Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed (funded by the National Cancer Institute; ClinicalTrials.gov identifier: NCT01092182).
AB - PURPOSE Burkitt lymphoma is an aggressive B-cell lymphoma curable with dose-intensive chemotherapy derived from pediatric leukemia regimens. Treatment is acutely toxic with late sequelae. We hypothesized that dose-adjusted etoposide, doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (DA-EPOCH-R) may obviate the need for highly dose-intensive chemotherapy in adults with Burkitt lymphoma. METHODS We conducted a multicenter risk-adapted study of DA-EPOCH-R in untreated adult Burkitt lymphoma. Low-risk patients received three cycles without CNS prophylaxis, and high-risk patients received six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment if leptomeninges were involved. The primary endpoint was event-free survival (EFS), and secondary endpoints were toxicity and predictors of EFS and overall survival (OS). RESULTS Between 2010 and 2017, 113 patients were enrolled across 22 centers, and 98 (87%) were high risk. The median age was 49 (range, 18-86) years, and 62% were $ 40 years. Bone marrow and/or CSF was involved in 29 (26%) of patients, and 28 (25%) were HIV positive. At a median follow-up of 58.7 months, EFS and OS were 84.5% and 87.0%, respectively, and EFS was 100% and 82.1% in low- and high-risk patients. Therapy was equally effective across age groups, HIV status, and International Prognostic Index risk groups. Involvement of the CSF identified the group at greatest risk for early toxicity-related death or treatment failure. Five treatment-related deaths (4%) occurred during therapy. Febrile neutropenia occurred in 16% of cycles, and tumor lysis syndrome was rare. CONCLUSION Risk-adapted DA-EPOCH-R therapy is effective in adult Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed (funded by the National Cancer Institute; ClinicalTrials.gov identifier: NCT01092182).
UR - http://www.scopus.com/inward/record.url?scp=85088635517&partnerID=8YFLogxK
U2 - 10.1200/JCO.20.00303
DO - 10.1200/JCO.20.00303
M3 - Article
C2 - 32453640
AN - SCOPUS:85088635517
SN - 0732-183X
VL - 38
SP - 2519
EP - 2529
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 22
ER -