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Novel Treatment of Burkitt Lymphoma with Dose-Adjusted EPOCH-Rituximab: Preliminary Results Showing Excellent Outcome.

Kieron Dunleavy, Stefania Pittaluga, John Janik, Nicole Grant, Margaret Shovlin, Richard Little, Robert Yarchoan, Seth Steinberg, Elaine S. Jaffe and Wyndham H. Wilson

Abstract

Burkitt Lymphoma (BL) is a highly proliferative lymphoma with a propensity to present in extranodal sites. Standard treatment for BL involves intensive, multi-agent chemotherapy that is highly effective but associated with considerable toxicity and treatment-related mortality, particularly in older patients. Based on the observation that DA-EPOCH overcomes the adverse effect of high proliferation in diffuse large B-cell lymphomas, we hypothesized it may be effective in BL. We have undertaken a study of DA-EPOCH-Rituximab in untreated BL in an attempt to maintain a high cure rate with low treatment related toxicity. Eligible patients had untreated BL and could be HIV positive or negative. HIV negative patients (n=13) received 6 cycles of DA-EPOCH-R as previously described (Blood 99: 2685, 2002). Patients with HIV-associated BL (n=4) received 3–6 cycles of DA-EPOCH-R for 1 cycle beyond CR for a minimum of 3 cycles. All patients received intrathecal methotrexate prophylaxis and therapy was administered in the outpatient clinic where possible. Characteristics of 17 patients include median age (range) 27 (18–66) and ECOG PS 1 (1–3); stage III/IV 9 (53%); LDH > N 9 (53%); male sex 13 (76%) and; extranodal sites 11 (65%). All 11 (65%) patients with extranodal disease had abdominal or pelvic involvement at diagnosis. No patients had central nervous system disease on presentation. Response is CR/CRu in 100% of patients. One patient received consolidative radiotherapy to a single site of residual disease. At a median potential follow-up of 28 months, OS and PFS are both 100% and EFS is 92.3%. Significant toxicities include fever/neutropenia in 16%, grade 4 neutropenia in 47% and grade 3/4 thrombocytopenia in 22% of cycles. There were no treatment related deaths and no tumor lysis syndrome. In conclusion, DA-EPOCH-R appears to be highly effective with relatively low toxicity compared to standard intensive high-dose regimens for BL. Infusional chemotherapy may reduce or eliminate the risk of tumor lysis syndrome. Accrual continues.