Low-Intensity Therapy Effective in Adults With Sporadic or Immunodeficiency-Associated Burkitt’s Lymphoma
In a study reported in The New England Journal of Medicine, Dunleavy et al assessed low-intensity treatment in adults with sporadic or immunodeficiency-associated Burkitt’s lymphoma. They found that low-intensity EPOCH-R (etoposide, doxorubicin, cyclophosphamide, vincristine, and prednisone plus rituximab [Rituxan])-based treatment produced high rates of durable response.
Study Details
The study involved 30 consecutive patients with untreated Burkitt’s lymphoma with (n = 11) or without (n = 19) human immunodeficiency (HIV) infection. Patients in the HIV-negative group received a standard dose-adjusted EPOCH-R regimen, and those in the HIV-positive group received a lower-dose short-course combination with a double dose of rituximab (EPOCH-RR). Patients in the dose-adjusted EPOCH-R group received two cycles after complete remission, for a total of six to eight cycles. Patients in the lower-dose short-course EPOCH-RR group received one cycle after complete remission, for a minimum of three and a maximum of six cycles. HIV-positive patients did not receive antiretroviral therapy during chemotherapy.
Among all patients, median age was 33 years (40% ≥ 40 years), 73% had intermediate-risk disease, and 10% had high-risk disease. HIV-infected patients were older and had higher-risk disease than HIV-negative patients. The HIV-positive patients had a median CD4-positive T-cell count of 322/mm3 (range, 32–835/mm3), and four had not previously received antiretroviral therapy.
Treatment Outcomes
The median cumulative doses of doxorubicin/etoposide and cyclophosphamide were 47% and 57% lower in the lower-dose short-course EPOCH-RR group than in the dose-adjusted EPOCH-R group. Median follow-up was 86 months in the dose-adjusted EPOCH-R group and 73 months in the lower-dose short-course EPOCH-RR group.
At median follow-up in each group, freedom from progression and overall survival rates were 95% and 100% in the dose-adjusted EPOCH-R group and 100% and 90% in the lower-dose short-course EPOCH-RR group; among 13 patients with an immunodeficiency-associated disease variant (ie, the 11 HIV-positive patients and 2 dose-adjusted EPOCH-R patients with primary immunodeficiencies), the respective rates were 92% and 92%.
No patients had recurrence of disease or died from Burkitt’s lymphoma. One patient with primary immunodeficiency-associated disease did not have a pathologic complete response and received localized radiotherapy. One HIV-positive patient developed acute myeloid leukemia 2.5 years after lower-dose short-course EPOCH-RR treatment and died 4 months later.
Adverse Effects
Fever and neutropenia requiring hospitalization occurred during 22% of the cycles in the dose-adjusted EPOCH-R group, including 7% of cycles in patient aged ≥ 40 years, and in 10% of cycles in the lower-dose short-course EPOCH-RR group, including 8% of cycles in those aged ≥ 40 years. Thrombocytopenia (nadir < 50,000/mm3) occurred during 6% and 13% of cycles.
Grade 3 gastrointestinal adverse events occurred in 8% and 14% of cycles, and grade 3 sensory impairment occurred in 21% and 9% of cycles. Tumor lysis syndrome developed in one patient in the lower-dose short-course EPOCH-RR group. No treatment-related deaths occurred. Mean CD4-positive T-cell count in HIV-infected patients decreased from 325/mm3 to 219/mm3 immediately after treatment (P = .03).
The investigators concluded, “In this uncontrolled prospective study, low-intensity EPOCH-R–based treatment was highly effective in adults with sporadic or immunodeficiency-associated Burkitt’s lymphoma…. Two confirmatory trials of risk-stratified treatment that are based on the [lower-dose short-course EPOCH-RR] and [dose-adjusted EPOCH-R] regimens are under way in adults (NCT01092182) and children (NCT01760226) with Burkitt’s lymphoma.
Wyndham H. Wilson, MD, PhD, of the National Cancer Institute, was the principal investigator for the study.
The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit www.nejm.org.
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