In a phase II study reported in the Journal of Clinical Oncology, Roschewski et al found that risk-adapted dose-adjusted etoposide doxorubicin, cyclophosphamide, vincristine, prednisone, and rituximab (EPOCH-R) produced high event-free survival rates among high- and low-risk adult patients with previously untreated Burkitt lymphoma.

Study Details

The U.S. multicenter trial enrolled 113 patients between 2010 and 2017, including 98 high-risk (87%) and 15 low-risk patients. Patients had a median age of 49 years (62% ≥ 40 years); 29 (26%) had bone marrow or cerebrospinal fluid (CSF) involvement, and 28 (25%) were human immunodeficiency virus (HIV)-positive.

Risk-adapted treatment consisted of three cycles of dose-adjusted EPOCH-R without central nervous system (CNS) prophylaxis in low-risk patients and six cycles with intrathecal CNS prophylaxis or extended intrathecal treatment for leptomeningeal involvement in high-risk patients. The primary endpoint was event-free survival.

Event-Free Survival

Median follow-up was 58.7 months. Among all patients, 4-year rates were 84.5% for event-free survival and 87.0% for overall survival; event-free survival was 100% in low-risk patients and 82.1% in high-risk patients, with overall survival of 84.9% in high-risk patients.

Treatment was equally effective across age groups (4-year event-free survival of 81.1%, 87.5%, and 85.4% in 18­–39, 40–59, and ≥ 60 year groups; overall P = .77), HIV status (84.9% vs 84.5% for HIV-positive vs HIV-negative, P = 1.00), and International Prognostic Index risk groups (81.5% vs 88.2% for low-/low-intermediate vs high-intermediate/high, P = .29).

The most important variable associated with survival outcomes was cerebrospinal fluid (CSF) involvement. Among patients with high-risk disease, those with vs without CSF involvement had 4-year event-free survival of 45.5% vs 89.9% (P = .0004). Among high-risk patients with vs without involvement of peripheral blood, bone marrow, or CSF, rates were 58.6% vs 92.4% (P = .0001), and among high-risk patients without CSF involvement, rates were 66.7% vs 92.4% (P = .0086) for those with vs without bone marrow or peripheral blood involvement.

Toxicity

Grade 3 or 4 thrombocytopenia occurred in 96 (17%) of 562 treatment cycles in 111 patients and fever with neutropenia occurred in 89 (16%). Tumor-lysis syndrome occurred in 5 patients (5%), grade 3 or 4 mucositis occurred in 21 (19%), grade 3 or 4 sensory neuropathy occurred in 5 (5%), and grade ≥ 2 motor neuropathy occurred in 7 (6%). Treatment-related death occurred in five patients during therapy, with causes consisting of multisystem organ failure and/or sepsis during the first cycle in four patients and respiratory failure after four cycles in one.

The investigators concluded, “Risk-adapted dose-adjusted EPOCH-R therapy is effective in adult [patients with] Burkitt lymphoma regardless of age or HIV status and was well tolerated. Improved therapeutic strategies for adults with CSF involvement are needed.”

Wyndham H. Wilson, MD, PhD, of the Lymphoid Malignancies Branch, National Cancer Institute, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.