RISK‐ADAPTED THERAPY IN ADULTS WITH BURKITT LYMPHOMA: UPDATED RESULTS OF a MULTICENTER PROSPECTIVE PHASE II STUDY OF DA‐EPOCH‐R

Background: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma, which occurs in children and less commonly in adults. Dose-intensive approaches developed for pediatric leukemia/lymphoma are highly curative, but are poorly tolerated in adults and patients with HIV. A single-center study of 30 patients showed that lower treatment intensity with infusional DA-EPOCH-R was highly curative and well tolerated in adults with sporadic or HIV-associated BL (N Engl J Med 2013; 369:1915-1925). To validate these results, we undertook a multicenter study of DA-EPOCH-R in adult BL and investigated if a risk-adapted approach could further reduce treatment toxicity. Methods: Patients with newly diagnosed BL, age 18 years or older and any HIV status were enrolled at 24 participating sites. Patients were considered low-risk (LR) if they had a normal LDH, ECOG performance status of 0 or 1, stage I or II disease, and no tumor lesion over 7 cm. All other patients were considered high-risk (HR). LR patients received 3 cycles of DA-EPOCH-R without intrathecal treatment. HR patients with negative brain MRI and negative CSF cytology/ flow cytometry received 6 cycles of DA-EPOCH-R with MTX 12 mg IT on days 1 and 5 during cycles 3-6 (8 total doses). HR patients with active CNS disease received 6 cycles of DA-EPOCH-R and concurrent MTX 12 mg IT twice weekly for 2 weeks past negative results (minimum of 4 weeks), followed by MTX 12 mg IT once weekly x 6, and MTX 12 mg IT monthly x 6. Results: 112 of 116 planned patients have been enrolled; 110 who completed at least 1 cycle of therapy are included in this analysis. Characteristics include median (range) age 48 (19-86) years with 53 (48%) patients aged 50 years or over and 29 (26%) patients aged 60 years or over; male sex 86 (78%); stage III or IV disease 76 (69%); elevated LDH 73 (66%); CNS involvement 11 (10%); HIV positive 29 (26%). The frequency of bone marrow disease is under evaluation. Thirteen (12%) and 97 (88%) patients were classified as LR and HR, respectively. There were 6 deaths in the HR arm not attributed to disease progression/relapse: 2 deaths due to infection, and 1 death each attributed to respiratory failure, second malignancy, myocardial infarction, and unknown. All other reported toxicities were expected toxicities of DA-EPOCH-R. With a median follow-up of 34 months, the progression-free survival (PFS) for all patients beyond 10.2 months is 84.6% (95% CI: 75.6-90.4%); time-to-progression (TTP) is 91.1% (95% CI: 82.8-95.4%) and overall survival is 84.7% (95% CI: 75.4-90.7%). Age (> 40y versus <40y) and HIV status did not impact survival (see table). PFS for LR patients was 100% and 82% for HR patients. Notably, only 1 patient who progressed after DA-EPOCH-R was successfully salvaged and is still alive. Keywords: Burkitt lymphoma (BL).