Long-Term Outcome for De Novo or Minimally Treated Burkitt-Type Lymphoma/Leukemia (BL/B-ALL) After Therapy with Hyper-CVAD and Rituximab
Authors: Thomas Deborah A. , O'Brien Susan , Cortes Jorge E. , Faderl Stefan , Wierda William G. , Garcia-Manero Guillermo , Jabbour Elias , Ferrajoli Alessandra , Verstovsek Srdan , Burger Jan A. , Garris Rebecca , Romaguera Jorge , Hagemeister Fredrick , Kantarjian Hagop 
Published: October 2019

Abstract
Abstract 1781
The outcomes for Burkitt-type lymphoma/leukemia have improved significantly with the use of short, intensive, multi-agent chemotherapy regimens. The hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high dose methotrexate (MTX) and cytarabine) was established as an effective first line program for younger patients with de novo B-ALL [Thomas D, J Clin Oncol 17:2461, 1999]. Although the overall complete remission (CR) rate was 81%, the induction mortality rate was 19% for those at least 60 yrs of age (related to systemic fungal infections), reduced to < 5% with use of laminar air flow rooms since 1999. The 3-yr survival (OS) rate for older pts was 17% compared with 77% in younger pts. Standard dose rituximab was incorporated into the hyper-CVAD regimen (375 mg/m2 on days 1, 11 of hyper-CVAD and days 1, 8 of MTX-cytarabine courses for 8 total doses) regardless of age. CNS prophylaxis alternated intrathecal (IT) MTX day 2 with cytarabine day 7 for each of the 8 courses (total 16 ITs). An early report showed encouraging results in 31 non-HIV pts treated with hyper-CVAD and rituximab. 3-yr OS rates were similar (89% versus 88%) for the elderly and younger pts [Thomas, Cancer, 106:1569, 2006]. An additional 25 patients have been accrued since the previous report. Fifty-six pts with newly diagnosed non-HIV BL (n=28) or B-ALL (n=27) were treated. Median age was 45 years (range, 17–77); 25% were aged 60 yrs or older. Over 80% of cases were Ann Arbor stage III/IV. The overall CR rate in 44 evaluable pts (10 in CR at start due to one course of prior therapy or resected disease, 2 too early) was 95%; 2 pts achieved partial response. All pts aged 60 yrs or older achieved CR. The one induction death was observed in the younger group. After a median follow-up of 54 months (range, 1 – 124+ months), 3 relapses were observed. Nine pts died in CR related to infections (n=3), secondary malignancies (n=3), or other causes (n=3). In comparison with 48 historical BL or B-ALL pts treated with hyper-CVAD alone, the 5-yr rates for OS (75% vs 50%, p=.03), age < 60 yrs (74% vs 70%, p=NS), and age 60 yrs or older (73% vs 19%, p=.002) continued to favor hyper-CVAD with rituximab. Four pts developed secondary dyscrasias (1 with acute myelogenous leukemia [AML] at 7 yrs, 2 with myelodysplastic syndrome at 3–1/2 years, and 1 with t(8;21) AML at 3 yrs). Toxicity profile was otherwise similar to hyper-CVAD alone. Rituximab and hyper-CVAD appears to improve the disease-related outcomes for de novo Burkitt-type lymphoma/leukemia, particularly for the older patients. Long-term monitoring for secondary blood dyscrasias should be conducted across all age groups. Incorporation of the newer generation anti-CD20 monoclonal antibodies, such as ofatumumab, into hyper-CVAD merits investigation.

Disclosures:
Thomas: Novartis: Honoraria; Bristol-Meyer-Squibb: Honoraria; Pfizer:; Amgen: Research Funding. Off Label Use: Imatinib for de novo Philadelphia positive ALL. Dasatinib for de novo Philadelphia positive ALL. Rituximab for CD20 positive ALL and Burkitt leukemia/lymphoma. Nelarabine for de novo T-lymphoblastic leukemia/lymphoma. O'Brien:Genentech BioOncology: Consultancy. Wierda:Genentech BioOncology: Consultancy, Research Funding, Speakers Bureau. Ferrajoli:Genentech BioOncology: Research Funding.