Chemo-Immunotherapy with Hyper-CVAD Plus Ritixumab for Adult Burkitt’s and Burkitt’s Type Lymphoma (BL) or Acute Lymphoblastic Leukemia (B-ALL).

Prognosis has improved for BL/B-ALL, particularly with short, intensive, multi-agent chemotherapy. Outcome of 26 non-HIV BL/B-ALL patients (pts) treated with hyper-CVAD (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone) showed CR rate of 81% with induction mortality 19% owing to systemic fungal infections in pts aged 60 years (yrs) and older [Thomas et al, JCO 17:2461, 1999]. Older age was also an adverse feature predicting relapse with shorter 3 yr survival compared with younger pts (17% vs 77%). To evaluate the addition of rituximab, a CD20 monoclonal antibody, to hyper-CVAD, 31 adults with newly diagnosed HIV negative BL (n=15) or B-ALL (n=16) received hyper-CVAD with rituximab. Their median age was 46 years; 29% were 60 years or older. Course 1 was given in laminar air flow room for pts aged 60 years or older. Rituximab 375 mg/m² was given intravenously days 1 and 11 of hyper-CVAD courses and days 1 and 8 of methotrexate and cytarabine courses with 16 intrathecal treatments (methotrexate day 2 and cytarabine day 7 of each course). No maintenance chemotherapy was given. No allogeneic or autologous stem cell transplant was planned in first CR. Complete remission (CR) was achieved in 24 of 28 evaluable patients (86%); 3 had a partial response and 1 had resistant disease. There were no induction deaths. The 3-year overall survival (OS), event-free survival, and disease-free survival rates were 89%, 80% and 88% respectively. All nine elderly pts aged ≥ 60 yrs achieved CR with all but one in continuous CR (death in CR from infection); 3-year OS rate was 89%. Nineteen pts (61%) were older than 40 yrs; OS rate was 90% compared with 35% for historical group (48 pts treated with hyper-CVAD alone). Reduction in the relapse rate with rituximab was observed compared with hyper-CVAD alone (7% versus 34% overall, p=0.008; 0% versus 50% for elderly, p=0.02; 11% versus 29% for age < 60 years, p=0.11). Toxicity profile was similar to hyper-CVAD alone. Multivariate analysis of the current cohort and historical group identified age and treatment with rituximab as factors predicting cure. The addition of rituximab to hyper-CVAD appears to improve outcome in adult BL or B-ALL, particularly in elderly patients.