Phase II study of the hyper-CVAD regimen in combination with ofatumumab as frontline therapy for adults with CD-20 positive ALL

Background: The hyperCVAD regimen is an effective frontline program for de novo adult ALL. CD20 expression was identified as an adverse prognostic factor, associated with a higher incidence of relapse and lower 3-year OS rates. Addition of rituximab to the hyperCVAD program in patients with CD20+ ALL improved outcome with 3-year CRD and OS rates by 68% and 65%, respectively. Ofatumumab targets a membrane proximal small-loop epitope on the CD20 molecule and was found to be more potent than rituximab. Combination of the hyperCVAD regimen and ofatumumab may be associated with better responses and higher 3-year PFS and OS rates. Methods: Pts with newly diagnosed ALL and pts who received 1 prior course of chemotherapy received 8 courses of hyperCVAD alternating MTX-Ara-C; ofatumumab was given on courses 1 through 4. This treatment is to be followed by POMP maintenance therapy for approximately 30 months, interrupted by intensifications months 6, 7 and 18, 19 with MTX/Pegylated asparaginase and hyperCVAD-ofatumumab. CNS prophylaxis was administered. Results: 21 pts with de novo ALL and 2 pts in CR previously treated have received a median of 7 cycles; 7 pts did not receive the full 8 planned courses. 15 pts are receiving maintenance in CR. Median age is 50 years. All but 1 pt (95%) achieved CR after cycle 1; 1 pt died of septic shock at C1D21. 22/23 pts (95%) achieved MRD negativity as assessed by FCI; of whom 14 (64%) after induction. Grade ≥ 3 toxicity included increased LFT's in 7 pts (30%), increased bilirubin in 6 (26%), thrombotic events in 1 (4%) and neuropathy in 1 (4%). Febrile neutropenia episodes during induction and consolidation cycles were reported at rates of 71% and 77%, respectively. With a median follow-up of 12 months, 21 pts are alive; two patients developed sepsis and died at C1D21 and C3D17, respectively. 2 pts have undergone ASCT: due to the lack of MRD negativity achievement in one and a highly complex karyotype at diagnosis in the second; the first relapsed 7 months post ASCT. The 1-year PFS and OS rates were 91% and 91% respectively. Conclusions: The combination of hyperCVAD/ofatumumab is safe and highly effective in pts with CD20 + ALL.