CD20 expression has emerged as an adverse prognostic factor in patients with acute lymphoblastic leukemia (ALL), forming the rationale for incorporation of CD20-directed immunotherapy such as rituximab to standard dose-intensive chemotherapy regimens, which has resulted in improved clinical outcomes in patients with ALL.1 Ofatumumab (HuMax-CD20) is another CD20-directed monoclonal antibody that is being evaluated in combination with the intensive hyper-CVAD regimen in adult patients with newly diagnosed ALL. The results of this phase 2 trial were reported by Sasaki and colleagues at ASH 2015.2 In the study population of 43 eligible patients with de novo ALL, nearly half the patients had abnormal baseline cytogenetics, and the majority had CD20 expression above 20%. The majority (98%) of the patients achieved a complete response (CR) after induction therapy; and 42 (93%) patients achieved minimal residual disease negativity overall. Seventeen patients went on to receive maintenance therapy in CR; 4 patients received induction-consolidation treatment, and 6 patients underwent allogeneic stem-cell transplantation. The 3-year progression-free survival was 75%, and the 3-year overall survival rate was 67%. Median time to neutrophil recovery for cycle 1 was 18 days, and that for platelet recovery was 21 days following induction therapy. Grade 3/4 toxicity included elevated liver function tests (32%), elevated bilirubin (17%), nausea/vomiting (10%), mucositis (7%), neuropathy (7%), and thrombotic events (2%). Febrile neutropenia episodes during induction occurred in 67% of patients and during consolidation cycles in 89%. At a median follow-up of 15 months, 2 patients relapsed and 1 had molecular relapse only. Overall, 9 deaths were reported, including due to sepsis, intracranial bleed, and progressive disease. Based on these study results, the authors concluded that the combination of hyper-CVAD with ofatumumab is safe and highly effective in patients with CD20-positive ALL.
