Risk-Adapted, Ofatumumab-Based Chemoimmunotherapy and Maintenance in Treatment-Naïve CLL: A Phase II Study

Introduction: Anti-CD20 monoclonal antibodies (mAb) are an essential component of CLL therapy. Addition of anti-CD20 mAb to induction chemotherapy improves progression-free survival (PFS) and overall survival (OS) in treatment-naïve CLL. Patients who achieve minimal residual disease negativity (MRD-) after induction chemoimmunotherapy (CIT) have prolonged PFS and OS. It is unclear, whether an extended therapy with an anti-CD20 mAb after induction CIT can improve the depth of response and long-term outcomes in patients with detectable residual disease (MRD+). Here we report results from a phase II study using risk-adapted, ofatumumab-based CIT induction followed by ofatumumab maintenance in treatment-naïve CLL patients. (NCT01145209) Methods: Treatment-naïve CLL patients were stratified twice: first, based on pre-treatment FISH, and second, based on post-induction peripheral blood (PB) MRD status. Patients with high-risk FISH (17p or 11q deletion) received up to 6 cycles of fludarabine, cyclophosphamide and ofatumumab (FCO). Patients without high-risk FISH received fludarabine, and ofatumumab (FO). Ofatumumab was dosed at 300mg for the first cycle, and 1000mg for subsequent cycles. After induction, patients were re-stratified based on PB MRD status using flow cytometry. MRD- was defined