Ofatumumab, a human anti-CD20 monoclonal antibody, has been shown to be effective as monotherapy in patients with refractory CLL (Barth MJ, Czuczman MS. Future Oncol.2013;9:1829-1839). However, the effects of maintenance therapy on outcomes in CLL are currently unknown. To assess the effects of ofatumumab maintenance therapy, the PROLONG trial was initiated; this was an open-label, 2-armed randomized study of ofatumumab versus observation in patients with CLL who were in remission after induction treatment for relapsed CLL (van Oers MHJ, et al. Blood. 2014;124. Abstract 21).
A total of 474 patients who had achieved complete remission or partial remission after second-line or third-line treatment for CLL were randomized to receive ofatumumab maintenance or observation. Patients were stratified according to the number of previous reinduction regimens, whether they had achieved complete remission or partial remission at study entry, and whether they had received previous immunochemotherapy or only alkylator monotherapy. After a median follow-up of 19.1 months, a planned interim analysis was performed.
The median PFS (which was the primary clinical end point of the study) was 29.4 months in the ofatumumab group and 15.2 months in the observation group (hazard ratio, 0.50; P <.001). These significant differences between the 2 groups favoring ofatumumab were maintained regardless of the patients’ MRD status at study entry, high-risk cytogenetics (del17p or del11q), level of ?2-microglobulin, and IGVH mutation status. The time to the start of the next therapy was significantly longer in the ofatumumab group than in the observation group (38.3 vs 31.1 months), but as of this report, there were no significant differences between the 2 groups in OS. The incidence of grade 3/4 adverse events was higher in the ofatumumab group than in the observation group (25% vs 17%, respectively), especially with respect to infections, neutropenia, and pneumonia.
These data suggest that ofatumumab maintenance provides a significant clinical benefit for patients with relapsed CLL, with a safety profile that is characteristic of anti-CD20 therapy.
