Ofatumumab Approved as Maintenance Therapy for CLL

January 27, 2016

The FDA granted approval to ofatumumab for the treatment of patients with recurrent or progressive chronic lymphocytic leukemia who are in complete or partial remission after two or more lines of prior therapy.

The US Food and Drug Administration (FDA) granted approval to the CD20-targeting monoclonal antibody ofatumumab (Arzerra) for the treatment of patients with recurrent or progressive chronic lymphocytic leukemia (CLL) who are in complete or partial remission after two or more lines of prior therapy.

This approval was based on clinical trials results that showed that patients with CLL assigned maintenance therapy with ofatumumab had close to double the progression-free survival (PFS) compared with patients who did not undergo maintenance therapy.

Results of the phase III PROLONG study were published in the October 2015 issue of Lancet Oncology. The trial included 474 patients with CLL in complete or partial remission after second- or third-line therapies. Patients were randomly assigned to receive maintenance therapy with ofatumumab (n = 238) for 2 years or observation (n = 236). With a median follow-up of close to 20 months, patients assigned ofatumumab had a median PFS of 29.4 months compared with 15.2 months in patients assigned observation (hazard ratio [HR], 0.50 [95% CI, 0.38–0.66]; P < .0001).

The most common grade 3 adverse events seen in the study were neutropenia and infections.

Commenting on the results of the trial in Lancet Oncology, Adrian Wiestner, MD, PhD, of the National Heart, Lung, and Blood Institutes, questioned if the benefits of maintenance therapy with ofatumumab would justify the cost and if maintenance therapy provides more benefits than retreatment at progression.

“The latter was addressed in the RESORT trial, in which patients with follicular lymphoma were randomly assigned to either rituximab maintenance treatment or retreatment with rituximab at the time of progression. Interestingly, patients in both treatment groups achieved comparable disease control, with less rituximab given to patients in the retreatment group,” Wiestner wrote.

However, he concluded that the PROLONG study provided “important data about the clinical benefit of ofatumumab maintenance.”

The FDA has approved maintenance ofatumumab with a recommended dose and schedule for ofatumumab of 300 mg by intravenous infusion on day 1 followed by 1,000 mg on day 8, then 7 weeks later, and then every 8 weeks thereafter for up to a maximum of 2 years.

Ofatumumab was approved in October 2009 for the treatment of patients with CLL whose cancer was no longer being controlled by other forms of chemotherapy. In April 2014, the drug was granted approval in combination with chlorambucil to treat patients with treatment-naive CLL for whom fludarabine-based therapy would not be appropriate.