FDA Approves Ofatumumab for Previously Untreated Chronic Lymphocytic Leukemia

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The U.S. Food and Drug Administration (FDA) has approved ofatumumab (Arzerra) injection in combination with chlorambucil (Leukeran) for the treatment of previously untreated patients with chronic lymphocytic leukemia (CLL), for whom fludarabine-based therapy is considered inappropriate.

The approval was based on the results of a multicenter, randomized, open-label trial comparing ofatumumab in combination with chlorambucil to single-agent chlorambucil. 

Trial Details

The trial enrolled 447 patients for whom fludarabine-based therapy was considered to be inappropriate by the investigator for reasons that included advanced age or presence of comorbidities.

In the overall trial population, the median age was 69 years (range, 35–92 years), 72% of patients had two or more comorbidities, and 48% of patients had a creatinine clearance < 70 mL/min. 

Patients received ofatumumab as an intravenous infusion according to the following schedule: 300 mg administered on cycle 1 on day 1, 1,000 mg administered on cycle 1 on day 8, and 1,000 mg administered on day 1 of all subsequent 28-day cycles. In both arms, chlorambucil was given at a dose of 10 mg/m2 orally on days 1 to 7 every 28 days. Prior to each infusion of ofatumumab, patients received acetaminophen, an antihistamine, and a glucocorticoid. The primary endpoint of the trial was progression free survival.


Median progression-free survival was 22.4 months (95% confidence interval [CI] = 19.0–25.2 months) for patients receiving ofatumumab in combination with chlorambucil vs 13.1 months (95% CI = 10.6–13.8 months) for patients receiving single-agent chlorambucil (hazard ratio = 0.57, 95% CI = 0.45–0.72, stratified log-rank P < .001). 

The most common adverse reactions (≥ 5%) with ofatumumab in combination with chlorambucil (≥ 2% more than in the control arm) were infusion reactions, neutropenia, asthenia, headache, leukopenia, herpes simplex, lower respiratory tract infection, arthralgia, and upper abdominal pain. Overall, 67% of patients who received ofatumumab experienced one or more symptoms of infusion reaction, and 10% of patients experienced a grade 3 or greater infusion reaction.

Regular Approval

The results of this randomized trial were adequate to fulfill the postmarketing requirement for GlaxoSmithKline to verify the clinical benefit of ofatumumab and, therefore, the approval of ofatumumab was converted from accelerated approval to regular approval.

The recommended dose and schedule for the approved regimen for ofatumumab in previously untreated CLL is 300 mg on day 1 followed 1 week later by 1,000 mg on day 8 (cycle 1) followed by 1,000 mg on day 1 of subsequent 28-day cycles for a minimum of 3 cycles until best response or a maximum of 12 cycles. ■