The Food and Drug Administration has approved ofatumumab (Arzerra injection, for intravenous infusion) in combination with chlorambucil, for previously untreated patients with chronic lymphocytic leukemia for whom fludarabine-based therapy is considered inappropriate.
Ofatumumab, an anti-CD20-directed monoclonal antibody, manufactured by GlaxoSmithKline, was originally given an accelerated approval in 2009. As a condition of that approval, the company was required to conduct further studies. The trial used as the basis of the April 17 approval fulfilled that postmarketing requirement, and accelerated approval was converted to regular approval, said the FDA.
That multicenter, randomized, open-label trial compared ofatumumab in combination with chlorambucil to chlorambucil alone. Patients received an intravenous infusion of ofatumumab on the following schedule: 300 mg on cycle 1, day 1; 1,000 mg on cycle 1, day 8; and 1,000 mg on day 1 of all subsequent 28-day cycles. In both arms, chlorambucil was given at a dose of 10 mg/meter orally on days 1 to 7, every 28 days. Ofatumumab patients were premedicated with acetaminophen, an antihistamine, and a glucocorticoid.
Median progression-free survival was 22.4 months for patients receiving the combination, compared with 13.1 months for those who were given chlorambucil alone. Progression-free survival was assessed by a blinded independent review committee using the 2008 International Workshop on Chronic Lymphocytic Leukemia update of the National Cancer Institute Working Group guidelines.
The most common adverse reactions of the ofatumumab-chlorambucil combination were infusion reactions, neutropenia, asthenia, headache, leukopenia, herpes simplex, lower respiratory tract infection, arthralgia, and upper abdominal pain. Sixty-seven percent of patients who received ofatumumab experienced one or more symptoms of infusion reaction; 10% experienced a grade 3 or greater infusion reaction.
In September, the FDA added a black box warning to ofatumumab’s label on the risk of reactivation of hepatitis B virus infection in patients with prior infection.
For previously untreated chronic lymphocytic leukemia, the recommended dose and schedule is 300 mg on day 1; followed 1 week later by 1,000 mg on day 8; 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, according to the FDA.
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