Ofatumumab Approved for Chronic Lymphocytic Leukemia
The US Food and Drug Administration approved ofatumumab (Arzerra Injection, GlaxoSmithKline) in combination with chlorambucil, for the treatment of previously untreated patients with chronic lymphocytic leukemia, 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 with chlorambucil alone. The 447 patients included in the study were deemed ineligible for fludarabine-based therapy because of advanced age or comorbidities. Overall, 72% of patients had ?2 comorbidities, and 48% had a creatinine clearance of <70 mL/min.
Infusion of intravenous ofatumumab was administered as 300 mg in cycle 1 on day 1, followed by 1000 mg on day 8 (first arm), or 1000 mg administered on day 1 of all subsequent 28-day cycles (second arm). In both arms, chlorambucil was administered at a dose of 10 mg/m2 orally on days 1 to 7 every 28 days. Before each infusion of ofatumumab, patients received premedication with acetaminophen, an antihistamine, and a glucocorticoid.
The primary end point of the trial was progression-free survival (PFS) as assessed by a blinded independent review committee. The median PFS was 22.4 months (95% confidence interval [CI], 19-25.2) in patients receiving ofatumumab plus chlorambucil compared with 13.1 months (95% CI, 10.6-13.8) in patients receiving chlorambucil alone (hazard ratio, 0.57; 95% CI, 0.45-0.72; P <.001).
The most common adverse reactions (?5%) reported with ofatumumab plus chlorambucil were infusion reactions, neutropenia, asthenia, headache, leukopenia, herpes simplex, lower respiratory tract infection, arthralgia, and upper abdominal pain. Overall, 67% of the patientswho received ofatumumab had ?1 symptoms of infusion reaction. In addition, 10% of patients had a grade ?3 infusion reaction. (April 17, 2014)