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)