On April 17, 2014, the FDA approved ofatumumab (Arzerra Injection; GlaxoSmithKline), in combination with chlorambucil, for the treatment of previously untreated patients with 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 versus chlorambucil alone. A total of 447 patients were included in the study and fludarabine-based therapy was deemed inappropriate for them because of advanced age or comorbidities. Overall, 72% of patients had ≥2 comorbidities, and 48% had a creatinine clearance of <70 mL/min.
The primary end point of the trial was 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 patients who received ofatumumab had ≥1 symptoms of infusion reaction. In addition, 10% of patients had a grade ≥3 infusion reaction.
The recommended regimen for ofatumumab in patients with previously untreated CLL is 300 mg on day 1, followed by 1000 mg on day 8 (cycle 1), followed by 1000 mg on day 1 of the subsequent 28-day cycles, for a minimum of 3 cycles and a maximum of 12 cycles.