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FDA approves Arzerra in combination with chlorambucil for CLL
The FDA today approved the use of intravenous ofatumumab in combination with chlorambucil for patients with previously untreated chronic lymphocytic leukemia.
The combination of ofatumumab (GlaxoSmithKline) and chlorambucil is intended for patients with CLL who are not eligible for fludarabine (Fludara, Genzyme)-based therapy due to their age or comorbidities.
The FDA based its approval in part on results of a multicenter trial that evaluated ofatumumab plus chlorambucil vs. chlorambucil alone in 447 patients. The median age of the patients was 69 years (range, 35-92). Most patients had at least two comorbidities (72%), and 48% of patients had a creatinine clearance ˂70 mL/min.
All patients received 10-mg/m2 doses of chlorambucil on days 1 through 7 of 28-day cycles. Patients randomly assigned ofatumumab received a 300-mg intravenous dose on day 1 and a 1,000-mg dose on day 8 of the first cycle, followed by 1,000 mg on the first day of remaining cycles. The FDA approval recommends following the same dose and schedule for a minimum of 3 cycles and a maximum of 12 cycles.
Researchers reported longer median PFS among patients assigned to ofatumumab plus chlorambucil (22.4 months vs. 13.1 months; HR=0.57; 95% CI, 0.45-0.72).
More patients in the combination arm experienced infusion reactions, neutropenia, asthenia, headache, leukopenia, herpes simplex, lower respiratory tract infection, arthralgia and upper abdominal pain. Most patients assigned ofatumumab experienced at least one symptom of infusion reaction (67%), 10% of which were grade 3 or worse.
Perspective
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The announcement made by the FDA reports expanding of the approved label indication for ofatumumab to include previously untreated patients with CLL. The data that support this expanded indication clearly demonstrated improved outcomes, including response rates and PFS, with combined ofatumumab and chlorambucil over chlorambucil monotherapy, for previously untreated patients with CLL for whom standard fludarabine, cyclophosphamide, rituximab (Rituxan, Genentech/Biogen Idec [FCR] could not be given.
This represents another active “standard” regimen for first-line treatment of patients who cannot receive fludarabine-based combinations. I am excited about these positive data and progress with ofatumumab, and look forward to future first-line nonchemotherapy trials incorporating ofatumumab with the exciting new small-molecule inhibitors approved and/or in development.