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FDA OKs Arzerra (Ofatumumab) as First-Line Treatment With Chlorambucil in Patients With CLL

Combo therapy more effective at improving survival than chlorambucil alone

The FDA has approved a supplemental biologic license application (sBLA) for the use of Arzerra (ofatumumab, GlaxoSmithKline/Genmab), a CD20-directed cytolytic monoclonal antibody, in combination with chlorambucil for the first-line treatment of previously untreated patients with chronic lymphocytic leukemia (CLL) for whom fludarabine-based therapy is considered inappropriate.

The agency’s approval was based on results from a phase III study that demonstrated a statistically significant improvement in median progression-free survival (PFS) in patients who received the combination of ofatumumab and chlorambucil compared with patients who received chlorambucil alone.

In the pivotal phase III, randomized, open-label, parallel-arm COMPLEMENT 1 study, ofatumumab in combination with the oral chemotherapeutic agent chlorambucil was compared with chlorambucil alone in 447 patients with CLL who were previously untreated and for whom fludarabine-based therapy was considered inappropriate by study investigators. The patients’ median age was 69 years, and most (72%) had two or more comorbidities.

The study’s primary efficacy measure was PFS, as assessed by a blinded independent review committee using the International Workshop for Chronic Lymphocytic Leukemia (IWCLL) updated National Cancer Institute-sponsored Working Group (NCI-WG) guidelines (2008). Secondary efficacy endpoints included overall response, complete response, and duration of response.

The results from the COMPLEMENT 1 trial demonstrated a statistically significant improvement in median PFS in patients randomly assigned to receive ofatumumab and chlorambucil (n = 221) compared with those assigned to receive chlorambucil alone (n = 226) (22.4 months versus 13.1 months, respectively; hazard ratio, 0.57; P < 0.001).

The most common non–infusion-related ARs (all grades), as reported by investigators within 60 days after the last treatment, included neutropenia (27% of the ofatumumab + chlorambucil groups vs. 18% of the chlorambucil group), asthenia (8% vs. 5%), headache (7% vs. 3%), leukopenia (6% vs. 2%), herpes simplex (6% vs. 4%), lower respiratory tract infection (5% vs. 3%), arthralgia (5% vs. 3%), and upper abdominal pain (5% vs. 3%).

Infusion reactions (IRs) were seen in 67% of patients in the ofatumumab + chlorambucil arm. Ten per cent of these IRs were grade 3 or greater. IRs that were grade 3 or greater, were serious, or led to treatment interruption or discontinuation occurred most often with cycle 1 and decreased with subsequent infusions.

With the exception of neutropenia and leukopenia, the overall rate of non–infusion-related grade-3 or greater reactions with ofatumumab in combination with chlorambucil was similar to that of chlorambucil alone.

Source: GlaxoSmithKline; April 17, 2014.

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