FDA Approves Ofatumumab Combination for Relapsed Chronic Lymphocytic Leukemia

The U.S. Food and Drug Administration (FDA) approved ofatumumab in combination with fludarabine and cyclophosphamide for patients with relapsed chronic lymphocytic leukemia (CLL).

The approval was based on the results of the open-label, phase III COMPLEMENT-2 study that found ofatumumab plus fludarabine and cyclophosphamide resulted in a longer median progression-free survival (PFS; the study’s primary endpoint) than fludarabine and cyclophosphamide alone.

A total of 365 patients were randomized to receive:

  • 300 mg of ofatumumab on day 1 of the first cycle followed by 1,000 mg on day 8, with subsequent cycles dosed at 1,000 mg on day 1 plus fludarabine and cyclophosphamide (triplet combination; n=183)
  • fludarabine and cyclophosphamide alone (control; n=182)

The overall response rate in the ofatumumab-treated group was 84 percent, compared with 68 percent in the fludarabine and cyclophosphamide group (p=0.0003). Complete response rates were 27 percent versus 7 percent, respectively.

The PFS in the ofatumumab-treated group was 28.9 months, compared with 18.8 months for patients treated with fludarabine and cyclophosphamide (hazard ratio [HR] = 0.67; 95% CI 0.51-0.88; p=0.0032). The duration of response was also longer in the triplet combination group (29.6 months vs. 24.9 months for the doublet; HR=0.77; 95% CI 0.56-1.05; p=0.0878).

Treatment-related adverse events (AEs) were similar in both study arms. Grade ≥3 AEs occurred in 74 percent of those treated with the triplet regimen compared with 69 percent in the control group. Fifty-three percent of patients who received triplet therapy experienced grade ≥3 neutropenia versus 39 percent of those in the control group. Infusion-related reactions occurred in 4 percent of those treated with the ofatumumab combination compared with <1 percent in the control group.

Source: Genmab press release, August 31, 2016.