Ofatumumab Approved for Relapsed CLL

Genmab recently announced that the US Food and Drug Administration (FDA) has approved ofatumumab (Arzerra®) combined with fludarabine and cyclophosphamide (FC) for patients with relapsed chronic lymphocytic leukemia (CLL).

CLL is a type of cancer in which the bone marrow makes too many lymphocytes and tends to affect people of middle age, but rarely children, according to the National Cancer Institute (NCI). To date, treatment has involved using a chemotherapy sometimes paired with a monoclonal antibody or cytotoxic agent and sometimes the addition of a steroid.

Ofatumumab is a human monoclonal antibody designed to target the CD20 molecule found on the surface of CLL cells and normal B lymphocytes. It has been approved for patients in the United States for whom the first two lines for therapy have failed. Ofatumumab is also widely indicated internationally as a monotherapy for patients with CLL who experience refractory disease after prior treatment with fludarabine and alemtuzumab (Campath).

The FDA approval is based on results from the phase III COMPLEMENT 2 study that evaluated ofatumumab in combination with FC versus FC alone in patients with relapsed CLL. This open-label, two-arm, randomized, phase III study included 365 patients with relapsed CLL. Patients were randomly selected 1:1 to treatment with up to 6 cycles of ofatumumab in combination with fludarabine and cyclophosphamide (FC) or up to six cycles with fludarabine and cyclophosphamide alone.

The study met the primary endpoint with a median progression- free survival in patients receiving ofatumumab in combination with FC of 28.9 months, compared with 18.8 months in patients receiving FC alone (hazard ratio, 0.67; P = .0032). Secondary endpoints included overall response rate, overall survival, patient reported outcomes, time to response, duration of response, time to progression, time to next therapy, safety assessments, and quality of life. The safety profile observed in this study was consistent with other trials of ofatumumab and no new safety signals were observed.

This study is significant because CLL is commonly a disease that recurs after initial treatment and new studies are needed to determine a better regimen to slow down progression.