FDA Updates Gazyva Label for Frontline Chronic Lymphocytic Leukemia

The Food and Drug Administration (FDA) has updated the label for Gazyva (obinutuzumab) plus chlorambucil to include data from stage 2 of the phase 3 CLL11 study, which detailed an unprecedented improvement in progression-free survival (PFS) compared with Rituxan (rituximab) plus chlorambucil as a frontline treatment for patients with chronic lymphocytic leukemia (CLL).

The combination of Gazyva plus chlorambucil was initially approved as a frontline therapy for patients with CLL in November 2013, based on data from stage 1 of the CLL11 trial. In this portion of the study, Gazyva plus chlorambucil reduced the risk of progression by 81 percent compared with chlorambucil alone (27.2 versus 11.2 months). In stage 2 of the study, Gazyva plus chlorambucil led to a median PFS of 26.7 months compared with 14.9 months with Rituxan and chlorambucil.

"Gazyva is the first and only medicine to significantly help people live without their disease worsening when combined with chlorambucil compared to Rituxan and chlorambucil in people with previously untreated chronic lymphocytic leukemia,” Sandra Horning, Genentech's chief medical officer and head of Global Product Development, said in a statement. “These new data enhance our understanding of the disease and its treatment, and this approval affirms an important treatment option for people with this difficult-to-treat disease.”

The phase 3 CLL11 trial enrolled patients who had not received prior treatments for CLL. The median age of patients was 73 years. In the three-arm study, 781 patients received six cycles every 28 days of chlorambucil, chlorambucil plus Gazyva, or chlorambucil plus Rituxan.

In stage 2 of the study, the overall response rate in the Gazyva arm was 79.6 percent compared with 66.3 percent with Rituxan. The complete response (CR) rate with Gazyva was 26.1 percent compared with 8.8 percent with Rituxan. The median duration of response with Gazyva was 19.6 versus 9.7 months with Rituxan.

Minimal residual disease (MRD) negativity in the bone marrow for patients who achieved a CR with or without complete recovery from abnormal blood cell counts was 19 percent with Gazyva versus 6 percent with Rituxan. In peripheral blood, 41 percent of patients treated with Gazyva were MRD negative compared with 12 percent with Rituxan.

The most common serious adverse events with Gazyva versus Rituxan were neutropenia, lymphopenia, leukopenia and thrombocytopenia. Infusion reactions occurred in 65 percent of patients treated with Gazyvain the phase 3study. Serious infusion reactions were seen in 20 percent of patients, with 7 percent discontinuing therapy.

Altogether, 47 of the first 53 patients enrolled in the study experienced an infusion reaction, warranting an early adjustment to study protocol to require premedication with a corticosteroid, antihistamine and acetamin along with dose adjustments. The FDA recommended dose for Gazyva is 100 mg on day 1 followed by 900 mg on day 2 and 1000 mg on day 8 and 15, for the first 28-day cycle followed by 1000 mg on day 1 of each subsequent cycle.