Note: REQUIRES PRECERTIFICATION.*
Aetna considers obinutuzumab (Gazyva) medically necessary for use in combination with chlorambucil for previously untreated chronic lymphocytic leukemia (CLL) in individuals without active hepatitis B virus infection.
Aetna considers obinutuzumab experimental and investigational for all other indications.
Note: * Precertification of obinutuzumab (Gazyva) is required of all Aetna participating providers and members in applicable plan designs. For precertification of obinutuzumab, call (866) 503-0857, or fax (866) 267-3277.
Chronic lymphocytic leukemia (CLL) represents the most prevalent adult leukemia and the introduction of therapeutic antibodies has increased the number of available treatments. For both previously untreated symptomatic CLL and as salvage therapy, rituximab, a CD20 antibody, is currently widely used in combination-based strategies. Recent data suggest that the addition of rituximab to fludarabine with or without cyclophosphamide prolongs survival in younger patients with CLL. Other improved CD20 antibodies with promising clinical activity, include ofatumumab and obinutuzumab (GA-101). Alemtuzumab, a CD52 antibody, likewise has demonstrated benefit in both symptomatic, previously untreated CLL and in patients with relapsed disease. Also, recent efforts to combine currently applied therapeutic antibodies with other biologic and targeted therapies with efficacy in CLL offers the potential to move toward alternative non-chemotherapy-based treatment approaches (Jaglowski et al, 2010).
Laprevotte et al (2013) reported that rituximab combined with chemotherapy is a standard treatment for CLL. They investigated whether endogenous IL-8 affects rituximab or obinutuzumab (GA-101) B-leukemic depletion mediated by natural killers. Rituximab, and more significantly obinutuzmab, were effective in B-cell depletion and natural killer activation using whole peripheral blood lymphocytes from untreated CLL patients.
Obinutuzumab was approved on November 1, 2013 by the Food and Drug Administration (FDA) for use in combination with chlorambucil for previously untreated CLL (NCI, 2013). Obinutuzmab is a CD20-cytolytic antibody. The FDA labeling produced by Genentech (2013) lists a boxed warning stating that “hepatitis B Virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients receiving CD20-directed cytolytic antibodies, including GAZYVA. Screen all patients for HBV infection before treatment initiation. Monitor HBV positive patients during and after treatment with GAZYVA. Discontinue GAZYVA and concomitant medications in the event of HBV reactivation... Progressive Multifocal Leukoencephalopathy (PML) including fatal PML, can occur in patients receiving GAZYVA.”
Dosing and administration of obinutuzumab includes premedication with glucocorticoid, acetaminophen and anti-histamine. Obinutuzumab is to be diluted and administered as intravenous infusion and is not to be administered as an intravenous push or bolus. The recommended dose for 6 cycles (28 day cycles) is as follows: 100 mg on day 1 Cycle 1; 900 mg on day 2 Cycle 1; 1000 mg on day 8 and 15 of Cycle 1; and 1000 mg on day 1 of Cycles 2 through 6 (Genentech, 2013).
An FDA news release stated that "Gazyva’s approval for CLL is based on a study of 356 participants in a randomized open-label multicenter trial comparing Gazyva in combination with chlorambucil to chlorambucil alone in participants with previously untreated CLL...Participants receiving Gazyva in combination with chlorambucil demonstrated a significant improvement in progression free survival: an average of 23 months compared with 11.1 months with chlorambucil alone" (FDA, 2013).