Economic Analysis of Alemtuzumab in Fludarabine-Refractory and Relapsed Chronic Lymphocytic Leukemia in Canada

Background: Alemtuzumab (ALEM), a humanized antibody that recognizes the CD52 antigen, is indicated for the treatment of B-cell chronic lymphocytic leukemia (CLL) in patients who have been treated with alkylating agent and who had failed fludarabine therapy. The objective of this economic analysis was to determine the incremental cost-effectiveness of ALEM in patients with fludarabine-refractory and relapsed CLL from the perspective of a publicly funded health care system in Canada. ALEM was compared to accepted treatments for this patient population.

Methods: A two-year time horizon was used. Effectiveness and adverse event information was obtained from an extensive literature review process. Resource utilization was based on guidelines, literature and expert opinion. Costs were obtained from provincial sources and presented in 2008 Canadian dollars. Only direct medical costs were considered. A number of comparators were used to represent standard treatment: salvage therapy, which included a variety of literature-based treatment options for fludarabine-refractory patients, fludarabine+cyclophosphamide (FC), flud arabine+cyclophosphamide+rituximab (FCR), and best supportive care (BSC). BSC included the palliative costs for caring for individuals previously treated with FC.

Results: Mean survival for ALEM was 20.89 months (1.74 years), salvage therapy 16.32 months (1.36 years), FC 17.44 months (1.45 years), FCR 20.06 months (1.67 years). The incremental cost-effectiveness ratio (ICER) for the base case-ALEM vs. salvage therapy was Canadian $52,021/life year gained (LYG); ALEM vs. FC $68,165/LYG; ALEM vs. FCR $20,886/LYG. For ALEM vs. BSC, there was increased survival and cost savings with ALEM. Base case ICERs were sensitive to four variables: treatment duration of FC; treatment duration of FCR; treatment duration of ALEM; and additional survival due to rituximab for FCR patients compared to FC. Sensitivity analyses of the remaining variables showed minimal change to the base case ICERs. These variables were: ALEM administration (proportion of intravenous to subcutaneous); cytomegalovirus (CMV) complication rate for ALEM; discount rate; neutropenia and thrombocytopenia rates for ALEM; and neutropenia and thrombocytopenia rates for FCR.

Conclusion: The results show that ALEM has a favourable ICER and provided good economic value for patients with fludarabine-refractory and relapsed CLL when compared to salvage therapy, FC and FCR. ALEM was found to be dominant over BSC.