Purpose: To determine the cost-effectiveness of rituximab plus fludarabine and cyclophosphamide compared to fludarabine and cyclophosphamide alone in the management of previously treated CLL in Canada. Chronic lymphocytic leukemia (CLL) is incurable disease and is the most prevalent form leukemia in industrialized countries. The results of the phase III REACH trial, in which were enrolled 552 subjects with previously treated CLL, showed significantly higher progression free survival (PFS) among those randomized to receive rituximab plus fludarabine and cyclophosphamide compared to those receiving fludarabine and cyclophosphamide alone (30.6 months vs. 20.6 months, respectively, P=0.0002). Given evidence of clinical superiority, information on cost-effectiveness is required by payer to make informed decisions about reimbursing the medication for this indication.
Methods: A lifetime Markov model with a monthly-cycle length was developed with three health states: 1) PFS; 2) disease progression and 3) death. Head-to-head efficacy data (PFS and overall survival) were obtained from the REACH trial. Resource use was determined through the REACH trial and a supplemental resource use questionnaire completed by hematologists/oncologists experienced in treating CLL. Costs were determined, where possible, from the perspective of the Ontario Ministry of Health; supplemental data from the literature was used as necessary. Due to the paucity of representative utility values for the target population, the inputs were determined by the means of the utilities from a UK- and a Canadian-based study that closely reflected the specific population of interest. Outcomes were life years (LY) and quality adjusted life years (QALY) in both groups. Costs (2010 $CAD) and outcomes were discounted at 5% annually. Incremental cost-effectiveness ratios (ICERs) were reported with one-way and probabilistic sensitivity analyses.
Results: A mean gain of 0.598 LYs (4.933 vs. 4.335) and 0.505 QALYs (3.753 vs. 3.249) was resulted when rituximab plus fludarabine and cyclophosphamide compared to fludarabine and cyclophosphamide alone over the lifetime period. The addition of rituximab to fludarabine and cyclophosphamide yielded an ICER of approximately $53,114/QALY (95% CI: 32,650, 98,694). The deterministic sensitivity analyses suggested that results were most sensitive to shorter time horizons and largely robust to changes in assumptions about the data inputs.
Conclusion: The addition of rituximab to fludarabine and cyclophosphamide is likely to offer good value for money in the management of previously treated CLL in Canada.
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