A COST-EFFECTIVENESS EVALUATION OF IBRUTINIB FOR PATIENTS WITH RELAPSED CHRONIC LYMPHOCYTIC LEUKEMIA (CLL) IN BRITISH COLUMBIA, CANADA

Purpose:

   Ongoing discoveries into the biology of chronic lymphocytic leukemia (CLL) have uncovered genomic alterations that are associated with poor survival outcomes. The drug ibrutinib (Imbruvica^®; Janssen) offers an effective alternative to standard chemo-immunotherapy for patients with partial deletion of chromosome 17 (17p del); however, its relative cost-effectiveness for relapsed disease in British Columbia (BC) is unknown.

Method:

   A Markov model was designed to evaluate the cost-effectiveness of offering single-agent ibrutinib compared to standard care in 2 scenarios: scenario-1, relapsed patients with 17p del only, and scenario 2, all relapsed patients.

   We simulated a patient cohort transitioning between progression-free and relapsed disease health states, with an absorbing state of death. Time-dependent transitions and costs of care were calculated from a retrospective cohort of patients previously treated in BC. Transitions for ibrutinib-guided therapy were derived from published clinical trials, with costs taken from the literature. Incremental costs and life-years gained (LYG) accrued by patients over 5- and 15-year time horizons were calculated to determine the incremental cost-effectiveness ratio (ICER). Probabilistic sensitivity analysis was conducted on all model parameters. 

Result:

   Offering ibrutinib to 17p del patients (scenario-1) over a 5-year horizon was associated with higher mean costs ($133,490 vs. $55,333) and LYG (2.69 vs. 2.28) compared to standard care, at an ICER of $190,805/LYG (95% CI: $141,689-291,084). Over a 15-year time horizon, the ICER was $122,038/LYG (95% CI: $89,851-178,551).

   Offering ibrutinib to all relapsed patients (scenario-2) over a 5-year time horizon resulted in increased mean costs ($297,377 vs. $54,750) and LYG (3.59 vs. 2.37) compared to standard care, at an ICER of $199,663/LYG (95% CI: $166,533-246,968). Over a 15-year time horizon, the ICER was $126,089/LYG (95% CI: $110,751-146,340).

   The probability that either strategy is cost-effective at a given willingness-to-pay (WTP) threshold of $100,000 over a 15-year horizon is 10% for scenario-1, and <1% for scenario-2 (Fig.1).

Conclusion:

   Treatment of relapsed CLL patients in BC with ibrutinib may be cost-effective over a 15-year time horizon as gains in survival are realized. However, the cost-effectiveness of ibrutinib in a relapsed care setting can be improved. An area of current exploration is the impact on cost-effectiveness of using targeted gene sequencing to identify patients with resistance to, or need for, ibrutinib at the point of relapse.