Economic Evaluation of Ibrutinib as First-Line Treatment of Unfit Patients with Chronic Lymphocytic Leukemia in the Netherlands and the Potential Role of Precision Medicine

Chronic lymphocytic leukemia (CLL) is the most common form of leukemia in adults in Western countries. The prognosis for younger patients with CLL can be relatively good but the life expectancy of older (>65 years) or unfit patients is significantly impaired. Less than 60% of these older patients are alive 5 years after the diagnosis. The current standard treatment in the Netherlands for this type of cancer is obinutuzumab combined with chlorambucil (GClb). However, about a quarter of the patients do not respond to this treatment. A new therapy with ibrutinib shows promising results compared to GClb but it comes at very high costs. Currently ibrutinib is not reimbursed in the Netherlands for these patients. This study evaluated the cost-effectiveness of ibrutinib compared to GClb in the treatment of unfit CLL patients in the Netherlands, from the societal perspective. It also studied the potential of a possible test that can predict which patients are expected not to respond to GClb and how it affects the cost-effectiveness of treating only these patients with ibrutinib. A partitioned survival model was developed with three mutually exclusive health states: progression-free survival (receiving or not receiving therapy), progression, and death. Curves for progression-free survival and overall survival were extrapolated based on the results of two randomized controlled trials. Utilities were derived from an elicitation study on CLL health states in the UK. Costs and background mortality were obtained from a variety of Dutch sources. Ibrutinib was estimated to lead to 1.79 more life-years (LYs) and 1.17 more quality-adjusted life years (QALYs) compared to GClb, at an additional cost of €432,224. This combined led to €240,913 costs per LY gained and €369,657 (95% C.I.: €190,169-1,160,357) per QALY gained. The effect of a possible stratification test that predicts the treatment response to GClb on the ICER was modeled. The percentage of patients with a complete response to GClb (22.3%) was combined with the median time of no progression for these patients (76 months). The stratification test leads to 1.12 more QALYs and €320,421 in additional costs compared to GClb. This combined leads to an ICER of €285,847 (C.I.: €149,051-434,968) per QALY gained compared to GClb. Ibrutinib for previously untreated and unfit CLL patients in the Netherlands is not a cost-effective strategy compared to the standard treatment of GClb when an €80,000 ICER threshold is used. A possible test predicting the individual response to GClb can lower the incremental costs while having a similar gain in QALYs. But even this strategy of using a stratification test is estimated not to be cost-effective compared to standard treatment.