Objective: To evaluate the cost-effectiveness of obinutuzumab in combination with chlorambucil (GClb) versus rituximab plus chlorambucil (RClb) in the treatment of adults with previously untreated chronic lymphocytic leukemia (CLL) and with comorbidities that make them unsuitable for full-dose fludarabine-based therapy, from the perspective of the Spanish National Health System.
Methods: A Markov model was developed with three mutually exclusive health states: progression-free survival (with or without treatment), progression, and death. Survival time for the two treatments was modeled based on the results of CLL11 clinical trial and external sources. Each health state was associated with a utility value and direct medical costs. The utilities were obtained from a utility elicitation study conducted in the UK. Costs and general background mortality data were obtained from published Spanish sources. Deterministic and probabilistic analyses were conducted, with a time frame of 20 years. The health outcomes were measured as life years (LYs) gained and quality-adjusted life years (QALYs) gained. Efficiency was measured as the cost per LY or per QALY gained of the most effective regimen.
Results: In the deterministic base case analysis, each patient treated with GClb resulted in 0.717 LYs gained and 0.673 QALYs gained versus RClb. The cost per LY and per QALY gained with GClb versus RClb was €23,314 and €24,838, respectively. The results proved stable in most of the univariate and probabilistic sensitivity analyses, with a probabilistic cost per QALY gained of €24,734 (95% confidence interval: €21,860–28,367).
Conclusion: Using GClb to treat patients with previously untreated CLL for whom full-dose fludarabine-based therapy is unsuitable allows significant gains in terms of LYs and QALYs versus treatment with RClb. Treatment with GClb versus RClb can be regarded as efficient when considered the willingness to pay thresholds commonly used in Spain.

Keywords: chlorambucil, chronic lymphocytic leukemia, cost-effectiveness, obinutuzumab, rituximab 

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Chronic lymphocytic leukemia (CLL) is a chronic lymphoproliferative syndrome and is the most common hematological malignancy in Western countries.1 In Spain, the incidence is estimated at 4.2 and 3.1 cases per 100,000 inhabitants a year in males and females, respectively;2 hence, about 1,600 new cases are diagnosed each year. The mean age of CLL patients at diagnosis is ~70 years, and the disease is uncommon in individuals under 65 years of age.2,3 Patients with CLL show a mean survival of up to 10 years.4 The presentation at diagnosis, the genetic and molecular profile, and the clinical course of the disease are so heterogeneous that the approach to treatment depends on the characteristics of both the disease and the patient, particularly on the presence or absence of comorbidities.1 Due to the indolent nature of the disease, it is estimated that approximately one-third of patients with CLL will never require treatment, while the rest will be treated immediately or at an earlier period to 5 years after diagnosis.5

Immunochemotherapy with rituximab, fludarabine, and cyclophosphamide (FCR) is currently the standard therapy in previously young untreated patients in the absence of comorbidities.1 However, many patients with CLL cannot receive FCR due to the excessive toxicity of fludarabine and their physiological conditions.1,6 These patients often receive monotherapy with chlorambucil (Clb) in the presence of severe comorbidities, or a combination of rituximab with Clb (RClb) in the case of patients with moderate comorbidities.1 However, the results of these treatments remain unsatisfactory.1,7,8