A Prospective Economic Analysis of Early Outcome Data From the Alliance A041202/ CCTG CLC.2 Randomized Phase III Trial Of Bendamustine-Rituximab Compared With Ibrutinib-Based Regimens in Untreated Older Patients With Chronic Lymphocytic Leukemia

Abstract

Introduction: The Alliance A041202/CCTG CLC.2 trial demonstrated superior progression-free survival with ibrutinib-based therapy compared to chemoimmunotherapy with bendamustine-rituximab (BR) in previously untreated older patients with chronic lymphocytic leukemia. We completed a prospective trial-based economic analysis of Canadian patients to study the direct medical costs and quality-adjusted benefit associated with these therapies.

Methods: Mean survival was calculated using the restricted mean survival method from randomization to the study time-horizon of 24 months. Health state utilities were collected using the EuroQOL EQ-5D instrument with Canadian tariffs applied to calculate quality-adjusted life years (QALYs). Costs were applied to resource utilization data (expressed in 2019 US dollars). We examined costs and QALYs associated ibrutinib, ibrutinib with rituximab (IR), and BR therapy.

Results: A total of 55 patients were enrolled; two patients were excluded from the analysis. On-protocol costs (associated with protocol-specified resource use) were higher for patients receiving ibrutinib (mean $189,335; P < 0.0001) and IR (mean $219,908; P < 0.0001) compared to BR (mean $51,345), driven by higher acquisition costs for ibrutinib. Total mean costs (over 2-years) were $192,615 with ibrutinib, $223,761 with IR, and $55,413 with BR (P < 0.0001 for ibrutinib vs. BR and P < 0.0001 for IR vs. BR). QALYs were similar between the three treatment arms: 1.66 (0.16) for ibrutinib alone, 1.65 (0.24) for IR, and 1.66 (0.17) for BR; therefore, a formal cost-utility analysis was not conducted.

Conclusions: Direct medical costs are higher for patients receiving ibrutinib-based therapies compared to chemoimmunotherapy in frontline chronic lymphocytic leukemia, with the cost of ibrutinib representing a key driver.

Keywords: Chronic lymphocytic leukemia, Ibrutinib, Bendamustine-rituximab, Phase III trial; Economic analysis.

Figure 1.

Progression-free survival (PFS) and Overall Survival (OS) at 2-years for bendamustine-rituximab (BR), ibrutinib-rituximab (IR), and ibrutinib (I).

Figure 1.

Progression-free survival (PFS) and Overall Survival (OS) at 2-years for bendamustine-rituximab (BR), ibrutinib-rituximab (IR), and ibrutinib (I).

Figure 2.

Mean Utility Scores (EQ5D) By Treatment Arm

Figure 3.

Disaggregated Costs (A. On Protocol Costs and B. Off Protocol Costs). A. On Protocol Mean Costs (y-axis) By Treatment Arm (x-axis) B. Off Protocol Mean Costs (y-axis) By Treatment Arm (x-axis)

Figure 3.

Disaggregated Costs (A. On Protocol Costs and B. Off Protocol Costs). A. On Protocol Mean Costs (y-axis) By Treatment Arm (x-axis) B. Off Protocol Mean Costs (y-axis) By Treatment Arm (x-axis)