An economic evaluation in PharmacoEconomics – Open determined that the fixed-duration combination of venetoclax (Venclexta) plus obinutuzumab (Gazyva; VEN+O) is a cost-effective treatment option for previously untreated, fit patients with chronic lymphocytic leukemia (CLL) in Canada.1
The determination was made based on the potential health benefits and cost savings associated with VEN+O against most comparator treatments, including BTK inhibitors, venetoclax plus ibrutinib (Imbruvica; VEN+I), and chemoimmunotherapies.
Data Sources and Methodology
This study was a cost-utility analysis examining the incremental costs of VEN+O and various treatments in Canadian dollars relative to “utility-based units,” or the health outcomes and benefits each treatment provides that relate to a person’s level of wellbeing.2 Outcomes measured included life years; quality-adjusted life years (QALYs), a measure of life years weighted to reflect quality of life within a particular year; and the incremental cost-utility ratio (ICUR), a ratio of the total cost difference between 2 treatments by the difference in outcomes between the 2 treatments, summarizing the additional cost per unit of health benefit gained as a result of the treatment over the comparator.3
The study utilized data from the CLL13 trial (GAIA; NCT02950051), a phase 3 trial that evaluated the efficacy of fixed-duration VEN+O against standard chemoimmunotherapies. Comparator treatments included fludarabine, cyclophosphamide, plus rituximab (Rituxan; FCR) for patients aged 65 years and younger, and bendamustine plus rituximab (BR) for patients over 65 years of age.4 The trial assessed these regimens in treatment-naive patients with CLL without del17p and TP53 mutations, with VEN+O treatment yielding superior progression-free survival (PFS) outcomes to both FCR and BR treatment.
For other treatments not evaluated in the CLL13 trial, data were obtained from a systematic literature review of clinical trials. Additional treatments examined included fixed-duration VEN+I, as well as the treat-to-progression regimens of ibrutinib, acalabrutinib (Calquence), and zanubrutinib (Brukinsa).
To conduct analyses, investigators developed and validated a 3-state partitioned survival model using extrapolated survival curves to estimate health state distributions of patients. The model included 3 health states: PFS, progressed disease, and death. In accordance with the dosing schedules for VEN+O and the comparator regimens, the model used a cycle length of 28 days. Sensitivity and scenario analyses were also conducted to confirm the robustness of the findings.
The model required several cost and utility inputs for analyses. Costs included drug acquisition and administration, monitoring, adverse events, subsequent treatment, and terminal care, which were derived from sources such as Canada’s Drug Agency (CDA-AMC) and the Canadian Institute for Health Information. As the CLL13 trial lacked data on relevant quality of life measures, utility inputs originated from the National Institute for Health and Care Excellence technology appraisals in CLL.
Key Findings: VEN+O Dominates Most Treatment Options
In terms of costs, the total cost per patient incurred over a 40-year lifetime horizon for VEN+O was $278,123 (95% CI, $198,925–$358,121), the second lowest after BR ($175,130; 95% CI, $39,114–$325,406). Of note, all treat-to-progression regimens were associated with higher costs compared with fixed-duration treatments such as VEN+O, which were noted to be largely driven by drug acquisition costs.
VEN+O also accrued a meaningful gain of life years and QALYs, reflective of its positive impact on patients’ quality of life. Specifically, VEN+O was second to VEN+I in total life years (18.62 for VEN+O; 18.82 for VEN+I) and ranked third in total QALYs (11.93; 95% CI, 7.99–14.84), trailing closely behind VEN+I (12.74; 95% CI, 7.94–16.02) and acalabrutinib (12.16; 95% CI, 7.20–15.72).
Placing costs and utilities into perspective, VEN+O was associated with lower total costs and higher QALYs compared with comparator treatments such as ibrutinib, zanubrutinib, and FCR. VEN+O also showed overall cost-effectiveness compared with acalabrutinib and VEN+I when considering the respective ICURs.
Collectively, these figures position VEN+O as the “dominant” option over most comparator treatments, simultaneously excelling in both cost-saving and overall health improvements.
“VEN+O was associated with favorable outcomes [vs] all comparators,” wrote authors van de Wetering et al in the study.1 “It could be assumed that VEN+O would likely also dominate [acalabrutinib] considering a similar efficacy between BTK [inhibitors]…but this could not be shown in this analysis due to the uncertainty of the [network meta-analysis] results.”
Perspectives From a Public Payer System
The pair of venetoclax, a targeted therapy, and obinutuzumab, an anti-CD20 antibody, has demonstrated therapeutic promise in several CLL trials including the
The results of this analysis illustrate the pharmacoeconomic viability of the 12-month fixed-duration VEN+O regimen for previously untreated, fit patients with CLL in the context of Canada’s public healthcare payer system. Notably, the CLL14 trial included patients who had coexisting medical conditions, a population prioritized for public reimbursement. Despite a later recommendation from the CDA-AMC for reimbursement of VEN+O for previously untreated fit patients with CLL, the combination is not publicly reimbursed across all Canadian provinces,1 underscoring potential geographic disparities in access to this cost-effective therapy.
As such, these findings may serve to guide funding allocation and future health policy decisions for equitable access to cost-effective CLL therapies.