Cost Effectiveness of First-Line Therapies for Treatment-Naïve Chronic Lymphocytic Leukaemia in South Africa

Chronic lymphocytic leukaemia (CLL) is a common adult leukaemia, and selecting the most effective first-line treatment is crucial for optimising patient outcomes and managing healthcare costs. While chemoimmunotherapy (CIT) has been the standard approach, targeted therapies offer promising alternatives for treatment-naïve CLL patients. The objective of this study was to evaluate the cost effectiveness of chemoimmunotherapy compared to targeted therapies for treatment-naïve CLL patients in South Africa. A cost-effectiveness analysis was conducted using a Markov model based on three health states: progression-free survival (PFS), progression, and death. The model employed a 15-year time horizon and a 1-month cycle length. Patient-level data were reconstructed, and parametric estimation was used to project long-term clinical outcomes. Cost estimates were derived from national tariffs, reflecting a South African public healthcare perspective, while utilities were sourced from published literature. Outcomes were measured in total costs and quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were calculated and compared to a willingness-to-pay (WTP) threshold, and sensitivity analyses were conducted to test the robustness of the results. Among the evaluated treatment strategies, chlorambucil-plus-obinutuzumab (ClbO) had the lowest cost and served as the reference comparator. Both CIT regimens were cost effective, with fludarabine, cyclophosphamide, and rituximab (FCR) yielding an ICER of US1645. 52 per QALY gained and bendamustine-plus-rituximab (BR) had an ICER of US1716. 79 per QALY gained, both below the US3407 WTP threshold, under the model assumptions. Ibrutinib generated the highest QALYs but at a higher cost, resulting in an ICER of US19, 679. 52 per QALY gained and a 0% probability of being cost effective at the WTP threshold, while venetoclax-plus-obinutuzumab (VenO) was extendedly dominated, and therefore eliminated from the results. Sensitivity analyses confirmed the robustness of the findings across variations in key parameters. In the South African public healthcare setting, CIT regimens (FCR and BR) represent cost-effective first-line treatment strategies for symptomatic, treatment-naïve CLL. Bendamustine-plus-rituximab emerged as the most decision-robust option under uncertainty, while FCR yielded the lowest point-estimate ICER. Among CIT regimens, FCR may be preferred in fit patients, while BR represents a more decision-robust option in older or unfit populations. Targeted therapies such as ibrutinib and VenO, despite superior clinical efficacy, are not cost effective at current prices. Substantial price reductions, generic entry, or targeted use in high-risk subgroups may improve their value and enable equitable access within South Africa’s resource-constrained health system.