Impact of Oral Targeted Therapy on the Economic Burden of Chronic Lymphocytic Leukemia in Canada

Abstract

Background: Continuous oral targeted therapy (OTT) for chronic lymphocytic leukemia (CLL) represents an effective therapy but also a major economic burden on the healthcare system. This study aimed to estimate future direct costs, along with the prevalence, of CLL in the era of continuous OTT in Canada. Methods: The economic burden of OTT was modelled and compared to chemoimmunotherapy (CIT), for CLL treatment. The burden was assessed/projected from 2011 to 2025. For the OTT scenario, CIT was considered the standard of care before 2015, while OTT was considered standard of care for patients with either unmutated immunoglobulin heavy-chain variable (IGHV) or del(17p)/TP53 mutations starting in 2015 and, from 2020 onwards, for all first-line treatments except for patients with mutated IGHV. A Markov model was developed including four health states: watchful-waiting, first-line treatment, relapse and death. Costs of therapy, follow-up/monitoring and adverse events were included. Key clinical parameters were extracted from pivotal clinical trials. Results: As incidence rates and rate of survival are increasing, the prevalence of CLL in Canada is projected to increase 1.8-fold, from 8301 patients in 2011 to 14,654 by 2025. Correspondingly, the total annual costs of CLL management are predicted to increase 15.7-fold, from $60.8 million to $957.5 million during that same period. Conclusions: Although OTT enhances survival for patients with CLL, it is nonetheless associated with an important economic burden due to the projected vast increase in costs from 2011 to 2025. Changes in clinical strategies, such as implementation of a fixed OTT treatment duration, could help alleviate financial burden.

Keywords: Markov model; chronic lymphocytic leukemia; economic burden; oral targeted therapy.

Figure 1

Markov model structure for patients with CLL. The health-state transition model comprises four health states: watchful waiting, first-line treatment, relapse and death. The Markov model developed simulates the course of patients with CLL, who may enter the model from either the watchful waiting or first-line treatment health states. CLL, chronic lymphocytic leukemia.

Figure 2

Management strategies for patients with CLL. (A) Treatment pattern of OTT scenario, with evolving therapeutic options over time. (B) Treatment pattern of CIT scenario, which continues the use of CIT as the standard of care through time. For the base-case analysis, the most widely used therapy was selected when more than one therapy was considered available for patients in the same condition (shown in bold). B, bendamustine; BR, bendamustine and rituximab; CIT, chemoimmunotherapy; Clb, chlorambucil; Clb+R, chlorambucil and rituximab; CLL, chronic lymphocytic leukemia; del(17p), deletion at chromosome 17p targeting the TP53 gene; F, fludarabine; FCR, fludarabine, cyclophosphamide and rituximab; FR, fludarabine and rituximab; GClb, obinutuzumab and chlorambucil; IGHV, immunoglobulin heavy-chain variable; OTT, oral targeted therapy; R, rituximab.

Figure 2

Management strategies for patients with CLL. (A) Treatment pattern of OTT scenario, with evolving therapeutic options over time. (B) Treatment pattern of CIT scenario, which continues the use of CIT as the standard of care through time. For the base-case analysis, the most widely used therapy was selected when more than one therapy was considered available for patients in the same condition (shown in bold). B, bendamustine; BR, bendamustine and rituximab; CIT, chemoimmunotherapy; Clb, chlorambucil; Clb+R, chlorambucil and rituximab; CLL, chronic lymphocytic leukemia; del(17p), deletion at chromosome 17p targeting the TP53 gene; F, fludarabine; FCR, fludarabine, cyclophosphamide and rituximab; FR, fludarabine and rituximab; GClb, obinutuzumab and chlorambucil; IGHV, immunoglobulin heavy-chain variable; OTT, oral targeted therapy; R, rituximab.

Figure 3

Trends in disease and cost^a burden of CLL for the CIT and the OTT scenarios. (A) The annual prevalence of CLL (excluding patients in the watchful waiting health state) under the CIT and OTT scenarios. The use of OTT is projected to increase the number of patients living with CLL from 8301 in 2011 to 14,654 by 2025 (1.8-fold increase). (B) The total costs of CLL management per year for the CIT and OTT scenarios. The use of OTT is projected to increase the annual costs from $60.8 million in 2011 to $957.5 million in 2015 (15.7-fold increase), which is mainly driven by the increased number of patients with CLL, high drug costs and the increased duration of treatment. CIT, chemoimmunotherapy; CLL, chronic lymphocytic leukemia; OTT, oral targeted therapy. ^aAll costs are shown in 2019 Canadian dollars.

Figure 4

Sensitivity analysis of the total annual costs ^a of CLL for the CIT and the OTT scenarios. (A) Tornado diagram for the one-way sensitivity analysis of the total annual cost for the CIT scenario. (B) Tornado diagram for the one-way sensitivity analysis of the total annual cost for OTT scenario. CIT, chemoimmunotherapy; CLL, chronic lymphocytic leukemia; del(17p), deletion at chromosome 17p targeting the TP53 gene; FC, fludarabine, cyclophosphamide; FR, fludarabine and rituximab; IGHV, immunoglobulin heavy-chain variable; IV, intravenous; OTT, oral targeted therapy. ^a All costs are shown in 2019 Canadian dollars.

Figure 4

Sensitivity analysis of the total annual costs ^a of CLL for the CIT and the OTT scenarios. (A) Tornado diagram for the one-way sensitivity analysis of the total annual cost for the CIT scenario. (B) Tornado diagram for the one-way sensitivity analysis of the total annual cost for OTT scenario. CIT, chemoimmunotherapy; CLL, chronic lymphocytic leukemia; del(17p), deletion at chromosome 17p targeting the TP53 gene; FC, fludarabine, cyclophosphamide; FR, fludarabine and rituximab; IGHV, immunoglobulin heavy-chain variable; IV, intravenous; OTT, oral targeted therapy. ^a All costs are shown in 2019 Canadian dollars.