Prevalence and Economic Burden of Chronic Lymphocytic Leukemia (CLL) in the Era of Oral Targeted Therapies
Authors: Jain Nitin , Chen Qiushi , Ayer Turgay , O'Brien Susan M. , Keating Michael , Wierda William , Kantarjian Hagop M. , Jagpreet Chhatwal 
Published: October 2019

Abstract
Background: Better understanding of the disease biology has led to significant advances in the treatment of CLL. Oral targeted agents such as ibrutinib and idelalisib are currently approved for patients with relapsed CLL. Ibrutinib is also approved for first-line treatment of patients with del(17p). In addition, several other targeted therapies are expected to become available in the near future. These therapies (ibrutinib, idelalisib) have shown to improve survival in Phase III studies. However, their high cost, approaching more than $130,000/year for an indefinite duration of treatment, has raised concerns about their affordability and cost to the society (Shanafelt et al. JOP 2015). Our objective was to project the future prevalence and cost burden of CLL in the context of emerging therapeutic options.
Methods: We developed a Markov micro-simulation model representing the CLL population to project the prevalence and total cost of CLL in the United States for each year from 2011 to 2035. Our model was calibrated to the Surveillance, Epidemiology, and End Results (SEER) data and closely predicted the CLL prevalence in 2011. The model included new incidences every year, and considered the individual patient's aging, disease progression, and treatment with the available therapies in the given year. The disease progression was estimated from 10 published clinical trials presenting progression-free and overall survival data in first-line or relapse settings. For each patient, treatment was assigned based on the fitness status (determined by age) and the presence of del(17p). Cost estimation included the cost of drug, treatment administration, and management of adverse events. We simulated changes in the prevalence and the cost of CLL assuming oral targeted therapies as the standard-of-care for patients with relapsed CLL and for patients with del(17p) from 2014 onwards, and in the first-line setting from 2017 onwards (Fig 1A). For comparison, we also ran a scenario assuming chemoimmunotherapy (CIT) remains the standard-of-care from 2011 onwards (Fig 1B).
Results: With the emergence of oral targeted therapies, the prevalence of CLL is projected to increase from 120,000 in 2011 to 180,000 in 2025 (Fig 2A). Oral targeted therapies would result in additional 170,000 person-years in the next 10 years in the US. The annual cost of CLL treatment would increase from $0.9 billion in 2011 to $3.5 billion in 2025 (Fig 2B). Compared with CIT, oral targeted therapies would cost additional $15 billion over the course of next 10 years. The increase in prevalence and costs would be driven by substantially improved survival and continuous administration of the expensive oral therapies.
Conclusion: The new oral targeted agents represent a significant advance for the treatment of CLL and will substantially increase survival rates. However, they will dramatically increase the cost burden of CLL in the US. Such an economic impact could result in limited access and lower adherence to the oral therapies, which may undermine their clinical effectiveness. Given the increasing number of patients on first-line oral therapy that is continuously administered over an extended duration, a more sustainable pricing for such therapies is needed.
Figure 1. Scenarios of treatment strategies with emerging therapeutic options. Figure 1. Scenarios of treatment strategies with emerging therapeutic options. Figure 2. Estimates of prevalence and cost burden for oral targeted therapy and chemoimmunotherapy scenarios. Figure 2. Estimates of prevalence and cost burden for oral targeted therapy and chemoimmunotherapy scenarios.

Disclosures
Keating: Celgene Corp.: Consultancy; Glaxo-Smith-Kline Inc.: Other: Advisory board.