Impact of Care Cost on TKI Adherence in Patients With CML

By Gary H. Lyman, MD, MPH(Biostatistics), FASCO, FACP, FRCP, Professor, Public Health Sciences and Clinical Research Divisions, Fred Hutchinson Cancer Research Center

My name is Gary Lyman. I am a Hematologist and Medical Oncologist with a background in biostatistics and health outcomes research. I currently am Professor in the Divisions of Public Health Sciences and Clinical Research at the Fred Hutchinson Cancer Research Center where I serve as Senior Lead, Healthcare Quality and Policy in the Hutchinson Institute for Cancer Outcomes Research. I am also Professor in the University of Washington Schools of Medicine, Public Health and Pharmacy in Seattle.

Nearly 10,000 individuals are diagnosed with chronic myelogenous leukemia (CML) annually in the United States. Until a couple of decades ago, a diagnosis of CML was almost synonymous with a death sentence with the only potentially curative treatment that of an allogeneic marrow transplant.

The introduction of the tyrosine kinase inhibitor (TKI) imatinib in 2001 revolutionized the treatment of CML with the possibility of living a normal life expectancy. As a result, there are nearly 200,000 individuals in the United States currently living with CML. However, the original cost of imatinib treatment (~$40,000/yr) has increased some 10-20%/year to approximately $140,000/yr.

When generic imatinib became available in 2016 it was priced nearly the same as the brand name imatinib in the US although only about one-tenth of that in Canada and much of the world. Several next generation TKIs for CML have subsequently been approved although no difference in survival compared to imatinib has been demonstrated and the price of these agents is even greater than that of imatinib. This is clearly contributing the rapidly escalating cost of cancer care in the US, far outpacing that in other countries with Medicare prohibited from negotiating drug prices despite requiring coverage.

All of this has resulted in enormous financial and emotional hardship often resulting in bankruptcy, loss of home, treatment noncompliance or stopping all together leading to devastating outcomes impacting most severally on minorities and the poorly insured.

In collaboration with Drs Eric Chow, Jennifer Wilkes, Lena Winestone, and others at the University of Washington and the Fred Hutchinson Cancer Research Center along with Dr Henry Henk at Optum Laboratories, we undertook a retrospective cohort study of patients treated between 2000 and 2016 (J Clin Pathways. 2020;6[6]:35-42). The study was funded by a grant from Stand Up 2 Cancer administered by the American Association of Cancer Research.

The initial results of this >2-year study demonstrated that the costs associated with treatment of patients with CML was significantly greater than that of other hematologic malignancies driven primarily by the costs of TKIs which continued to increase over that time period (JCO Oncol Pract. 2020 Aug 21. Epub ahead of print). At the same time, the proportion of patients eventually receiving imatinib declined with the next generation TKIs have become the most commonly prescribed agents.

In the most recent study, we extended the observations to the end of 2019 (ASH 2019; JAMA Oncol. 2020 Oct 1. Epub ahead of print). Out latest results confirm the increasing use of the newer TKIs with their cost representing the largest driver of healthcare expenditures in patients with CML. The use of the originator imatinib has essentially disappeared while the generic version has only partially offset the dominant use of next generation TKIs.   

For several years after approval of generic imatinib, the price remained nearly as high as the brand name imatinib and the newer TKIs. There are now 11 approved generic forms of imatinib and in the most recent results the price of imatinib has fallen quite dramatically. Nevertheless, despite data suggesting that there is no difference in the survival of patients with CML treated with the newer TKIs compared to imatinib, the former have become the dominant agents used for treatment of CML accompanied by devastatingly high costs.

The average daily cost of TKIs for CML now exceed $350 driven almost entirely by the high price of these agents. We conclude that even the fall in the generic price of imatinib will be insufficient to reduce the cost of cancer care in this population.

We believe, these incredibly high prices have potentially devastating consequences for patients with CML including delays in treatment, poor compliance, early cessation or even refusal to accept very effective and life-saving therapy leading to poorer outcomes for individuals with a potentially curable malignancy. The US desperately needs policies that address the rising price of all drugs including those for treatable cancers like CML as well as overall healthcare expenditures. Such policies must be of the highest priority for clinicians, payers, patient advocates and policy makers moving forward to address the devastating financial challenges for cancer patients and their families.

Further studies are underway and will soon be published related to the adverse events associated with the TKIs in patients with CML with significant differences between imatinib and the next generation TKIs. We do hope in future grants to continue to track the utilization and drivers of these extremely effective but costly drugs for patients with CML including their impact over the lifespan of patients, often measured in decades.

Much of our focus has turned to the rapidly expanding number of biologic therapies used for cancer treatment often associated with even more prohibitive prices given their novelty and complexity of development and production. Such therapies are often extremely effective or even curative and are now becoming a mainstay of treatment for many of the most common solid tumors and lymphomas. Unlike imatinib that can be replicated precisely and quite simply as a generic, biologic agents such as monoclonal antibodies are large, complex molecules produced in living systems that cannot be exactly reproduced.

However, as the patents on these molecules expire, many companies are hoping to grab a part of this very profitable marked by produce ‘highly similar’ biologics or biosimilars which replicate closely the structural and functional properties of the original biologic with no meaningful differences in safety or potency. While the goal is to compete with the expensive originator, the cost of research, development and production of these complicated agents is still exceptionally high limiting how much price reduction may result. While the experience in Europe and elsewhere is promising in terms of safety and some reduction in prices, the biosimilars are only now arriving in the clinic in the US and it is far too early to fully understand how rapidly and fully they will be adopted and used in practice as well as what impact on price competition and drug access they will provide.

While cancer drugs represent an important slice of the overall cost of healthcare, there are many additional drivers contributing to the unsustainable rise in such costs. These include the cost of testing such as scans and other advanced imaging procedures, as well as the incredibly high and rising cost of hospitalization in the United States. There is so much more work to be done both on the research side and in moving our political leadership and policy makers toward a more rational and affordable healthcare system. All of this must be driven by the goal of reducing the cost and availability of healthcare, improving the quality of cancer care and improving clinical outcomes, and eliminating the enormous economic and social disparities that continue to impact daily on the quality and quantity of life provided for our patients including those in greatest need.