Costs Associated with TKI Treatment Failure for Patients with CML

Tampa—Chronic myeloid leukemia (CML) is a rare blood and bone marrow disease that occurs in 1.6 per 100,000 Americans. Tyrosine kinase inhibitors (TKIs) are currently the standard of care for CML. Prior to mid-2012—when the study period took place—3 TKIs were available: imatinib for first-line therapy and dasatinib and nilotinib for first-line or second-line therapy.

According to the National Comprehensive Cancer Network guidelines, following second-line failure, investigational drugs or hematopoietic stem cell transplantation are recommended rather than a third TKI. However, TKI treatment failure, due to resistance or intolerance, is a significant challenge in the treatment of CML, according to real-world data.

A recent study examined the economic burden of TKI treatment failure and associated costs by line of therapy during a 1-year post-failure from a managed care perspective. Y.J. Chen and colleagues presented this data at the AMCP meeting during a poster session titled Increasing Burden of Tyrosine Kinase Inhibitor (TKI) Treatment Failure with Later Lines of Therapy in Chronic Myeloid Leukemia (CML): A Real World Database Analysis.

The retrospective, cohort study used the IMS PharMetrics Plus Health Plan Claims Database, a fully adjudicated pharmaceutical and medical administrative claims data, with >150 million unique health plan members. This serves as a nationally representation of the commercially-insured US population with regard to age and gender.

Patients in the database with evidence of ≥1 claim for a TKI of interest between July 1, 2008, and December 31, 2011, were evaluated for eligibility. The number of unique TKIs used during a study period of 120 days prior to the index date was used to define the index line of therapy. Treatment failure was defined as a switch to a nonindex TKI or discontinuation of an index TKI, which was defined as a gap in pharmacy claims ≥60 days. The study end points were unadjusted and adjusted healthcare resource utilization and costs during the year following TKI treatment failure by line of therapy.

Among the 2734 eligible episodes with initiation of a TKI of interest, failure probabilities were lower following first-line initiation compared to second-line initiation, increasing over time from index: 34.6% vs 43% at 1-year post-index; 49.7% vs 57.6% at 2-years post-index; 55.9% vs 66.7% at 3-years post index.

In the 120 days pre-index, second-line failure had significantly higher total costs (median, $21,102 vs $6919; P<.001). Episodes with second-line failure also progressed more rapidly to treatment failure following initiation (median, 90 vs 126 days post-index; P<.001). Third-line failure episodes progressed to treatment failure twice as quickly as second-line failure, with a median of 45 days post-index.

In terms of adjusted healthcare resource utilization and costs in the year post-treatment failure, second-line failure had 45% more ambulatory visits and 75% higher odds of hospitalizations compared with first-line failure. Second-line failure also had 38% higher total healthcare costs, 73% higher total medical costs, and 39% higher ambulatory visit costs compared with first-line failure.

The study’s authors noted limitations, including the claims data were collected for payment and not clinical research and cannot provide clinical detail and accuracy that may be obtained through patient chart review. Also, the study sample represents a combination of commercially-insured and Medicare/Medicaid beneficiaries in a managed care setting, and the data may not be applicable to insured patients in nonmanaged care settings or in the uninsured/underinsured populations.

Overall TKI treatment failure is costly, with 1-year economic burden after TKI treatment failure increasing with each line of therapy: $78,667 for first-line failure, $99,624 for second-line failure, and $181,029 for third-line failure. The study’s authors noted that using more efficacious treatment in an earlier line of therapy to minimize treatment failure may help reduce downstream costs.—Kerri Fitzgerald

This study was sponsored by ARIAD Pharmaceuticals, Inc.