Disease-related mortality exceeds treatment-related mortality in patients with chronic myeloid leukemia on second-line or later therapy.

Treatment of newly-diagnosed patients with chronic-phase chronic myeloid leukemia (CP-CML) with tyrosine kinase inhibitors (TKIs) results in near-normal life expectancy. However, CP-CML patients resistant to initial TKIs face a poorer prognosis and significantly higher CML-related mortality. We conducted a systematic literature review to evaluate the specific causes of deaths (diseases progression versus drug-related) in CP-CML patients receiving second- or third-line therapy. We identified eight studies based on our criteria that reported causes of death. Overall, 5% of second-line and 10% of third-line patients died during the study follow-up period. For second-line, (7 studies, n=1926), mortality was attributed to disease progression for 41% of deaths, 2% to treatment-related causes, 3% were treatment-unrelated, and 50% were unspecified adverse events (AEs), not likely related to study drug. In third-line, (2 studies, n=144), 71% deaths were attributed to disease progression, 7% treatment-related AEs, 14% treatment-unrelated and 7% unspecified AEs. Annual death rates for second- and third-line therapy were significantly higher than for general population in similar age group. Our findings suggest death attributed to disease progression is approximately 10 times that due to treatment-related AEs in patients with CP-CML receiving second- or third-line therapy. Therefore, the potential benefits of effective treatment for these patients with the currently available TKIs outweigh the risks of treatment-induced AEs.

Increasing economic burden of tyrosine kinase inhibitor treatment failure by line of therapy in chronic myeloid leukemia.

OBJECTIVE: To assess the economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML), by assessing all-cause health care resource use (HCRU) and costs in the year after treatment failure by line of therapy (LOT; 1L/2L/3L) using real-world data. METHODS: Treatment episodes initiating a TKI of interest (index TKI) during June 2008-December 2011 were identified from the IMS PharMetrics Plus Health Plan Claims Database for adult patients with CML diagnosis (ICD-9-CM 205.1x), 120 days pre-index continuous enrollment (CE) and no clinical trial participation. Episodes experiencing treatment failure, defined as switch to a non-index TKI or discontinuation of index TKI (gap of ≥ 60 days), and with 1 year CE post-failure, were analyzed. LOT was determined by number of unique TKIs used in the pre-index. All-cause HCRU and costs (2012 USD) in the 1 year post-failure were assessed by LOT, and the comparisons between 1L and 2L failures were also adjusted using multivariate generalized linear models (GLMs) to control for underlying differences. RESULTS: A total of 706 episodes were identified (518 1L; 180 2L; 8 3L). Unadjusted HCRU over 1 year post-failure increased significantly. This was accompanied by a significant increase in unadjusted mean costs for 2L failures vs. 1L failures ($99,624 vs. $78,667, p = 0.021, Δ$20,957). Following the adjustment using GLMs, adjusted mean costs were 38% higher (95% CI 1.14-1.68), driven primarily by use of medical services. In adjusted analyses, compared to 1L, 2L failures had: 45% more ambulatory visits (mean 31 vs. 21, 95% CI 1.26-1.66), 75% higher risk of hospitalization (33% vs. 23% hospitalized, 95% CI 1.16-2.64), and 73% higher medical costs (95% CI 1.31-2.29). Medical costs comprised a greater proportion of total costs in 2L vs. 1L (55% vs. 44%); pharmacy costs did not increase significantly. CONCLUSIONS: The economic burden over 1 year post TKI failure increased with each sequential line of TKI treatment failure.

Economic Burden of Tyrosine Kinase Inhibitor Treatment Failure in Chronic Myeloid Leukemia.

BACKGROUND: The economic burden of tyrosine kinase inhibitor (TKI) treatment failure in chronic myeloid leukemia (CML) is not well understood. The objective of this study was to quantify the economic burden associated with treatment failure versus successfully remaining on TKI therapy. METHODS: Treatment episodes for adult CML patients initiating a TKI of interest (imatinib, dasatinib, or nilotinib; index TKI) during July 1, 2008, to December 31, 2011, with continuous enrollment for ≥ 120 days before and 1 year after the initiation were identified from the IMS PharMetrics Plus Health Plan Claims Database. Eligible episodes of TKI treatment failure were matched to those without failure using propensity scores based on patients' baseline demographic and clinical characteristics. Treatment failure was defined as a switch to a nonindex TKI or discontinuation (gap in pharmacy claims ≥ 60 days) of index TKI over the 1-year follow-up. Mean all-cause health care resource utilization and costs per episode (in 2012 US dollars) over follow-up were compared between failures and nonfailures. RESULTS: Among 1774 eligible episodes, 547 failures were matched to 547 nonfailures. Failures had fewer TKI prescription fills but higher utilization of all other services versus nonfailures. Consequently, failures incurred lower pharmacy costs ($51,238 vs. $72,450; Δ-$21,212) but higher medical costs ($52,619 vs. $18,180; Δ$34,439) than nonfailures, resulting in higher total costs ($103,857 vs. $90,630; Δ$13,227) (all P < .05). CONCLUSION: Total health care costs are higher for episodes of TKI treatment failure than those of ongoing treatment, largely as a result of costly medical (nonpharmacologic) services. Avoiding treatment failure by optimal CML management may reduce health care costs.