Tyrosine Kinase Inhibitor Adherence Research Articles

Older patients with chronic myeloid leukemia face suboptimal molecular testing and tyrosine kinase inhibitor adherence.

Tyrosine kinase inhibitor (TKI) use is critical in the care of patients with chronic myeloid leukemia (CML). Quantitative polymerase chain reaction (qPCR) testing for BCR-ABL1 every 3months during the first year of TKI treatment is recommended to assure achievement of milestone response goals. Real-world evidence for the patterns of qPCR monitoring and TKI adherence in the older patient population is lacking. Using the Surveillance, Epidemiology, and End Results-Medicare database, we identified 1192 patients aged ≥66 years (median age, 74 years) with newly diagnosed CML who were followed up for ≥13months from TKI initiation. In total, 965 patients (81.0%) had ≥1 test, with 425 (35.7%) and 540 (45.3%) of the patients tested during 1, 2, and ≥3 quarters (optimal monitoring) of the first year from TKI initiation, respectively. In multivariable analysis, diagnosis in later years and influenza vaccination before diagnosis, a proxy for health care access, were associated with optimal qPCR monitoring. Use of low-income subsidy and residing in census tracts with the lowest socioeconomic status were associated with less optimal monitoring. Patients with optimal monitoring were 60% more likely to be TKI adherent (odds ratio, 1.60; 95%CI, 1.11-2.31; P= .01) and had improved 5-year survival (hazard ratio, 0.66; 95%CI, 0.49-0.90; P< .01) than those without such monitoring. In this large, real-world study of CML management patterns, many older patients had suboptimal molecular monitoring, which was associated with decreased TKI adherence and worse survival.

Contemporary “Real World” Molecular Testing and Tyrosine Kinase Inhibitor Adherence Patterns Among Older Pts with Chronic Myeloid Leukemia in the United States

Contemporary “Real World” Molecular Testing and Tyrosine Kinase Inhibitor Adherence Patterns Among Older Pts with Chronic Myeloid Leukemia in the United States

A Pharmacist-Led Oral Chemotherapy Program's Impact on Chronic Myeloid Leukemia Patient Satisfaction, Adherence, and Outcomes.

Patients with chronic myeloid leukemia (CML) can be treated with oral tyrosine kinase inhibitors (TKIs). Pharmacist-led oral chemotherapy programs (POCPs) can improve TKI adherence rates, but evaluation of patient satisfaction with such programs is rare. The purpose of this analysis was to compare the satisfaction of patients with CML taking TKIs enrolled in a POCP program with that of those not enrolled. Secondary objectives were to assess adherence rates, patient-reported value, early molecular response (EMR) rates, and major molecular response (MMR) rates. This study utilized an anonymous telephone survey of patients who had taken TKIs for at least 3 months. Molecular response was determined by chart review. Of 40 patients surveyed, 50% were enrolled in the POCP, and the POCP group had more African Americans than the non-POCP group. More patients in the POCP were satisfied with their care than in the non-POCP group (100% vs. 75%, p = .047). There were no differences in high patient-reported adherence (55% vs. 60%, p = 1.000), patient-reported value for integrated services (95% vs. 90%, p = 1.000), achievement of EMR (75% vs. 75%, p = 1.000), or MMR (85% vs. 85%, p = 1.000). Patients in the POCP received more structured clinical pharmacy services; however, both groups felt the clinical pharmacist played a major role in their care (85% vs. 90%, p = 1.000). Patients in the non-POCP group reported lower satisfaction than those enrolled resulting from fragmented care that was likely due to external specialty pharmacies. Irrespective of POCP enrollment, patients reported clinical pharmacists play a major role in their therapy and value integration of their specialty pharmacy and medical team.

Out-of-Pocket Costs for Tyrosine Kinase Inhibitors and Patient Outcomes in EGFR- and ALK-Positive Advanced Non-Small-Cell Lung Cancer.

We investigated the association of out-of-pocket (OOP) costs for tyrosine kinase inhibitors (TKIs) with overall survival (OS) in epidermal growth factor receptor (EGFR)- and anaplastic lymphoma kinase (ALK)-positive advanced non-small-cell lung cancer (NSCLC). We secondarily investigated associations of TKI OOP costs with TKI adherence, duration of therapy (DOT), and TKI discontinuation. We used the Hutchinson Institute for Cancer Outcomes Research registry-claims database to identify patients with stage IV EGFR- or ALK-positive NSCLC; ≥ 1 claims for EGFR or ALK TKIs; and ≥ 3-month survival from TKI initiation. We estimated the average monthly TKI OOP costs per patient up to 3 months from TKI initiation, categorizing patients into quartiles of TKI OOP costs (Q1 < Q2 < Q3 < Q4). We conducted landmark analysis at 3 months from TKI initiation to compare Q1-3 v Q4 TKI OOP costs with respect to OS, TKI DOT, TKI adherence, and TKI discontinuation. Seventy-eight and twenty-seven patients comprised the Q1-3 and Q4 groups, respectively. Median monthly TKI OOP costs were $1,431 (Q1-3) v $2,888 (Q4). Compared with Q1-3, Q4 patients had inferior OS (adjusted hazard ratio [HR], 1.85; [95% CI, 1.11 to 3.10], similar TKI DOT (adjusted HR, 1.06; 95% CI, 0.53 to 2.15), decreased TKI adherence (adjusted odds ratio [OR], 0.28; 95% CI, 0.10 to 0.76), and higher TKI discontinuation rate (adjusted OR, 8.75; 95% CI, 2.59 to 29.52). Among patients with advanced EGFR- and ALK-positive NSCLC, higher TKI OOP costs are associated with decreased TKI adherence, a higher likelihood of TKI discontinuation, and inferior survival.

Predictors of tyrosine kinase inhibitor adherence trajectories in patients with newly diagnosed chronic myeloid leukemia.

Although consistent use of tyrosine kinase inhibitors (TKIs) confers significant improvements in long-term survival for individuals with chronic myeloid leukemia (CML), only 70% of CML patients are adherent to TKIs. Understanding the factors that contribute to non-adherence and establishing dynamic adherence patterns in this population are essential aspects of targeted drug monitoring and intervention strategies. Newly diagnosed CML patients were identified in the MarketScan database and relevant covariate values extracted. Proportion of days covered (PDC) per 30-day interval was used to calculate adherence over a 12-month follow-up period. We conducted a latent profile analysis (LPA) on these PDC estimates to identify distinct, dynamic patterns of TKI adherence. Identified trajectories were grouped into four clinically relevant categories and predictors of membership in these categories were determined via multinomial logistic regression. Four broad adherence categories were identified from the LPA: never adherent, initially non-adherent becoming adherent, initially adherent becoming non-adherent, and stable adherent. Results from the subsequent multinomial logistic regression indicated that younger age, female sex, greater monthly financial burden, fewer comorbidities, fewer concomitant medications, year of diagnosis, higher starting dose, TKI type, and a longer duration from diagnosis to treatment were significantly associated with membership in at least one of the three non-stable adherent groups. Select sociodemographic and clinical characteristics were found to predict membership in clinically meaningful groups of longitudinal TKI adherence. These findings could have major implications for informing personalized monitoring and intervention strategies for individuals who are likely to be non-adherent.

Adherence trajectories in oral therapy for chronic myeloid leukemia: Overview of a research protocol.

Over a quarter of chemotherapy regimens now include oral agents. Individuals living with cancer are now responsible for administering this lifesaving therapy at home by taking every dose as prescribed. One type of oral chemotherapy, tyrosine kinase inhibitors (TKIs), is the current recommended treatment for chronic myeloid leukemia. This targeted therapy has markedly improved survival but comes with significant side effects and financial costs. In the study described in this protocol, the investigators seek to understand the dynamic nature of TKI adherence experienced by individuals diagnosed with CML. Using a mixed-method approach in this prospective observational study, funded by the National Cancer Institute, we seek to describe subjects' adherence trajectories over 1 year. We aim to characterize adherence trajectories in individuals taking TKIs using model-based cluster analysis. Next, we will determine how side effects and financial toxicity influence adherence trajectories. Then we will examine the influence of TKI adherence trajectories on disease outcomes. Additionally, we will explore the experience of patients taking TKIs by interviewing a subset of participants in different adherence trajectories. The projected sample includes 120 individuals taking TKIs who we will assess monthly for 12 months, measuring adherence with an objective measure (Medication Event Monitoring System). Identifying differential trajectories of adherence for TKIs is important for detecting subgroups at the highest risk of nonadherence and will support designing targeted interventions. Results from this study can potentially translate to other oral agents to improve care across different types of cancer.

Multi-center observational study on the adherence, quality of life, and adverse events in lung cancer patients treated with tyrosine kinase inhibitors.

Cancer patients tend to prefer oral instead of parenteral chemotherapy. To date, there is little evidence on the medication adherence in cancer patients. We investigated medication adherence to tyrosine kinase inhibitors in patients suffering from non-small cell lung cancer. Tyrosine kinase inhibitor adherence was measured electronically by MEMS® (medication event monitoring system) over at least six months. Adherence rates were calculated in terms of Dosing Compliance, Timing Compliance, Taking Compliance, and Drug Holidays. Patients were dichotomized as adherent when Dosing Compliance and Timing Compliance were ≥80%, Taking Compliance ranged between 90 and 110%, and <1 Drug Holiday was registered. Quality of life was assessed by two questionnaires (EORTC QLQ-C30 version 3.0, EORTC QLQ-LC13) at three time points. Adverse drug events were reported via patient diaries. Out of 32 patients enrolled, data from 23 patients were evaluable. Median Dosing Compliance, Taking Compliance, and Timing Compliance adherence rates of tyrosine kinase inhibitor intake amounted to 100%, 98%, and 99%, respectively; Drug Holidays were observed in three patients. Four patients were dichotomized as non-adherent. Three of them had a twice-daily tyrosine kinase inhibitor regimen. Median quality of life scores amounted to 67 (max. 100) and remained unchanged over the study period. Fatigue and rash were the most frequently reported adverse drug events. Medication adherence of non-small cell lung cancer patients treated with tyrosine kinase inhibitors was extraordinarily high and is likely to support the effectiveness of tyrosine kinase inhibitor treatment and a good quality of life over a long period of time. Adherence facilitating information and education is especially relevant for patients taking tyrosine kinase inhibitors in a twice-daily regimen.

PCN217 THE IMPACT OF ORAL ONCOLYTIC PARITY LEGISLATION ON ADHERENCE AND OUT-OF-POCKET SPENDING IN CHRONIC MYELOID LEUKEMIA

To compare changes in adherence and out-of-pocket costs among patients with chronic myeloid leukemia (CML) before and after state-level oral oncolytic parity laws, which require that oral oncolytics under the pharmacy benefit are covered similarly to parenteral oncolytics under the medical benefit. Adults with CML, ≥1 pharmacy claim for a tyrosine kinase inhibitor (TKI) and residence in any of 41 states that implemented oral oncolytic parity legislation between 1-1-2007 and 12-31-2017 were identified from the IBM® MarketScan® Commercial Claims Database. Continuous enrollment 3 months before and 6 months after the first TKI claim date (index date) was required. The proportion of days covered (PDC) was calculated and 30-day out-of-pocket costs (copayments, coinsurance, and deductibles as 2017 United States dollars) were assessed in the 6 months post-index; patients with a PDC ≥0.85 were categorized as adherent. Differences in outcomes before and after parity were evaluated, controlling for membership in health plans subject to parity (fully-insured health plans [FIHPs]) or not (self-funded health plans [SFHPs]). Of 1,887 CML patients initiating a TKI, 678 (35.9%) were members of FIHPs and 1,209 (64.1%) of SFHPs. After parity, mean PDC improved in FIHPs and SFHPs (0.85 to 0.87 and 0.87 to 0.90, respectively). TKI adherence improved from 69.2% to 73.2% of patients in FIHPs (P=0.2817) and similarly from 73.6% to 78.3% in SFHPs (P=0.0585). In FIHPs, median (Q1–Q3) out-of-pocket costs per-patient increased from $33.48 ($18.12–$63.41) to $37.78 ($5.35–$112.03), while in SFHPs they increased from $38.26 ($23.69–$85.27) to $52.84 ($19.05–$112.03). Oral oncolytic parity legislation has produced minimal impact on TKI adherence and out-of-pocket costs among CML patients. To improve clinical outcomes and protect patients from rising out-of-pocket costs, policymakers may consider amending current legislation.

Tyrosine Kinase Inhibitors and the Relationship With Adherence, Costs, and Health Care Utilization in Commercially Insured Patients With Newly Diagnosed Chronic Myeloid Leukemia: A Retrospective Claims-Based Study.

To examine the association among tyrosine kinase inhibitor (TKI) out-of-pocket costs, adherence, and health care costs and utilization in a large group of commercially insured patients with chronic myeloid leukemia (CML). Patients with CML aged 18 to 64 years were identified using IBM MarketScan Commercial Database between April 1, 2011 and December 31, 2014. Patients were required to be continuously enrolled 3 months before and 12 months after TKI (imatinib, dasatinib, or nilotinib) initiation. TKI adherence is estimated using the proportion of days covered (PDC), defined as the percentage of the PDC by the prescription fill during the 12-month study period (adherent patients have PDC ≥80%). Health care cost differences between adherent and nonadherent patients were estimated using generalized linear models. Health care utilization was compared using negative binomial regression models. All models were controlled for potential confounding factors. The study sample consisted of 863 patients, where 355 (41.1%) patients were classified as adherent. Over the study period, nonadherent patients incurred US$10,974 more in medical costs (P<0.001), and US$1663 more in non-TKI pharmacy costs (P<0.01). Adherent patients incurred US$28,184 more in TKI pharmacy costs (P<0.001) that resulted in US$18,305 more in overall total health care costs (P<0.001). Adherent patients, however, were estimated to be less likely to have all-cause hospitalizations (incidence rate ratio, 0.32; P<0.001), or CML-specific hospitalizations (incidence rate ratio, 0.31; P<0.01). Patients with CML with better adherence experienced fewer hospitalizations, resulting in medical service cost savings. These lower medical costs, however, were more than offset by higher TKI medication costs observed during the first year of TKI therapy.

Treatment patterns and healthcare costs among newly-diagnosed patients with chronic myeloid leukemia receiving dasatinib or nilotinib as first-line therapy in the United States

Objective: To compare treatment patterns and economic outcomes of dasatinib and nilotinib as 1st-line therapies for chronic myeloid leukemia (CML).Methods: Adult CML patients initiated on first-line dasatinib or nilotinib in 2010–2014 were identified from two large US administrative claims databases. Treatment patterns, tyrosine kinase inhibitor (TKI) adherence and healthcare resource utilization (HRU) and costs were measured from the 1st-line TKI initiation (index date) to the end of follow-up.Results: A total of 604 and 418 patients were included in the dasatinib and nilotinib cohorts (mean ages = 50.9 and 52.5 years, 46.4% and 45.7% female), respectively. Among the dasatinib patients, 91% started with 100 mg/day, 3% with <100 mg/day, and 6% with >100 mg/day. Among the nilotinib patients, 76% started with 600 mg/day, 16% with >600 mg/day, and 8% <600 mg/day. The dasatinib cohort had a higher hazard of dose decrease (hazard ratio [HR] = 1.66; p = .002) and of switching to another TKI (HR =1.62; p = .019) compared to the nilotinib cohort. The hazard of dose increase (HR =0.76; p = .423) and treatment discontinuation (HR =1.10; p = .372) were not significantly different between cohorts. There was also no significant difference in TKI adherence levels (mean proportion of days covered [PDC] difference over first 6 months = −0.0003, p = .981; mean PDC difference over first 12 months = −0.0022, p = .880) and HRU (inpatient day incidence rate ratio [IRR] = 1.03, p = .930; emergency room IRR =1.26, p = .197; and days with outpatient services IRR = 1.01, p = .842). The dasatinib cohort incurred higher healthcare costs by $749 per patient per month (p = .044) compared to the nilotinib cohort.Limitation: Information on CML phase and Sokal score was not available.Conclusions: Dasatinib was associated with an increased hazard of dose decrease and switching to another TKI and higher healthcare costs, vs nilotinib.

Impact of oncology pharmacist-managed oral anticancer therapy in patients with chronic myelogenous leukemia.

Studies have identified non-adherence as one of the major contributing factors to treatment failure in chronic myelogenous leukemia (CML) patients receiving imatinib. Published literature has demonstrated a unique role of oncology pharmacists, as part of a multidisciplinary team, in contributing to overall positive outcomes for patients. To evaluate the impact of an oncology pharmacist-managed oral anticancer therapy program on oral medication adherence in CML patients versus usual care. Electronic refill history and medical records of patients diagnosed with CML treated with oral tyrosine kinase inhibitors (TKIs) managed by oncology pharmacists during a 6-year period, were retrospectively reviewed. Imatinib adherence rate, as the primary endpoint, was compared with the rate for those in the usual care group within the same organization. The secondary endpoints were descriptive to characterize pharmacist interventions for all TKIs. A total of 56 patients including 45 who were treated with imatinib, were evaluated. The group managed by oncology pharmacists resulted in a higher percentage of imatinib adherence rate compared to usual care (88.6% vs 65.8%, p = 0.0046). A total of 3432 pharmacist encounters were reviewed, and 567 interventions of six categories including side effect monitoring/management (n = 95; 16.8%); drug interaction detection (n = 109; 19.2%); TKI dose adjustment (n = 82; 14.5%); laboratory monitoring (n = 200; 35.3%); non-CML related drug choice (n = 74; 13.1%); and copay assistance (n = 7; 1.2%), were documented. This resulted in a mean of 10.1 interventions per patient. Our oncology pharmacist-managed oral anticancer therapy program significantly improved TKI adherence rates in CML patients. We attribute the success of our program to consistent follow-up by utilizing routine phone, and secure email follow-ups, that allowed our oncology pharmacists to build a close and trustworthy relationship with patients and families.

Treatment-adherence beliefs and behaviors in patients with chronic myeloid leukemia (CML).

9558 Background: Tyrosine kinase inhibitors (TKIs) are effective yet chronic indefinite therapy for CML. Strong links exist between TKI adherence and optimal outcomes. Suboptimal adherence is common, affecting clinical outcomes and healthcare costs. Nonadherent patients underrecognize missed-dose impact on response. This study explored the link between belief and behavior vis-a-vis adherence. Methods: With outreach to online, national and community networks from 10/13 to 7/14, 484 CML patients enrolled in the Cancer Experience Registry: CML, an online project to advance CML knowledge and patient engagement. 393 (81%) completed a web-based survey including questions assessing accord with 2 statements (1) It is okay to miss a dose of my CML medicine every now and then, and (2) I need to take every dose of my CML medicine or it might not work; as well, participants reported missed TKI-dose frequency. Logistic regression was used to study the beliefs-behavior link among US patients taking TKIs (n = 318). Regr...

Medication Adherence in Patients with Chronic Myelogenous Leukemia Using Tyrosine-Kinase Inhibitors: A Retrospective Analysis

Abstract INTRODUCTION: Suboptimal adherence to medication is a serious issue in the management of chronic myeloid leukemia (CML) and contributes to worse clinical outcomes for patients. (Noens L, et al. Blood. 2009;113(22):5401-11.) The objective of this analysis is to evaluate adherence to treatment of patients diagnosed with CML and exposed to the tyrosine-kinase inhibitors (TKIs) imatinib, dasatinib or nilotinib and to analyze CML-related hospitalizations costs across adherence levels. METHODS: De-identified data from hospital databases and haematology files from 4 Italian sites were combined to select adult patients diagnosed with CML, newly treated with imatinib, dasatinib, or nilotinib from July 2009 until June 2012 (inclusion period). Newly treated patients were identified by the absence of previous prescriptions. Demographics and clinical characteristics were assessed at the date of the first prescription within the inclusion period. Adherence to TKIs was measured as proportion of days covered (PDC) over a 180-day period. (Wu EQ, et al. Curr Med Res Opin. 2010;26(12):2861-9.) PDC was computed as the actual number of days of TKI therapy supplied divided by 180, and multiplied by 100. Days' supply was calculated based on quantity dispensed and dosage unit per day prescribed to patients (a dose of 100 mg for dasatinib, 400 mg for imatinib and 800 mg for nilotinib). PDC (and, therefore, adherence) was categorized using standard thresholds: ≥80% (‘fully adherent'), 40%–79% (‘partially adherent'), and &lt;40% (‘non-adherent'). (Rasmussen JN, et al. JAMA. 2007;297(2):177-86.) The average daily dose was also calculated dividing the total dose dispensed by the number of days of TKI therapy supplied. A multivariable logistic regression model was used to estimate the relationship between TKI therapy and adherence, controlling for age, gender, Charlson comorbidity index, prior use of antihypertensives, drugs for acid-related disorders and anti-inflammatory drugs and previous hospital discharges for cancer other than CML. Leukemia-related hospitalizations were also collected. The ethics committees for the local health units approved the study. RESULTS: We identified 88 CML newly treated imatinib patients, 59 newly treated dasatinib patients and 50 newly treated nilotinib patients. Age, gender, Charlson comorbidity index and the prior use of the drug treatments listed above were similar at baseline. Dasatinib patients had fewer previous hospital discharges for cancer (P&lt;0.001). As indicated in Figure 1, dasatinib newly treated patients were more adherent than imatinib- and nilotinib-naïve patients (86.4% vs 76.9% and 46.0% respectively; P&lt;0.001). Figure 1. Percentage of adherent patients (PDC≥80%) across the TKI therapy groups. Figure 1. Percentage of adherent patients (PDC≥80%) across the TKI therapy groups. The mean daily dose calculated on the basis of the adherence was 377 mg for imatinib, 97 mg for dasatinib and 676 mg for nilotinib. Comparing with dasatinib, multivariate logistic regression found significantly lower rates of adherence for imatinib (P=0.026) and for nilotinib (P&lt;0.001), odds ratios (95% confidence intervals) resulted respectively of 0.24 (0.07-0.84) and of 0.10 (0.03-0.32). Independent of medication, higher adherence was associated with lower leukemia-related hospitalizations costs (the average cost per patient was €3,567 where PDC was 40%-79% and €554 where PDC≥80%). In addition, analyses were stratified by the presence or absence of previous hospital discharges for cancer. Among the 7 patients with previous hospital discharges for cancer, the average cost per patient was €6,935 where PDC was 40%-79% and €983 where PDC≥80%; while among the 190 patients with no previous hospitalizations for cancer, the average cost per patient was €536 where PDC was 40%-79% and €207 where PDC≥80%, confirming our findings in both cohorts. CONCLUSIONS: This study showed that CML patients newly treated with imatinib or nilotinib were significantly less adherent than patients receiving dasatinib. On average, lower adherent patients had higher leukemia-related hospitalization costs. Further research is necessary to understand the relationship between adherence level and treatment response. Disclosures No relevant conflicts of interest to declare.

Association between regular molecular monitoring and tyrosine kinase inhibitor therapy adherence in chronic myelogenous leukemia in the chronic phase

Objective:Adherence with oral tyrosine kinase inhibitor (TKI) therapy over prolonged timeframes is required for successful outcomes among patients with chronic phase chronic myelogenous leukemia (CP-CML). Since quantitative polymerase chain reaction (qPCR) monitoring may identify early suboptimal responses, and thereby permit detection of non-adherence to therapy, we sought to assess the association between frequency of molecular monitoring and medication adherence.Research design and methods:This is a retrospective cohort study design of diagnosed CP-CML obtained from two large US administrative claims databases. Patients were grouped into cohorts based on the number of qPCR tests they had. Adherence was assessed both by medication possession ratio (MPR) and proportion of days covered (PDC) and was compared between qPCR cohorts. A sensitivity analysis was performed by adjusting for the number of oncology outpatient visits not due to routine molecular monitoring.Results:Over the 12 month study period, 1205 CML patients met the selection criteria; 41.0% had no qPCR tests, 31.9% had 1–2 tests, and 27.1% had 3–4 tests; 88.9% of patients were initiated on imatinib. Patients in the 3–4 qPCR tests cohort had an average MPR that was 10.22 (p < 0.001) and 9.54 (p < 0.001) percentage points higher compared to patients in the 0 tests cohort and the 1–2 tests cohort. When using PDC as a measure of adherence, similar results were obtained. The results of the sensitivity analysis were consistent with core analysis findings, excluding number of physician visits as a potential driver of adherence.Limitations:These findings demonstrate an association, not causation, between molecular monitoring frequency and adherence.Conclusions:Frequent molecular monitoring (3–4 times per year as recommended in current guidelines) is associated with greater TKI treatment adherence for patients diagnosed with CML. Since TKI adherence >80% has been associated with better clinical outcomes, this study underscores the importance of molecular monitoring.

Medication adherence among adults prescribed imatinib, dasatinib, or nilotinib for the treatment of chronic myeloid leukemia

Oral tyrosine kinase inhibitors are the standard of care for chronic myeloid leukemia. Tyrosine kinase inhibitors are administered in an outpatient setting for an indefinite period which may negatively impact adherence. Non-adherence to tyrosine kinase inhibitors is associated with disease progression. To evaluate the need for adherence-enhancing interventions, this study was designed to determine the proportion of chronic myeloid leukemia patients non-adherent to their tyrosine kinase inhibitor regimen. The secondary objective was to identify the influence of patient characteristics on tyrosine kinase inhibitor adherence. Cross-sectional retrospective chart and dispensing record reviews were performed to identify patients receiving a tyrosine kinase inhibitor from 1 June 2010 to 31 January 2012. Adherence was evaluated using the medication possession ratio. A total of 124 patients were included. Thirty-eight (31%) patients were non-adherent to their tyrosine kinase inhibitor regimen. Patients not receiving concurrent medications were more likely to be non-adherent (odds ratio (OR) 2.33, 95% confidence interval (CI) 1.05-5.13, p=0.04). The median medication possession ratio was 0.95 (IQR=0.83-1.07). Median medication possession ratio was lower in patients receiving imatinib compared to dasatinib or nilotinib (0.95 vs. 1.00, p=0.01) and in those less than 50 years old compared to those greater than 50 years old (0.92 vs. 0.97, p=0.02). Optimal tyrosine kinase inhibitor adherence in chronic myeloid leukemia patients poses a significant obstacle in achieving best possible outcomes while reducing healthcare costs. In this study, one in three chronic myeloid leukemia patients treated with a tyrosine kinase inhibitor were non-adherent to their regimen. Those at higher risk of non-adherence were on no concurrent medications, less than 50 years old, and those treated with imatinib. Active intervention to improve tyrosine kinase inhibitor adherence should be developed, implemented, and evaluated to improve patient outcomes at our center.

Cost Sharing and Adherence to Tyrosine Kinase Inhibitors for Patients With Chronic Myeloid Leukemia

The introduction of imatinib, a tyrosine kinase inhibitor (TKI), has greatly increased survival for patients with chronic myeloid leukemia (CML). Conversely, nonadherence to imatinib and other TKIs undoubtedly results in disease progression and treatment resistance. We examined trends in imatinib expenditures from 2002 to 2011 and assessed the association between copayment requirements for imatinib and TKI adherence. We used MarketScan health plan claims from 2002 to 2011 to identify adults (age 18 to 64 years) with CML who initiated imatinib therapy between January 1, 2002, and June 30, 2011, and had insurance coverage for at least 3 months before through 6 months after initiation (N = 1,541). Primary outcomes were TKI discontinuation and nonadherence. The primary independent variable was out-of-pocket cost for a 30-day supply of imatinib. By using a propensity-score weighted sample, we estimated the risk of discontinuation and nonadherence for patients with higher (top quartile) versus lower copayments. Monthly copayments for imatinib averaged $108; median copayments were $30 (range, $0 to $4,792). Mean total monthly expenditures for imatinib nearly doubled between 2002 and 2011, from $2,798 to $4,892. Approximately 17% of patients with higher copayments and 10% with lower copayments discontinued TKIs during the first 180 days following initiation (adjusted risk ratio [aRR], 1.70; 95% CI, 1.30 to 2.22). Similarly, patients with higher copayments were 42% more likely to be nonadherent (aRR, 1.42; 95% CI, 1.19 to 1.69). Patients with higher copayments are more likely to discontinue or be nonadherent to TKIs. Given the importance of these therapies for patients with CML, our data suggest a critical need to reduce patient costs for these therapies.

Association Between Treatment Adherence and Response Among Patients With Chronic Myeloid Leukemia (CML) Receiving First-Line TKIs In The Community Setting

BackgroundAvailability of the tyrosine kinase inhibitors (TKIs) has revolutionized the outcome of patients with CML, with a 10-year overall survival rate of approximately 90%. This long-term benefit is highly dependent upon adherence; patients with less than 90% TKI adherence have been shown to have poor outcomes. The primary aim of this retrospective observational study is to determine the association between adherence to first-line TKIs and response in community-based CML patients. The secondary aim is to describe the real-world effectiveness of first-line TKIs by evaluating rates of response and disease progression. MethodsThe McKesson Specialty Health/US Oncology Network (USON) iKnowMed (iKM) electronic health record (EHR) database and medical charts were used to identify newly diagnosed CML patients who received first-line TKIs between July 2007 and March 2011. Adherence to TKI was measured as proportion of days covered (PDC). PDC was computed as the actual number of days of TKI therapy divided by the number of follow-up days after TKI initiation. Adherence was defined as PDC ≥90%. Response assessment included complete hematologic response (CHR) at 3 and 6 months (mo), complete cytogenetic response [CCyR (FISH or karyotype)] at 12 and 18 mo, and major molecular response [MMR (BCR-ABLIS ≤0.1% or ≥3 log reduction)] at 12 and 18 mo. Disease progression was defined as transformation to accelerated phase (AP) or blast phase (BP) CML, bone marrow transplant (BMT), or all-cause of death during follow-up. Descriptive analysis was conducted to summarize baseline patient characteristics and progression. Fisher's exact test will be used to determine univariate association between adherence and response. Here we report the interim results for imatinib adherence and treatment response. Data collection for dasatinib/nilotinib is ongoing and will be presented. ResultsThree-hundred newly diagnosed CML patients were identified within the iKM database (195 imatinib, 54 dasatinib, and 51 nilotinib). Among 218 patients evaluated thus far, 155 (71.1%) received imatinib, 28 (12.8%) received dasatinib, and 35 (16.1%) received nilotinib. Baseline patient characteristics were well balanced across the TKIs. Mean PDC for imatinib was 80%; 58% (n=117) were adherent (PDC≥90%). Imatinib treatment response data is presented in Table 1 according to adherence status. Low frequency of response monitoring limited the number of patients for analysis (47% evaluable for cytogenetic response and 67% for molecular response within the first 18 mo of treatment). Within a median follow-up of 38 mo, 25 (16%) imatinib patients progressed during the follow-up period (9 transformed to AP/BP, 4 BMT, 12 deaths). Overall, there were 14 deaths among imatinib treated patients.Table 1Imatinib adherence and response dataCHR 6 moCCyR 12 moCCyR 18 moMMR 12 moMMR 18 moOverall patients tested (n)102647398104Patients who achieved response, n (%)89 (87)33 (51)42 (57)22 (22)34 (32)Patients tested and evaluated for adherence (n)8348557579Total number of patients who achieved response7323302029- Adherent patients who achieved response, n (%)51 (91)14 (56)19 (65)14 (31)21 (45)- Non-adherent patients who achieved response, n (%)22 (81)9 (39)11 (42)6 (19)8 (24) ConclusionAmong newly diagnosed CML patients who received imatinib in a community practice setting, the rates of 12-mo CCyR and MMR were 51% and 22%, respectively. In addition, 16% of imatinib-treated patients progressed during a median follow-up period of 38 mo. Fifty-eight percent of imatinib patients were adherent; these patients were observed to have higher cytogenetic and molecular responses compared to non-adherent patients. Response assessment within this study was limited by the low frequency of cytogenetic and molecular monitoring within clinical practice; USON is initiating measures to improve compliance to response monitoring guidelines. Disclosures:Bhowmik:McKesson Specialty Health/US Oncology Network: Employment. Bhor:McKesson Specialty Health/US Oncology Network: Employment. Yap:McKesson Specialty Health/US Oncology Network: Employment. Middlebrook:McKesson Specialty Health/US Oncology Network: Employment. Rembert:McKesson Specialty Health/US Oncology Network: Employment. Cain:Bristol-Myers Squibb: Employment. Okoro:Bristol-Myers Squibb: Employment. Bolinder:Bristol-Myers Squibb: Employment. Jabbour:Bristol-Myers Squibb: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Ariad: Honoraria.