ALBERT

Beschreibung: Abstract 4758 Background: Nilotinib and dasatinib are second-generation tyrosine kinase inhibitors (TKI) indicated for the treatment of chronic phase (CP) and accelerated phase (AP) Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML) patients resistant to or intolerant of first-line therapy with imatinib. Dasatinib is also indicated for treatment of blast crisis (BC) patients. The recommended dose of nilotinib for treatment of resistant or intolerant Ph+ CML-CP is 400 mg twice daily. The current recommended starting dose of dasatinib for second-line therapy of Ph+ CML-CP is 100 mg once daily, and for Ph+ CML-AP or BC is 140 mg once daily. Some patients may experience treatment-related adverse events at the recommended doses of nilotinib or dasatinib, necessitating a dose reduction or interruption of treatment. Therefore, patients may not be receiving the full approved therapeutic doses. There is no available information comparing dose modifications or interruption of treatment between nilotinib and dasatinib. The objective of this study was to compare the frequency of dose adjustments and treatment interruptions between nilotinib and dasatinib in second-line therapy in CML patients from a clinical practice setting perspective. Methods: Two claims databases were combined (MarketScan and Ingenix Impact, 01/2002-12/2008) to identify patients diagnosed with CML (ICD-9 code 205.1x) and who had received ≥1 prescription of nilotinib or dasatinib. Patients were required to have continuous enrollment ≥1 month prior to and after the index date. The index date was defined as the first prescription for nilotinib or dasatinib. Two patient cohorts were created based on patient's index treatment. Dasatinib data prior to the 100 mg once daily approval date were excluded from the analysis. Patients were followed for up to 6 months from the index date to the earliest of the termination of health care plan enrollment, or end of data availability. Dosage characteristics, including any dose changes from index prescription, defined as either an increase or decrease in the delivered dose and average dose were calculated during the study period. A ≥15% dose decrease in average dose is selected for comparison between the two groups as it is the mean of the lowest absolute dose change. Dose adjustments were further characterized in relation to the incidence and frequency of hematological and non-hematological events during the study period. Results: Data were analyzed for 514 patients receiving a second-line TKI (67 nilotinib, 447 dasatinib). Baseline characteristics were similar between the groups. Seven patients (2 nilotinib, 5 dasatinib) were excluded due to missing dosage information. Patients treated with dasatinib had more follow-up days in the study period than nilotinib-treated patients (mean ± standard deviation [SD], 162 ± 39 days versus 143 ± 51 days; P = 0.0003). There were no differences between the number of patients treated with nilotinib or dasatinib who had any dose adjustments over the study period (P = 0.8424). Stratification of the data by percent of adjustment revealed statistically significant differences between the two treatment groups. Eighty-nine (19.9%) patients treated with dasatinib had at least one dose reduction of at least 15% compared with 4 patients (6.0%) treated with nilotinib (P = 0.0057). Dasatinib-treated patients with at least 15% dose reduction experienced a mean ± SD of 0.24 ± 0.52 dose decreases compared with 0.06 ± 0.24 dose decreases for patients who received nilotinib (P = 0.0055). However the time to first dose reduction was longer for dasatinib users than for nilotinib users (15.1 ± 37.5 days vs. 7.5 ± 31.5 days, P = 0.0194). Dose decreases occurred within 30 days of a hematological or non-hematological event in 49.5% of patients. Conclusion: These data demonstrate that more CML patients treated second-line with dasatinib experienced dose reductions of at least 15% than patients treated second-line with nilotinib, and that fewer dose reductions were required by the nilotinib users. Although this study did not assess the specific reasons for dose change, dose reductions are frequently associated with hematological or non-hematological events. Future studies may also investigate the relationship between response to treatment and dose reduction for the two TKIs. Disclosures: Yu: Analysis Group, Inc.: Employment. Guerin:Analysis Group, Inc.: Employment. Bollu:Novartis: Employment. Cloutier:Analysis Group, Inc.: Employment. Williams:Novartis: Employment, Equity Ownership.

Beschreibung: Abstract 3841 Background: Ph+ CML patients may develop PE, as an adverse event of some tyrosine kinase inhibitors (TKI) drug therapy. PE is characterized by an excessive accumulation of fluid in the fluid-filled space that surrounds the lungs. PE requires medical care, may compromise the course of CML treatment, and have economic consequence beyond the costs of treating PE. Aim: To compare healthcare resource utilization and costs between CML patients treated with a TKI who developed PE and their matched PE-free controls. Methods: MarketScan and Ingenix Impact databases (2001-2009) were combined to identify adult CML patients (ICD-9CM code 205.1×) who received ≥1 prescription of imatinib, dasatinib, or nilotinib before the index date and had continuous enrollment ≥6 months prior to and after the index date. The index date was defined as 30 days before the first PE diagnosis (ICD-9CM code 511.9×) for patients with PE and was randomly selected among all the eligible calendar dates (i.e., following a prescription for a TKI and a diagnosis for CML) for the PE-free controls. Patients were followed for 6 months after the index date. PE and PE-free patients were matched on a 1:1 ratio using propensity score matching. PE-related (i.e., medical claims with a PE diagnosis) resource utilization (inpatient [IP], outpatient [OP], emergency room [ER] and other medical visits) and costs were estimated for PE patients. To estimate the overall incremental impact of PE, all-cause and CML-related (i.e., medical services associated with a diagnosis code of 205.1×) resource utilization and costs were compared between PE and PE-free controls. All costs were reported in 2009 US dollars. Incidence rate ratios (IRR) for healthcare resource utilization were estimated by Poisson regression models. Incremental costs were estimated using generalized linear models or two-part models. Multivariate regression models controlled for age, gender, treatment duration with tyrosine kinase inhibitor, other chemotherapy, bone marrow or stem cell transplant, CML complexity, Charlson comorbidity index, adverse events, and comorbidities. Results: The study included 179 matched pairs. On average, patients were 63.4 and 63.8 years old with 41% and 49% of the population being female for PE-free and PE patients, respectively. During the study period, PE patients were estimated to have an average of 0.62 PE-related IP admissions, 8.43 IP days, 0.06 ER admissions, and 1.76 OP visits. Compared to PE-free patients, PE patients had more than 7 times as many IP days (IRR=7.23; p

Beschreibung: Abstract 1956 Introduction: Zoledronic acid (ZOL) is currently the standard of care to reduce/delay progressive skeletal-related events (SREs) in multiple myeloma (MM). However, limited evidence is available on the relationship between the timing of ZOL initiation and patient outcomes in this indication. This study retrospectively compared the risks of SREs and ZOL treatment discontinuation associated with early versus delayed ZOL therapy for patients with symptomatic MM. Methods: Data were collected from a physician-administered medical chart review among patients with a confirmed diagnosis of symptomatic MM treated after 01/01/2002. Participating hematologists and oncologists were asked to provide detailed information for patients meeting the inclusion criteria, including demographics, comorbidity profiles, disease severity and bone health at diagnosis, bisphosphonate treatment patterns, and timing of SREs. Analyses were conducted among patients who received early or delayed ZOL therapy, defined respectively as initiating ZOL ≤60 days versus 〉60 days after the first symptomatic MM diagnosis. Kaplan-Meier analysis with a log-rank test was performed to compare the risk of SREs between the study cohorts. Patients were followed from their diagnosis date until the first subsequent SRE, or until loss of follow-up. SREs included pathologic fractures (vertebral or non-vertebral), spinal cord compression, radiation to relieve bone pain, hypercalcemia, and prophylactic surgery to treat impending fractures. Cox proportional hazard modeling was used to compare the risk of SREs associated with early versus delayed ZOL treatment, controlling for demographic factors, stage of MM, bone health status, and presence of major comorbidities at diagnosis. To evaluate the implications of early treatment on persistence, risk of ZOL discontinuation was compared between the cohorts in a survival analysis framework. Time to discontinuation for any reason was evaluated using the Kaplan-Meier method, which followed patients from the date of ZOL initiation; as a sensitivity analysis, time to discontinuation for reasons other than stable or remitted MM was also assessed. Results: A total of 312 patients met the study inclusion criteria. Median time to ZOL initiation from symptomatic MM diagnosis was 25 days in the early treatment cohort (N=126) and 242 days in the delayed treatment cohort (N=186). Baseline characteristics assessed at the time of diagnosis were generally well-balanced between the study groups; however, patients with early ZOL therapy were older on average (62.3±10.0 vs. 60.1±10.6 years; p=.022), were more likely to have Durie-Salmon stage III MM (57.9% vs. 44.1%; p=.034), and had a higher average number of lytic lesions (7.1±7.8 vs. 4.8±7.0; p

Beschreibung: Abstract 3437 Background: The recommended treatment option for patients diagnosed with chronic myeloid leukemia (CML) who do not achieve hematological or cytogenetic response to first-line imatinib therapy is to switch to one of the two new BCR-ABL tyrosine kinase inhibitors, nilotinib or dasatinib. Both drugs appear to be efficacious; however, there are no direct comparisons for treatment adherence between nilotinib and dasatinib. Analysis of adherence may reveal whether these two drugs are being used as intended and how adherence issues may potentially affect clinical outcomes. Previously, higher imatinib adherence was associated with significantly lower utilization of resources and costs. (Wu EQ, et al. Curr Med Res Opin. 2010;26:61-69.) The objective of this retrospective study was to compare adherence associated with second-line nilotinib versus dasatinib in a real-world setting. Methods: Two administrative claims databases were combined (MarketScan and Ingenix Impact, 01/2002-12/2008) to identify patients diagnosed with CML (ICD-9 code 205.1x) who had received ≥1 prescription for either nilotinib or dasatinib. Patients were required to have continuous enrollment ≥1 month prior to and after the index date. The index date was defined as the first prescription for nilotinib or dasatinib. Patients were followed for up to 6 months from the index date to the earliest of the termination of health care plan enrollment, or end of data availability. Treatment adherence was measured by the proportion of days covered (PDC) and compared using generalized linear models. PDC was calculated as the sum of the days of supply for nilotinib or dasatinib, divided by the number of calendar days in the study period (i.e., up to 6 months after the index date). Unadjusted average PDCs were compared between nilotinib and dasatinib users using Wilcoxon sum-rank tests. Multivariate regressions were controlled for age, gender, CML disease complexity, any adverse event at baseline, CML year of diagnosis, comorbidities, and bone marrow or stem cell transplant at baseline. Medication possession ratios and discontinuation rates, defined as a treatment gap ≥30 days, were also evaluated. Results: A total of 521 patients receiving a second-line TKI (452 dasatinib and 69 nilotinib) were studied. Patients had a mean age of 57 years, and all other characteristics were similar between the 2 cohorts with the exception that patients in the dasatinib cohort had a longer mean follow-up period compared to those in the nilotinib cohort (161.6 days vs 141.9 days; P = 0.0105). Patients in the dasatinib cohort were less adherent to their therapy compared to nilotinib patients. The PDC (mean ± standard deviation) over the study period was 0.79 ± 0.23 for nilotinib patients and 0.69 ± 0.28 for dasatinib patients. After adjustment, dasatinib patients were estimated to have a 0.096 lower PDC value (approximately 13% lower) compared with nilotinib patients (P = 0.0086). A greater proportion of dasatinib users had a PDC

Beschreibung: Abstract 4270 Introduction This study compared the healthcare resource utilization and costs associated with long-term imatinib treatment adherence versus non-adherence in patients with chronic myelogenous leukemia (CML). Methods Two large administrative claims databases were combined (MarketScan and Ingenix Impact, 01/2002-07/2008) to identify patients diagnosed with CML (ICD-9 code 205.1x). Patients with ≥2 imatinib prescriptions and continuous enrollment ≥6 months prior to and ≥1month following the first observed imatinib prescription filled (i.e., the index date) were selected. Patients were followed for up to 3 years from the index date to the earliest of the termination of healthcare plan enrollment, end of data availability, imatinib treatment discontinuation for ≥90 consecutive days, switch to another drug (i.e., dasatinib or nilotinib), or a CML remission diagnosis (ICD-9 code 205.11). A longitudinal retrospective open-cohort design was used to measure patients' adherence to imatinib repeatedly over time. Imatinib treatment periods were divided into 90-day intervals. Using the medication possession ratio (MPR), treatment intervals were categorized as adherent (MPR≥85%) or non-adherent (MPR