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Objective:To determine treatment regimens used in clinical practice and the associated clinical outcomes among third line (3L) follicular lymphoma (FL) patients in the United States (US).

Background: Novel therapies for multiply relapsed follicular lymphoma (FL) are often evaluated in single arm trials with no comparative data on patients receiving usual care. This study (ReCORD-FL) therefore sought to construct a historical control cohort to augment current and future single arm trials in relapsed/refractory (r/r) FL. The analytic aims were to document patient characteristics, treatment patterns and clinical outcomes in a r/r FL population treated with standard therapies in routine practice.

Background:Follicular lymphoma (FL) is the second most frequently diagnosed Non-Hodgkin lymphoma subtype in Western countries. Patients often undergo multiple lines of therapy over many years throughout the course of their disease with worse survival after each successive line of therapy. Recent findings from the ELARA trial showed that tisagenlecleucel, a chimeric antigen receptor (CAR)-T cell therapy, had durable complete response rate of 66.0%, with a probability of 79% (95% CI, 66%-87%) to remain in response ≥6 months (overall response rate 86.2%) in patients with relapsed or refractory (r/r) FL. Prior evidence in patients with r/r diffuse large B-cell lymphoma demonstrated that tisagenlecleucel can be safely infused in an outpatient setting and may reduce healthcare resource utilization (HCRU) (Lyman et al, 2020). we present the first HCRU among patients with r/r FL who received tisagenlecleucel in the ELARA trial.

Fowler: BostonGene, Corp: Current Employment, Current holder of stock options in a privately-held company; Bristol Myers Squibb, F. Hoffmann-La Roche Ltd, TG Therapeutics and Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding. Dickinson: Gilead Sciences: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria; Bristol-Myers Squibb: Consultancy, Honoraria; Takeda: Research Funding; Celgene: Research Funding; Amgen: Honoraria; Roche: Consultancy, Honoraria, Other: travel, accommodation, expenses, Research Funding, Speakers Bureau; Novartis: Consultancy, Honoraria, Research Funding, Speakers Bureau. Chen: Mesolbast: Honoraria; Morphosys: Honoraria. Andreadis: GenMAB: Research Funding; Epizyme: Honoraria; Atara: Consultancy, Honoraria; Crispr Therapeutics: Research Funding; Novartis: Research Funding; BMS/Celgene: Research Funding; Karyopharm: Honoraria; Incyte: Honoraria; Kite: Honoraria; Merck: Research Funding; Roche: Current equity holder in publicly-traded company, Ended employment in the past 24 months; TG Therapeutics: Honoraria. Tiwari: Novartis Healthcare private limited: Current Employment. Masood: Novartis: Current Employment, Current holder of stock options in a privately-held company. Ramos: Novartis: Current Employment, Current equity holder in publicly-traded company. Bollu: Novartis: Current Employment, Current equity holder in publicly-traded company. Jousseaume: Novartis: Current Employment, Current equity holder in publicly-traded company. Thieblemont: Kyte: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses , Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Gilead Sciences: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Cellectis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses ; Hospira: Research Funding; Bayer: Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Accommodations, Expenses . Dreyling: BeiGene: Consultancy; Astra Zeneca: Consultancy, Speakers Bureau; Janssen: Consultancy, Research Funding, Speakers Bureau; Novartis: Consultancy, Speakers Bureau; Roche: Consultancy, Research Funding, Speakers Bureau; Abbvie: Research Funding; Celgene: Consultancy, Research Funding, Speakers Bureau; Amgen: Speakers Bureau; Genmab: Consultancy; Incyte: Consultancy, Speakers Bureau; Gilead/Kite: Consultancy, Research Funding, Speakers Bureau; Bayer HealthCare Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau. Schuster: Celgene: Consultancy, Honoraria, Research Funding; Nordic Nanovector: Consultancy; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Abbvie: Consultancy, Research Funding; Acerta Pharma/AstraZeneca: Consultancy; Alimera Sciences: Consultancy; BeiGene: Consultancy; Juno Theraputics: Consultancy, Research Funding; Loxo Oncology: Consultancy; Tessa Theraputics: Consultancy; Genentech/Roche: Consultancy, Research Funding; Pharmaclyclics: Research Funding; Adaptive Biotechnologies: Research Funding; Merck: Research Funding; Incyte: Research Funding; TG Theraputics: Research Funding; DTRM: Research Funding.

Dai: Novartis: Current Employment, Current equity holder in publicly-traded company. Heo: Genesis Research: Current Employment, Current equity holder in publicly-traded company. Rava: Genesis Research: Current Employment, Current equity holder in publicly-traded company. Jousseaume: Novartis: Current Employment, Current equity holder in publicly-traded company. Ramos: Novartis: Current Employment, Current equity holder in publicly-traded company. Bollu: Novartis: Current Employment, Current equity holder in publicly-traded company.

Salles: Beigene, BMS/Celgene, Debiopharm, Genentech/Roche, Genmab, Incyte, Ipsen, anssen, Novartis. Kite/Gilead, Loxo, Miltneiy, Rapt, TAKEDA, Velosbio, Allogene: Consultancy; Abbvie, Epizyme, Morphosys, Regeneron: Consultancy, Honoraria; Bayer: Honoraria. Schuster: Abbvie: Consultancy, Research Funding; Acerta Pharma/AstraZeneca: Consultancy; Alimera Sciences: Consultancy; BeiGene: Consultancy; Juno Theraputics: Consultancy, Research Funding; Loxo Oncology: Consultancy; Tessa Theraputics: Consultancy; Genentech/Roche: Consultancy, Research Funding; Merck: Research Funding; Pharmacyclics: Research Funding; Adaptive Biotechnologies: Research Funding; Incyte: Research Funding; TG Theraputics: Research Funding; Novartis: Consultancy, Honoraria, Patents & Royalties, Research Funding; Nordic Nanovector: Consultancy; Celgene: Consultancy, Honoraria, Research Funding. Kuruvilla: Seattle Genetics: Honoraria; Merck: Honoraria; Novartis: Honoraria; Gilead: Honoraria; BMS: Honoraria; Antengene: Honoraria; Amgen: Honoraria; AbbVie: Honoraria; Karyopharm: Honoraria, Other: Data and Safety Monitoring Board; Janssen: Honoraria, Research Funding; Incyte: Honoraria; Medison Ventures: Honoraria; Roche: Honoraria, Research Funding; AstraZeneca: Honoraria, Research Funding; Pfizer: Honoraria; TG Therapeutics: Honoraria. Patten: GILEAD SCIENCES: Honoraria, Research Funding; ROCHE: Research Funding; ASTRA ZENECA: Honoraria; NOVARTIS: Honoraria; JANSSEN: Honoraria; ABBVIE: Honoraria. von Tresckow: Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Other, Research Funding; Pentixafarm: Consultancy, Honoraria; AbbVie: Other: congress and travel support; BMS-Celgene: Consultancy, Honoraria, Other: congress and travel support; AstraZeneca: Honoraria, Other: congress and travel support; Pfizer: Consultancy, Honoraria; Roche: Consultancy, Honoraria; Kite-Gilead: Consultancy, Honoraria; MSD: Consultancy, Honoraria, Other: congress and travel support, Research Funding; Novartis: Consultancy, Honoraria, Other: congress and travel support, Research Funding. Smith: Alexion, AstraZeneca Rare Disease: Other: Study investigator; Celgene, Genetech, AbbVie: Consultancy. Davis: Novartis, Vertex Pharmaceuticals, Pfizer, Eisai, Eli Lilly, AstraZeneca: Research Funding. Nagar: Novartis, AstraZeneca, Eisai: Research Funding. Zhang: Novartis: Current Employment, Current equity holder in publicly-traded company. Bollu: Novartis: Current Employment, Current equity holder in publicly-traded company. Jousseaume: Novartis: Current Employment, Current equity holder in publicly-traded company. Ramos: Novartis: Current Employment, Current equity holder in publicly-traded company. Wang: Eli Lilly: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding; TG Therapeutics: Membership on an entity's Board of Directors or advisory committees; MorphoSys: Research Funding; Incyte: Membership on an entity's Board of Directors or advisory committees, Research Funding; InnoCare: Research Funding; LOXO Oncology: Membership on an entity's Board of Directors or advisory committees, Research Funding; Genentech: Research Funding. Link: Genentech/Roche: Consultancy, Research Funding; MEI: Consultancy; Novartis, Jannsen: Research Funding.

Abstract 2754

According to the NCCN guidelines, the recommended treatment option for patients diagnosed with Philadelphia-positive (Ph+) chronic myeloid leukemia (CML) in chronic or accelerated phases who are resistant or develop intolerance to first-line imatinib is to switch to one of the two second-generation BCR-ABL tyrosine kinase inhibitors, nilotinib or dasatinib. There is limited information on their comparative adherence. Analysis of adherence may reveal whether these two drugs are being used as intended and how adherence issues may potentially affect clinical outcomes. Nonadherence to imatinib has been associated with loss of cytogenetic response, imatinib failure, and higher rates of inpatient visits. A prior study covering the period up to 6/2009 has revealed a better adherence profile for nilotinib versus dasatinib. Since dasatinib was approved for once daily use in addition to twice daily use in 05/2009, this study replicated the analysis using more recent data to compare adherence between nilotinib and dasatinib as second-line therapies in CML.Medical and pharmacy records from two databases from January 1997 to April 2010 were combined to identify adult patients diagnosed with CML (ICD-9 code 205.1x) with ≥1 prescription for either nilotinib or dasatinib. Patients were required to have continuous enrollment ≥1 month prior to and after the index date, defined as the first prescription for nilotinib or dasatinib, and to continue their treatment ≥1 month before discontinuing or switching to another TKI. Adherence over an up-to 180-day period was evaluated based on the proportion of days covered (PDC; sum of days of medication on hand for nilotinib or dasatinib divided by the number of calendar days in the study period). Medication possession ratio (MPR) was also evaluated in a sensitivity analysis. PDC and MPR were compared between cohorts using linear regression models. Discontinuation was defined as a treatment gap ≥30 days, and rates were compared between cohorts using Kaplan-Meier survival analyses and Cox proportional hazard regression models. In a sensitivity analysis, discontinuation was defined as a treatment gap ≥90 days. All multivariate regression models were controlled for age, gender, CML complexity, adverse events at baseline, number of inpatient days, emergency room (ER) visits and outpatient visits during baseline, medical costs during baseline, CML year of diagnosis, Charlson Comorbidity Index, and bone marrow or stem cell transplant before the index date.Adherence and discontinuation were analyzed for a total of 558 CML patients receiving a second-line TKI (473 dasatinib and 85 nilotinib). Patient characteristics were generally similar. Patients in the dasatinib cohort had a longer mean follow-up period compared with those in the nilotinib cohort (162 days vs. 146 days; P = 0.0007) and greater utilization and costs associated with inpatient and ER services. The mean PDC over the study period for nilotinib was higher compared with dasatinib (0.81 vs 0.68). After adjusting for confounding factors, the nilotinib group had a 0.115 higher PDC (approximately 17% higher) compared to the dasatinib group (P = 0.0004). Additionally, patients in the nilotinib group had a significantly higher MPR compared to patients in the dasatinib group (0.90 vs. 0.77 P = 0.0043). Discontinuation rates (gap ≥30 days) were significantly higher for dasatinib users than for nilotinib users, with an adjusted hazard ratio of 2.15 (P = 0.0013). Dasatinib-treated patients had higher discontinuation rates than nilotinib-treated patients after 3 months (40% vs 22%) and 6 months (50% vs 28%). These unadjusted differences were robust in the sensitivity analysis with discontinuation defined as a treatment gap ≥90 days, but the difference between the cohorts was no longer significant after adjusting for confounding factors (HR 1.76, P = 0.1328).This retrospective study showed that CML patients treated with nilotinib for second-line treatment were significantly more adherent to therapy, based on PDC and MPR, and had a lower discontinuation rate than did patients receiving dasatinib in this analysis. Further studies are needed to better understand treatment-specific factors affecting adherence and persistence (e.g., treatment cost, tolerability profile, dosing convenience).Guerin: Novartis Pharmaceutical Corporation: Annie Guerin is an employee of Analysis Group, Inc, which has received research funds from Novartis Pharmaceuticals. Bollu:Novartis Pharmaceutical Corporation: Employment, Vamsi K. Bollu worked for the Novartis Pharmaceuticals Corporation while performing this analysis but is currently employed by Sunovion Pharmaceuticals Inc. Sunovion Pharmaceuticals Inc. was not in any way associated with this study. Guo:Novartis Pharmaceutical Corporation: Employment. Stepner:Novartis Pharmaceutical Corporation: Michael Stepner is an employee of Analysis Group, Inc, which has received research funds from Novartis Pharmaceuticals. Griffin:Novartis Pharmaceutical Corporation: James D. Griffin is an employee of the Dana Farber Institute which has received consultancy fees from Analysis Group, Inc, which has received research funds from Novartis Pharmaceuticals Corporation. Wu:Novartis Pharmaceutical Corporation: Eric Q. Wu is an employee of Analysis Group, Inc, which has received consultancy funds from Novartis Pharmaceutical Corporation.

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.To compare healthcare resource utilization and costs between CML patients treated with a TKI who developed PE and their matched PE-free controls.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.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<.01), almost 3 times as many IP admissions (IRR=2.96; p<0.01), almost twice as many OP visits (IRR=1.98; p<.01) and ER visits (IRR=1.77; p<.01). Especially, PE patients had almost 10 times as many CML-related IP days (IRR=9.91; p<.01), more than 3 times as many CML-related IP admissions (IRR=3.95; p<0.01), twice as many CML-related OP visits (IRR=2.16; p<.01), and almost 6 times as many CML-related ER visits (IRR=5.60; p<.01). On average, PE-related medical costs were estimated at $11,015 per patient, where 84.2% was accounted for by IP costs. Total costs for all-cause related medical services were estimated at $37,566 for PE patients and $14,841 for PE-free patients. After adjusting for confounding factors, the incremental total medical cost of PE patients was $22,299 (p<.01), mostly due to the incremental OP cost ($12,931; p<.01) and IP cost ($8,737; p<.01). Similarly, PE patients incurred higher CML-related medical costs compared to PE-free patients, with a $15,859 (p<.01) incremental cost.Compared to PE-free patients, PE patients have a substantial economic burden with higher PE-related costs, CML-related costs, and total medical cost.Wu: Analysis Group, Inc.: Employment. Guerin:Analysis Group, Inc.: Employment. Bollu:Novartis: Employment, Equity Ownership. Williams:Novartis: Employment, Equity Ownership. Guo:Novartis Pharmaceuticals Corporation: Employment, Equity Ownership. Ponce de Leon Barido:Analysis Group, Inc.: Employment. Yu:Analysis Group, Inc.: Employment.

Beaumont: Novartis: Research Funding. Coombs:Novartis: Employment, Equity Ownership. Bollu:Novartis: Employment, Equity Ownership. Woodman:Novartis Oncology: Employment. Cella:Novartis: Research Funding.

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.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.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.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.Yu: Analysis Group, Inc.: Employment. Guerin:Analysis Group, Inc.: Employment. Bollu:Novartis: Employment. Cloutier:Analysis Group, Inc.: Employment. Williams:Novartis: Employment, Equity Ownership.

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.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.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 <0.8 and PDC <0.9 (Figure). A statistically significant difference in medication possession ratios at 180 days was also observed; 0.75 ± 0.33 for dasatinib and 0.85 ± 0.27 for nilotinib (P = 0.029). Discontinuation rates were similar between the two drugs with an adjusted hazard ratio (HR) of 1.03 (HR >1 indicates that dasatinib users have a greater discontinuation rate than nilotinib users; 95% confidence interval, 0.63–1.69; P = 0.8981).CML patients treated with second-line nilotinib had significantly better adherence during the 6-month study period than patients treated with second-line dasatinib as defined by the PDC. The medication possession ratio was also greater for nilotinib-treated than dasatinib-treated patients; however, discontinuation rates were similar between the two treatment groups. Although adherence may be related to a greater safety profile as adverse events may disrupt treatment, head-to-head comparisons of the drugs as second-line therapy for CML have not been performed. Further research is necessary to understand and define all factors, including safety, involved in affecting treatment adherence for nilotinib and dasatinib patients.Guerin: Analysis Group, Inc.: Employment. Bollu:Novartis: Employment. Guo:Novartis: Employment. Griffin:Novartis: Consultancy, Research Funding. Yu:Analysis Group, Inc.: Employment. Wu:Analysis Group, Inc.: Employment.

Abstract 4758

Abstract 3437

Abstract 3841

Abstract 3826

Imatinib mesylate (IM), an oral tyrosine kinase inhibitor, is now standard front line therapy for the treatment of patients with chronic myeloid leukemia (CML). As demonstrated in the IRIS trial, IM has a 7-year over-all survival rate of 86%. While treatment with IM is effective, adherence among patients receiving IM is suboptimal.A retrospective cohort study was performed using Medstat Marketscan employer-based data from Jan 1, 2004 through October 1, 2008 for the purposes of identifying key factors associated with patients who are non-adherent to IM. Patients included in the study were adult patients below age 65, with a diagnosis of CML (ICD-9 205.1x), received two or more prescriptions for IM treatment, and are continuously eligible in the health plan. Patients were required to have a 12-month follow-up data of their complete medical and pharmacy events from their first IM prescription in the study period. Independent variables examined included patient demographics, CML disease complexity, frequency of medical treatment received for adverse events, plan type (PPO/HMO), duration of time on IM, duration of time between CML diagnosis and initiation of IM, average daily dose of starting IM, use of chemotherapies prior to initiation of IM, comorbid conditions, bone marrow/stem cell treatment, and the average percent of patient copayment. Patient adherence to IM treatment was measured by calculating average medication possession ratio (MPR) over the 12-month period. Patients were categorized as adhering to the treatment if they maintained on average an MPR of >85%. A sensitivity analysis was performed utilizing an MPR cut-off of 80%. Descriptive and multivariate statistics were conducted. Logistic regression models were developed to determine the factors that influenced odds of achieving an 80% and 85%, adherence rates.A total of 522 patients had a CML diagnosis and received two or more prescriptions of IM treatment. After applying the exclusion criteria, the final sample included data from 430 patients. The mean age of the patients was 49 years and majority were male (54%). Only 15% of patients received additional chemotherapy during the study period. The number of unique medications consumed by patients averaged 14. The mean MPR in this patient group was 80%, with only 60% of patients categorized as adherent based on MPR of >85%. The following factors were found to be significantly associated with patients who had an MPR of '85%: lower age (p<0.05), shorter exposure to IM (p<0.001), starting IM dose of ≤400 mg (p<0.005), longer time lag between CML diagnosis to IM prescription fill (p<0.0005), higher concomitant prescriptions (p<0.05), and higher percentage of copayment (p<0.01).Approximately 40% of patients receiving IM treatment were categorized as non-adherent to the treatment. Understanding the factors associated with failure to adhere to the treatment regimen will help physicians assess and educate patients receiving CML treatment. Our findings suggest that duration on IM treatment, time lag between CML diagnosis and IM index date, starting IM dose, and patient cost-sharing to be strong predictors of IM non-adherence, suggesting a need for monitoring of these areas within patients with CML. Persistent monitoring, ongoing dialogue, and appropriate IM dosing is crucial to achieving optimal patient adherence in patients with CML.StCharles: Novartis Pharmaceuticals Corporation: Research Funding. Bollu:Novartis Pharmaceuticals Corporation: Employment. Hornyak:Novartis Pharmaceuticals Corporation: Employment. Coombs:Novartis Pharmaceuticals Corporation: Employment. Blanchette:Novartis Pharmaceuticals Corporation: Research Funding. DeAngelo:Enzon Pharmaceuticals: Research Funding; Celgene: Speakers Bureau; Bristol-Meyers Squibb: Speakers Bureau; Novartis: Speakers Bureau.

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).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<85%). Patients' healthcare utilization and costs were compared between adherent and non-adherent intervals. Multivariate regression models were used to compare rates of inpatient admissions, outpatient visits, emergency room visits, and total urgent care visits. Regression models controlled for age, gender, CML complexity, treatment duration, prior chemotherapies, prior adverse events, Charlson comorbidity index, and prior resource utilization. Additional regression models including past cumulative MPR were used to assess the long term impact of non-adherence.For the 1,877 CML patients who met the selection criteria, there were 6,175 adherent and 3,163 non-adherent intervals. Only 34% of patients were completely adherent throughout their observation period. During non-adherent intervals, patients incurred significantly more frequent total urgent care visits (IRR=1.82, p<.001), including inpatient visits (IRR=2.76, p<.001) and emergency room visits (IRR=1.25, p=.021), and more frequent outpatient visits (IRR=1.09 p=.001) compared to adherent intervals. Though non-adherence was associated with lower pharmacy cost by $3,053 (p<.001) over 90 days, this difference was outweighed by a $4,531 higher medical cost (p<.001), resulting in a net cost increase of $1,477 (p<.001) over adherent intervals. Patients who were adherent throughout their observation period incurred an average cost of $11,759 per quarter, compared to $13,773 for patients who were not always adherent. When extrapolated to the 3-year study, health care costs were $24,168 less per patient for patients who were adherent at each of the studied quarters. In models where both the current adherence status and the long-term cumulative impact of past adherence was taken into account, for patients who had always been adherent (past cumulative MPR≥85%), total cost was $883 (p=.084) higher in a non-adherent interval (current MPR<85%) compared to an adherent interval (current MPR≥85%). In patients who had not always been adherent (past cumulative MPR<85%) an adherent interval cost (current MPR≥85%) $1,239 (p=.002) more, while another non-adherent interval (current MPR<85%) cost $2,122 (p<.001) more compared to an adherent interval in patients who had always been adherent (both current and past cumulative MPR≥85%).Our analysis indicates that imatinib non-adherence is associated with significant negative economic consequences, while continuous adherence to imatinib in CML patients was associated with lower healthcare resource utilization and costs.Wu: Novartis: Consultancy, I am working for Analysis Group Inc and Analysis Group Inc received funds from Novartis to conduct the analysis. Bollu:Novartis Oncology: Employment. Guo:Novartis Pharmaceuticals Corporation: Employment. Guerin:Novartis: Consultancy, I am working for Analysis Group Inc and Analysis Group Inc received funds from Novartis to conduct the analysis. Yu:Novartis: Consultancy, I am working for Analysis Group Inc and Analysis Group Inc received funds from Novartis to conduct the analysis. Sirulnik:Novartis Pharmaceutical Corporation: Employment. Griffin:Novartis Pharmaceutical Corporation: Consultancy, I have.

Dasatinib and nilotinib are both indicated to treat chronic myeloid leukemia (CML) patients resistant or intolerant to imatinib. This study compared retrospectively the healthcare resource utilization and costs associated with dasatinib versus nilotinib treatment as second line therapies in CML patients.Two large administrative claims databases were combined (MarketScan and Ingenix Impact, 01/2002-12/2008) to identify patients diagnosed with CML (ICD-9 code 205.1x) and treated with a tyrosine kinase inhibitor (TKI) second line therapy. Patients with at least 1 prescription of dasatinib or nilotinib and no prior use of TKI other than imatinib were selected to form the dasatinib second line therapy group and nilotinib second line therapy group, respectively. The index date was defined as the first prescription for dasatinib or nilotinib. Only patients with an index date on or after the date of nilotinib FDA approval (10/27/2007) and continuously enrolled at least 1 month prior to and 1 month after the index date were included. Patients were followed for up to 6 months from the index date to the earliest of the termination of healthcare plan enrollment, or end of data availability. Patient total medical visits, as well as outpatient visits and hospitalization days, were compared between the two groups using incidence rate ratios (IRR). Multivariate negative binomial regression models were applied to estimate IRR while adjusting for baseline differences of the two groups. Patient total costs, pharmacy costs, and medical service costs (including costs associated with outpatient visits, inpatient admissions, emergency room visits, and other medical services) were compared between the nilotinib and dasatinib group. Unadjusted and adjusted cost differences were estimated for each cost component using generalized linear models (GLM) or two-part models. Multivariate regression models to compare patient utilization and costs controlled for potential differences in age, gender, and cancer complexity (Darkow 2007) between the two groups. Costs were adjusted for inflation to 2008 U.S. dollars.A total of 230 CML patients treated with a second line TKI met the selection criteria; 186 patients treated with dasatinib and 44 patients treated with nilotinib were identified. Average age was similar between the two groups: 56.9 ± 16.3 in dasatinib patients and 54.1 ± 12.4 in nilotinib patients (p=.366) and the ratio of females was not statistically different: 44.1% v 56.8% (p=.128). Comorbidity burden, measured by the Charlson comorbidity index, was also similar between the two groups: 3.12 ± 1.90 for dasatinib patients vs. 3.07 ± 1.95 for nilotinib patients (p=.638), as was the proportion of patients with moderate and severe CML complexity: 53.8% vs 61.4% (p=.362) and 27.4% vs 22.7% (p=.526) for dasatinib and nilotinib treated patients, respectively. Mean duration of prior imatinib treatment for both groups was not statistically significant (p=0.189), 662.1 days vs 583.8 days, for nilotinib Vs dasatinib, respectively. Over the follow-up period, dasatinib patients had significantly more medical visits (IRR=1.32, p=.028), as well as outpatient visits (IRR=1.31, p=.033). Dasatinib patients also had 36% more hospital days but the difference was not statistically significant (IRR=1.36, p=0.664). Over the 6 months following the initiation of the second line therapy, compared to patients on nilotinib, patients on dasatinib incurred $18,328 (p<.001) more in total medical services and $6,367 (p=0.04) less in pharmacy costs, resulting in a higher net total healthcare cost of $12,039 (p=.035). The difference in medical costs was mainly explained by the difference of inpatient costs ($12,480 higher for dasatinib patients; p=<.001) and outpatient costs ($5,035 higher for dasatinib patients; p=.001).This preliminary analysis of total cost of treatment data showed that among CML patients treated with a second line TKIs, those treated with dasatinib were associated with higher total healthcare costs and more frequent health care resource utilization than patients treated with nilotinib. Results may be updated when more data on nilotinib patients becomes available.Wu: Novartis: Consultancy, I am working for Analysis Group Inc and Analysis Group Inc received funds from Novartis to conduct the analysis. Bollu:Novartis Oncology: Employment. Guo:Novartis Pharmaceuticals Corporation: Employment. Guerin:Novartis: Consultancy, I am working for Analysis Group Inc and Analysis Group Inc received funds from Novartis to conduct the analysis. Tsaneva:Novartis: Consultancy, I am working for Analysis Group Inc and Analysis Group Inc received funds from Novartis to conduct the analysis. Williams:Novartis Pharmaceutical Corporation: Employment. Griffin:Novartis Pharmaceutical Corporation: Consultancy, I have.

Only few studies have characterized the healthcare burden associated with managing adverse events (AEs) in the second-line treatment of CML. Information on incidence of AEs and resource utilization in managing these events would be valuable treatment related attributes. Nilotinib is a potent and selective BCR-ABL kinase inhibitor that is approved for the treatment of Ph+ CML patients in Chronic Phase (CP) and Accelerated Phase (AP), who were intolerant or have failed previous imatinib treatment. Dasatinib is another approved second-line agent in the treatment of imatinib resistant or intolerant CML. Nilotinib and dasatinib have shown differences in their safety profiles in clinical trials.This study compared the safety profile of nilotinib, observed in a large study of CML patients in a clinical practice setting from participating North American sites to product information of nilotinib and dasatinib, and also compare potential cost differences between the two settings.Adult patients with imatinib resistant or intolerant Ph+ CML in CP, AP, and blast crisis (BC) were recruited to participate in this phase IIIb, open label, multi-center ENACT (Expanding Nilotinib Access in Clinical Trials) study. Data obtained from the participating North America sites is presented here. Patients who previously failed dasatinib treatment were also allowed to participate. The primary objective of the ENACT study was to obtain additional safety information with nilotinib treatment in a clinical practice setting. Patients received nilotinib 400 mg twice daily (BID). Patients were not permitted to dose escalate. A comprehensive set of hematological and non-hematological adverse event information was obtained in the study. Follow-up treatment in managing the AE, either as dose reduction, dose interruption, or other treatment is also recorded. Incidence of adverse events reported in this study was compared to nilotinib and dasatinib product information. Healthcare resource utilization was estimated from a US health plan perspective by constructing six-month marginal cost increase in patients who received follow-up care for the management of adverse event. Cost data were obtained from MedStat market scan database that contained over 5,000 CML patients. Multivariate regression models and sensitivity analyses were conducted to derive the marginal cost estimates.A total of 207 patients (172 CP pts, 15 AP pts, and 20 BC pts) were enrolled in the study from several sites in North America between Jan 2006 – Oct 2008. The median age was 54 years. At study completion, 48% were continuing on study treatment, 25% discontinued treatment due to unsatisfactory therapeutic effect, 14% discontinued due to AEs, and 13% discontinued due to other reasons. Percentage of patients with grade 3/4 hematological AEs suspected of being study drug related in CP, AP were: thrombocytopenia (12%, 20%), neutropenia (9%, 27%) and anemia (1.2%, 13%). The most frequent non hematologic AEs (all grades) included rash, headache, nausea, and fatigue. Study patients requiring additional therapy for the reported hematological adverse events was less than 50% in most cases. Dose reductions and dose interruptions of greater than 5 days to manage AEs occurred in 2.3% and 32% patients, respectively, with median duration of dose interruption of 12 days in CP patients and 7 days in AP patients. Total medical costs associated with managing the adverse events, estimated from MedStat cost data, for both hematological and non-hematological AEs observed in this analysis based on patients receiving additional treatment were $6,314 for CML patients in CP and AP, over a six-month treatment period. Medical costs associated with managing hematological adverse events made up the majority of these costs. The estimated costs from this study were significantly lower compared to the estimated burden of the AEs in the product information for nilotinib or dasatinib ($9,730 and $12,372, respectively).Nilotinib related adverse event costs observed in this large clinical practice setting study compare favorably to the estimated costs from product information from nilotinib and dasatinib. The analysis is comprehensive in estimating the healthcare costs by characterizing the incidence of the AEs, and managing of the AEs through dose reductions, dose interruption or follow-up care.Guerin: Novartis: Consultancy, I am working for Analysis Group Inc and Analysis Group Inc received funds from Novartis to conduct the analysis. Bollu:Novartis Oncology: Employment. Williams:Novartis Pharmaceuticals: Employment.

Abstract 4286

Abstract 4270

Abstract 4285

Abstract 2209