Real-World Effectiveness of Dasatinib Versus Imatinib in Newly Diagnosed Patients With Chronic Myeloid Leukemia.

INTRODUCTION: Limited data exist comparing dasatinib with imatinib in clinical practice. This study assessed real-world outcomes associated with first-line (1L) dasatinib or imatinib treatment of chronic myeloid leukemia (CML). PATIENTS AND METHODS: This retrospective, observational, United States multisite cohort study analyzed electronic medical record data from adults with Philadelphia chromosome-positive (Ph+) CML in the chronic phase (CML-CP) after 1L dasatinib or imatinib between January 2014 and September 2018. Rates of and times to major molecular response (MMR) and deep molecular response (DMR) were assessed overall and in subgroups (low vs. intermediate/high risk, aged <65 vs. ≥65 years, low/normal vs. high body mass index [BMI]). RESULTS: The dasatinib cohort (n = 309) experienced higher rates of MMR (n = 304, 79% vs. 65%, P < .001) and DMR (44% vs. 25%, P < .001) vs. the imatinib cohort with shorter median times to MMR (11.9 vs. 14.7 months, P < .001) and DMR (30.3 vs. 66.1 months, P < .001). Patients with intermediate-/high-risk disease and those aged <65 years had higher MMR and DMR rates and achieved response earlier with dasatinib (P < .01). Patients with low-risk disease treated with dasatinib had higher rates of DMR (60% vs. 32%, P = .01). Across BMI strata, rates of MMR and DMR were higher with dasatinib (P < .05). CONCLUSIONS: Patients with CML-CP treated with 1L dasatinib achieved higher rates of, with shorter times to, MMR and DMR versus 1L imatinib. These clinically meaningful improvements were observed across subgroups.

An Analysis of Dasatinib Treatment Patterns in Patients with Chronic Myeloid Leukemia after Experiencing Pleural Effusion during Dasatinib Therapy.

INTRODUCTION: Treatment with dasatinib for chronic myeloid leukemia (CML) has been associated with development of pleural effusion; however, data regarding its optimal management are limited. We examined treatment patterns and healthcare resource utilization (HCRU) and costs among patients with CML treated with dasatinib who experienced a subsequent pleural effusion. METHODS: Adults with CML and ≥1 pharmacy claim for dasatinib in 2015-2018 who experienced pleural effusion after dasatinib were identified using data from claims databases. RESULTS: Overall, 123 patients were eligible. After 1 year, of the 38.2% of patients with a dose modification, 72.3% did not switch treatment; among these patients, 70.6% continued treatment. Among patients with a stable dose after pleural effusion (61.8%), 57.9% later switched to another TKI. The mean (SD) duration of dasatinib treatment after pleural effusion was 262.0 (124.0) days for patients with a dose modification versus 149.1 (155.2) days for those with a stable dose (p < 0.001). HCRU and costs were similar between groups. CONCLUSION: Dasatinib dose modification after pleural effusion was not always required; however, patients with dose modifications continued therapy for a longer duration with a lower rate of switching to another TKI versus patients who remained on a stable dose.

Realized and Projected Cost-Savings from the Introduction of Generic Imatinib Through Formulary Management in Patients with Chronic Myelogenous Leukemia.

BACKGROUND: Imatinib, a first-generation tyrosine kinase inhibitor (TKI), and the newer second-generation TKIs have dramatically improved outcomes for patients with chronic myelogenous leukemia (CML). A previous model estimated the potential cost-savings over the next 2 years after the loss of patent exclusivity for imatinib in the United States in 2016 and its availability in a generic form. Payers have indeed realized meaningful savings, but it took 2 years for the prices of generic imatinib to decline substantially. OBJECTIVE: To quantify the cost-savings for a US health plan from the passive substitution of generic imatinib and the impact of step-edit therapy with the use of generic imatinib before coverage of a second-generation TKI. METHODS: We updated the previously published model utilizing hypothetical 1-million-member commercial and Medicare plans to include current TKI use and pricing combined with recent epidemiologic data. Regression models were used to project utilization to 5 years after the loss of imatinib's patent exclusivity. We compared generic imatinib costs with a scenario in which generic imatinib was not available. The impact of a step-edit therapy restriction was explored for patients with incident CML. The analyses were repeated for the entire US population based on national census data. RESULTS: The 1-million-member commercial plan saved $0.5 million (3%) from pharmacy spending on TKIs in year 1 and $3.9 million (19%) in year 2 after the loss of patent exclusivity. The projected savings significantly increased to $7.8 million (37%), $8.3 million (39%), and $8.6 million (40%) in years 3, 4, and 5, respectively. Step-edits strategies were projected to result in small incremental savings of $0.3 million (1.5%) annually in years 3 to 5. The 1-million-member Medicare plan saved $1.7 million (3%) in year 1 and $14.1 million (19%) in year 2. The projected savings were $27.8 million (37%), $29.5 million (39%), and $30.8 million (40%), with step-edit estimated to add only $0.9 million (1.2%) annually in years 3 to 5. Generic imatinib saved US payers $2.5 billion (13% of the total spending on TKIs) in years 1 and 2. In years 3 to 5, the cumulative projected savings totaled $12.2 billion, and the savings were expected to grow to 39% as a result of passive generic imatinib substitution, with only 1.7% additional savings from step-edit restriction. CONCLUSIONS: As a result of a lower price for generic imatinib relative to the brand-name version of the drug, substantial cost-savings to US payers over the next 3 years are expected without step-edit formulary management restrictions. Cost-saving strategies, including formulary management restrictions, should adhere to evidence-based guidelines to ensure the appropriate use of generic imatinib and all available TKIs, with the objective to maintain positive outcomes and, in turn, increase the value of patient care.