Safety and Efficacy of Dasatinib (DAS) Vs. Imatinib (IM) by Baseline Comorbidity In Patients with Chronic Myeloid Leukemia In Chronic Phase (CML-CP): Analysis of the DASISION Trial.

BCR-ABL kinase inhibitors DAS, nilotinib and IM have become the primary treatment modality for patients (pts) with CML-CP. Pre-treatment comorbid conditions have been proposed to help select a second-line BCR-ABL inhibitor for IM-resistant CML-CP. The DASISION trial is a large Phase 3 trial comparing DAS with IM as initial treatment in pts with newly diagnosed CML-CP and has demonstrated superior efficacy of DAS 100 mg once daily after a minimum follow-up of 12 months (Kantarjian, H, et al. N Engl J Med 2010;362:2260). This analysis assessed the impact of baseline comorbidities on safety and efficacy of these agents when used as initial therapy for CML-CP.

519 pts with newly diagnosed CML-CP were randomized to either DAS 100 mg once daily (n = 259) or IM 400 mg once daily (n = 260). Key exclusion criteria included serious uncontrolled medical disorders or active infections; uncontrolled or serious cardiovascular disease; prior or concurrent malignancy; inadequate hepatic or renal function; and ECOG performance status of ≥ 3. Pts were analyzed according to the number (0, ≥ 1 and ≥ 2) and type of baseline comorbidity (allergic, dermatologic, diabetes, endocrine-metabolic, gastrointestinal, hematologic-lymphatic, hepatobiliary, hyperlipidemia, musculoskeletal, renal and respiratory), and age (< 46, 46–65 and > 65 y). Complete cytogenetic response (CCyR), major molecular response (MMR) and drug-related adverse events (AEs) were analyzed across these groups. Cardiovascular comorbidities were analyzed separately and are not included here.

Across the 2 treatment arms, 74% of the pts had ³1 baseline comorbidity and 47% had ³2. The distribution of comorbidities including allergic (n = 61), dermatologic (n = 62), diabetes (n = 31), endocrine/metabolic (n = 98), gastrointestinal (n = 176), hematologic/lymphatic (n = 57), hepatobiliary (n = 56), hyperlipidemia (n = 41), musculoskeletal (n = 150), neoplasia (n = 17), renal (n = 33) and respiratory (n = 72) was balanced across the 2 arms. Proportions of pts across 3 Hasford risk groups were similar between pts with baseline comorbidity and those without. Safety profiles of DAS and IM in pts with and without baseline comorbidities were comparable (Table). Proportions of pts with at least 1 dose interruption or dose reduction were also similar with or without any comorbidity (Table). Pts with ³2 comorbidities and pt grouped by comorbidity type including diabetes mellitus, hepatobiliary conditions and hyperlipidemia also had generally similar safety profiles. In both arms, the 12-mo rates of CCyR and MMR were similar (Table). In DAS-treated pts with diabetes (n = 18), hepatobiliary conditions (n = 32) and hyperlipidemia (n = 22), CCyR rates were 67, 78 and 96%, respectively; the respective MMR rates were 44, 56 and 59%. IM pts with diabetes (n = 13), hepatobiliary conditions (n = 24) and hyperlipidemia (n = 19) had CCyR rates of 69, 75 and 79%, respectively; and MMR rates of 15, 29 and 32%, respectively. In DAS-treated pts, CCyR rates were 88% for pts aged < 46 y (n = 128), 78% for those aged 46–65 y (n = 111) and 85% for those aged > 65 y (n = 20); the corresponding MMR rates were 45, 47 and 50%, respectively. The corresponding IM age groups (n = 111, 125 and 24, respectively) had CCyR rates of 70, 70 and 83%, respectively; and MMR rates of 26, 30, 29%, respectively. Safety profiles were generally similar across age groups in both treatment arms, except that fluid retention rates in pts aged < 46, 46–65 and > 65 y were 13, 25 and 35%, respectively, for DAS; and 34, 45 and 67%, respectively, for IM.

The presence of baseline comorbidities appeared to have no effect on the safety and efficacy of either DAS or IM as initial therapy for CML-CP.

Cortes:Brostol-Myers Squibb, Novartis and Wyeth: Consultancy, Honoraria. Kantarjian:BMS, Pfizer and Novartis: Research Funding; Novartis: Consultancy. Baccarani:Brostol-Myers Squibb and Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees. Shah:Bristol-Myers Squibb, Novartis and Ariad: Membership on an entity's Board of Directors or advisory committees. Bradley-Garelik:Bristol-Myers Squibb: Employment, Equity Ownership. Dejardin:Bristol-Myers Squibb: Employment, Equity Ownership. Hochhaus:Brostol-Myers Squibb, Novartis: Consultancy, Research Funding.