Low-Dose Dasatinib 50 Mg/Day Versus Standard-Dose Dasatinib 100 Mg/Day As Frontline Therapy in Chronic Myeloid Leukemia in Chronic Phase: A Propensity Score Analysis

• Published in: Blood 2021-11, Vol.138 (Supplement 1), p.631-631
• Main Authors: Sasaki, Koji, Jabbour, Elias J., Issa, Ghayas C., Naqvi, Kiran, Skinner, Jeffrey, Anderson, Kristin, Dellasala, Sara E, Yilmaz, Musa, Ferrajoli, Alessandra, Bose, Prithviraj, Thompson, Philip A., Alvarado, Yesid, Jain, Nitin, Garcia-Manero, Guillermo, Takahashi, Koichi, Burger, Jan A., Borthakur, Gautam, Pemmaraju, Naveen, Haddad, Fadi, Khouri, Maria R, Paul, Shilpa, Pierce, Sherry A., Cortes, Jorge E., Kantarjian, Hagop
• Format: Article
• Language: English
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2021-152614

Background: Low-dose dasatinib was shown to be safe and effective in patients with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP). There is no randomized clinical trials to compare the outcome with the standard-dose dasatinib. The aim of this study is to compare responses and outcome of patients with newly diagnosed CML-CP treated with frontline dasatinib 50 mg/day with those who received standard-dose dasatinib 100 mg/day. Method: We analyzed 233 patients with newly diagnosed CML-CP who were treated with low-dose dasatinib 50 mg/day (N=83) or standard-dose dasatinib 100 mg/day (N=150). Responses criteria were previously defined. Failure-free survival (FFS) was calculated from the start date of therapy to the dates of treatment discontinuation for any reason except of treatment-free remission; event-free survival (EFS), to the date of any of the events while on study as defined in the IRIS study; transformation-free survival (TFS), to the date of transformation to accelerated or blast phases during study; overall survival (OS), to the date of death from any cause at any time or date of last follow-up. Patients on low-dose dasatinib who had suboptimal response by European LeukemiaNet criteria had an option to increase the dose to 100 mg/day. Propensity score analysis with 1:1 matching was performed with the nearest neighbor matching method using calipers of width equal to 0.2. Multiple imputation was performed to minimize the bias. Propensity scores were calculated with logistic regression from baseline covariates including age, spleen size by examination, white blood cell count, hemoglobin, platelet count, percentage of basophils, percentage of blasts in peripheral blood and bone marrow, the presence of clonal evolution, and Sokal risk classification to minimize difference. Results: Propensity score matching identified 77 patients in each cohort without significant baseline difference (Table 1). The overall median follow-up was 60 months: 48 months and 131 months for low-dose and standard-dose, respectively. The 12-month major molecular response (MMR) rates were 82% and 75% for low-dose and standard-dose groups, respectively (P=0.229). The cumulative incidence of molecular response (MR)4, MR4.5, and complete molecular response (CMR) rates within 1 year were higher in the low-dose dasatinib group compared with the standard-dose group (63% and 43%, 53% and 36%, and 46% and 33% for each)(P=0.009; P=0.031; P=0.060). The incidence of pleural