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

Abstract

Low‐dose dasatinib is safe and effective in patients with chronic myeloid leukemia in chronic phase (CML‐CP). No randomized trials have compared the outcome with standard‐dose dasatinib. This study aims to compare the outcome of patients with CML‐CP treated with frontline dasatinib 50 versus 100 mg/day. We analyzed 233 patients with newly diagnosed CML‐CP treated with low‐dose dasatinib (N = 83) or standard‐dose dasatinib (N = 150). Propensity score analysis with 1:1 matching was performed and identified 77 patients in each cohort without significant baseline differences. Response rates were reported as the cumulative incidences of complete cytogenetic response, major molecular response (MMR), molecular response (MR)4, and MR4.5. Failure‐free survival (FFS), event‐free survival (EFS), transformation‐free survival (TFS), and overall survival (OS) were also compared. Patients on low‐dose dasatinib with suboptimal response by European LeukemiaNet (ELN) 2013 criteria had the option to increase the dose to 100 mg/day. The overall median follow‐up time was 60 months. The 3‐year MMR rates were 92% and 84% for low‐dose and standard‐dose dasatinib, respectively (p = .23). Dasatinib 50 mg/day induced higher cumulative incidence of MR4 (77% vs. 66%; p = .04) and MR4.5 (77% vs. 62%; p = .02) at 3 years. The 4‐year FFS, EFS and OS rates were 89% versus 77% (p = .04), 95% versus 92% (p = .06), and 97% versus 96% (p = .78) with low‐dose and standard‐dose dasatinib, respectively. The rate of any grade pleural effusion was 5% with dasatinib 50 mg/day compared to 21% with 100 mg/day. Dasatinib 50 mg/day is at least as effective as 100 mg/day with a better safety profile and drug exposure.

Tyrosine kinase inhibitors dosing for chronic phase chronic myeloid leukemia: The case for starting low with dasatinib (50 mg/day) and ponatinib (15 mg/day)

“…Obviously, the presence of ABL1 mutations, such as T315I, dictates a more specific mutation‐targeted approach, our current preference being ponatinib. In the current issue of AJH , Jabbour and colleagues from MD Anderson Cancer Center (MDACC) share their experience in using dasatinib at either 50 or 100 mg/day, for frontline therapy in CML‐CP 19 . The authors used propensity score analysis to compare the two doses among 154 patients (77 for each dose level) selected from a cohort of 233.…”

“…It was also pointed out by the authors that among the 77 patients in the dasatinib 50 mg daily cohort, only 2 (3%) patients required dose escalation to dasatinib 100 mg/day, for suboptimal response ( Koji Sasaki, personal communication 8/17/2022 ). The authors stated that low‐dose dasatinib (50 mg/day) was the standard of care at their institution for newly‐diagnosed CML‐CP 19 . In line with this experience from MDACC, a recent study from Japan reported on 52 TKI‐naïve older CML‐CP patients (median age 78 years, range 74–83) treated with dasatinib at 20 mg/day; at a median follow‐up of 1 year, 60% of the patients achieved MMR at 12 months while grade‐3/4 adverse events were reported in 23%; pleural effusions (all grade‐1/2) were reported in only 8%.…”

“…The authors stated that low-dose dasatinib (50 mg/day) was the standard of care at their institution for newlydiagnosed CML-CP. 19 In line with this experience from MDACC, a recent study from Japan reported on 52 TKI-naïve older CML-CP patients (median age 78 years, range 74-83) treated with dasatinib at 20 mg/day; at a median follow-up of 1 year, 60% of the patients achieved MMR at 12 months while grade-3/4 adverse events were reported in 23%; pleural effusions (all grade-1/2) were reported in only 8%. Taken together, these observations reinforce our own practice of using dasatinib as second-line drug of choice in CML-CP 16 and, in this regard, we welcome the possibility of using a lower dose, at least in those patients who are intolerant, as opposed to resistant, to first-line treatment with imatinib.…”

“…In the current issue of AJH, Jabbour and colleagues from MD Anderson Cancer Center (MDACC) share their experience in using dasatinib at either 50 or 100 mg/day, for frontline therapy in CML-CP. 19 The authors used propensity score analysis to compare the two doses among 154 patients (77 for each dose level) selected from a cohort of 233. At a median follow-up time of 5 years, 3-year MMR rates were similar between the two doses at 92% and 84%, respectively for the low (50 mg/day) and standard (100 mg/day) dose levels; interestingly, DMR (ie, MR4-4.5) rates were significantly higher in the low dose cohort; the 4-year survival rates were also similar at 97% versus 96%.…”

Management of chronic myeloid leukemia in 2023 – common ground and common sense

“…Thus, over the past decade, we have learned that dasatinib 50 mg daily is safer and as effective as 100 mg daily [ 30 , 31 , 81 ]. Bosutinib side-effects can be mitigated with a dose-escalation schedule: 100 mg daily x 1-2 weeks, then 200 mg daily x 2–4 weeks, then 300 mg daily x 1 month, then adjust the dose to 400 mg daily (approved dose in frontline therapy) or a lower or higher dose (500 mg daily; approved in subsequent-line therapies) depending on the response, CML status (frontline or later lines) and side-effects [ 82 , 83 ].…”