Long‐term follow‐up of lower dose dasatinib (50 mg daily) as frontline therapy in newly diagnosed chronic‐phase chronic myeloid leukemia

Abstract

Background Dasatinib, a potent Bcr‐Abl tyrosine kinase inhibitor, is approved for the treatment of chronic‐phase chronic myeloid leukemia (CML‐CP) in the frontline and salvage settings. Notable side effects include pleural effusions and myelosuppression. Dasatinib at 50 mg daily has previously been reported to be active and better tolerated than the approved 100‐mg daily dose. The aim of this study was to update the long‐term follow‐up results of dasatinib at 50 mg daily as frontline therapy for CML‐CP. Methods Eighty‐three patients with newly diagnosed CML‐CP received dasatinib at 50 mg daily. Eligibility and response criteria were standards used in previous protocols. Results After a minimum follow‐up of 12 months, 81 patients were evaluable. Two patients came off the study in less than 3 months. The rates of BCR‐ABL1 transcript levels (International Standard) at ≤10% and ≤1% at 3 months were 96% and 77%, respectively. The cumulative rates for a complete cytogenetic response by 6 and 12 months were 77% and 95%, respectively. The cumulative rates for a major molecular response, a molecular response with a 4.0‐log reduction, and a molecular response with a 4.5‐log reduction by 12 months were 81%, 55%, and 49%, respectively. Twenty‐one patients (25%) had treatment interruptions for a median of 13 days (range, 4‐64 days). Five patients (6%) developed pleural effusions; 4 of these patients (80%) required a dose reduction. Two patients (2%) failed to achieve any cytogenetic or molecular response and were taken off the study. At a median follow‐up of 24 months, none of the patients had disease transformation to an accelerated or blastic phase. The 2‐year event‐free and overall survival rates were 100%. Conclusions These updated results continue to support 50 mg of dasatinib daily as an effective and safe dose for early CML‐CP.

European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia

“…An increase of the dose is not recommended. Because of fewer side-effects at similar response rates in CP, a dose as low as 50 mg is an option [51].…”

Chronic Myeloid Leukemia, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology

“…Long-term follow-up results of a single-arm study in a small cohort of patients suggest that dasatinib 50 mg once daily may have similar efficacy. 83 Treatment interruption of dasatinib at 100 mg once daily and reintroduction at a lower dose (40 mg twice daily or 60 mg once daily) has been shown to be effective for patients with intolerance to dasatinib at 100 mg once daily. 84,85 Dasatinib at 50 mg (20 mg with careful monitoring in selected patients) should be considered for patients with clinically significant intolerance to dasatinib 100 mg once daily to avoid serious adverse events necessitating the discontinuation of dasatinib (eg, pleural effusion, myelosuppression).…”

Discontinuation of tyrosine kinase inhibitors in chronic myeloid leukemia: when and for whom?

“…58,59 Both dasatinib and nilotinib have demonstrated efficacy at doses lower than the FDA-approved dose. In a recently published phase II study from the MD Anderson Cancer Center, 60 dasatinib was given at a dose of 50 mg daily, instead of the FDAapproved dose of 100 mg, to newly diagnosed patients. Of the 81 patients enrolled, 81% had achieved a MMR at 12 months according to the follow-up data at the time of the publication.…”