Chronic Myeloid Leukemia Coverage from Every Angle

EHA25 Virtual: Dose Reduction of Second-Generation TKIs in CML

By: Sarah Campen, PharmD
Posted: Friday, June 19, 2020

Reducing the dose of second-generation tyrosine kinase inhibitors (TKIs) in patients with chronic myeloid leukemia (CML) who have a major or deep molecular response seems to decrease the risk of drug toxicities and prevent potential adverse events associated with TKI therapy, found a retrospective Russian study presented during the virtual edition of the 25th European Hematology Association (EHA) Annual Congress (EHA25 Virtual; Abstract PB1951). Dose reduction may also be a cost-effective approach to therapy, noted Anna G. Turkina, MD, of the National Research Facility for Hematology, Moscow, and colleagues.

The study included 36 patients with CML who had achieved either major molecular response (19%) or deep molecular response (81%) on a second-generation TKI and were subsequently treated with a reduced dose of that TKI. The median duration of major or deep molecular response was 21.5 months at the time of dose reduction, and the most commonly cited reason for dose reduction was toxicity.

The TKIs in the study included nilotinib (78%) and dasatinib (22%). Initial daily doses of nilotinib ranged from 400 to 800 mg and were reduced to 200 to 600 mg daily; as for patients treated with dasatinib, initial daily doses varied from 100 to 140 mg and were reduced to 50 to 70 mg.

The rate of molecular relapse-free survival at 12 months was 90%, 96%, and 64% in all study patients, the deep molecular response cohort, and the major molecular response cohort, respectively. Loss of major molecular response occurred in three patients at 3, 6, and 8 months after dose reduction; however, major molecular response was achieved in all patients after the standard dose was resumed. Previously observed adverse events were resolved after dose reduction in 90% of patients, and no new or unexpected adverse events were observed after dose reduction.

“At least 1 year of [major molecular response] duration on the standard dose is desirable before dose reduction,” concluded the authors.

Disclosure: The study authors’ disclosure information may be found at

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