Dasatinib Discontinuation Safe for Patients With CML and Deep Molecular Response

Among patients with chronic myeloid leukemia (CML) who received dasatinib as first-line treatment for ≥36 months and sustained deep molecular response, therapy could safely be discontinued, according to results from a phase 2 trial published in The Lancet Hematology (2020 Jan 21. Epub ahead of print).

“A previous dasatinib discontinuation…trial showed that 31 (49%) of 63 patients with chronic-phase…[CML] who were treated with second-line or subsequent dasatinib could discontinue the drug safely. However, the safety and efficacy of discontinuing first-line dasatinib remains unclear,” explained Prof Shinya Kimura, MD, Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Saga University, Japan, and colleagues.

This led Dr Kimura and co-investigators to conduct a single-arm, multi-center trial at 23 hospitals across Japan to assess molecular relapse-free survival at 6 months after dasatinib discontinuation.

The trial enrolled patients with newly diagnosed chronic-phase CML who received ≥24 months of dasatinib therapy and who sustained a deep molecular response.

The primary end point was molecular relapse-free survival after dasatinib discontinuation at 6 months and was assessed in all patients who completed the 12-month consolidation phase. Safety was also assessed in all patients who received dasatinib therapy.

A total of 68 patients were enrolled in the trial between September 20, 2013, and July 12, 2016, and assigned to the consolidation phase. Of these patients, 9 were excluded during the consolidation phase and 1 was excluded after study completion.

Ultimately, 58 patients discontinued dasatinib and were assessed for the primary end point. Of these patients, 32 (55%) had treatment-free remission at 6 months after discontinuation, with a median follow-up of 23.3 months. The treatment-free remission rate was 55.2%.

Dr Kimura and colleagues reported that no nonhematologic adverse events (AEs) grade ≥2 occurred prior to dasatinib discontinuation. The most common hematologic AE was anemia (21%), and others included grade 3 neutropenia (4%) and grade 4 lymphopenia (1%).

“Our findings suggest that dasatinib could be safely discontinued after first-line treatment in patients with…[CML] who had received at least 36 months of therapy and sustained deep molecular response; however, further confirmation in larger trials is needed,” the researchers concluded.—Janelle Bradley