Dasatinib Plus Venetoclax Is Safe in Patients with Early Chronic-Phase CML

Dasatinib plus venetoclax is safe and effective in patients with early chronic phase chronic myeloid leukemia compared with dasatinib alone, according to phase II data presented at the 65th American Society of Hematology Annual Meeting & Exposition.

Sixty-five patients, with a median age of 46 years, were enrolled in the clinical trial and treated between April 2018 and August 2021. More than half of the patients were women (57%), 21 (32%) had splenomegaly, 46 (71%) had low Sokal risk disease, and 3 (5%) had high Sokal risk disease. All patients had an ECOG Performance Status of 0 or 1. The dasatinib alone group included 85 patients with comparable characteristics.

The treatment regimen consisted of single-agent dasatinib 50 mg/d for the first three months. Venetoclax was given from four months on for a total of three years. A regimen adjustment was made following the development of neutropenia in some patients who were given a continuous dose of venetoclax 200 mg/day.

Major molecular response (MMR) by 12 months was the primary endpoint. Secondary endpoints included the 12-month rate of MR4.5 and the cumulative overall rate of MR4.5; the rates of MR4.5 at 6-, 12-, 18-, 24-, and 36-months of the combination; the proportion of patients with sustained MR4.5 of three years and more; the treatment-free remission (TFS) rate; overall survival; and safety.

MMR or deeper response was achieved by 12 months in 85% of the patients. The median time to MMR, MR4, and MR4.5 were 6.2 months, 13 months, and 23.9 months from the start of dasatinib, respectively. Furthermore, the two-year failure-free survival was 96% in the combination group versus 92% in the dasatinib alone group.

When comparing the dasatinib/venetoclax combination with dasatinib alone, the 12-month MMR rates were 79% versus 78%, respectively.

Adverse events (AEs) were seen in both groups within a year of therapy. Grade 1/2 neutropenia occurred more often in the combination group (52%) compared with single-agent dasatinib (21%). The incidence of grade 3/4 neutropenia was 17% versus 8%, respectively.

After a median follow-up of just over two years, two patients in the combination group discontinued treatment because of AEs (gastrointestinal intolerance and pleural effusion).

Reference

Haddad FG, Jabbour E, Sasaki K, et al. Phase 2 study of dasatinib with and without venetoclax in patients with early chronic phase chronic myeloid leukemia (ECP-CML). Abstract #870. Presented at 65th American Society of Hematology Annual Meeting & Exposition; December 9-12; San Diego, California.