Dasatinib has shown efficacy in treating patients with Philadelphia chromosome-positive (Ph+) acute leukemia, though some patients develop resistance. The authors of a phase 1 study sought to assess the combination of dasatinib and asciminib in this patient population and found that it was “safe” and may address dasatinib-related treatment resistance.

The study was led by Marlise R. Luskin, MD, MSCE, of the Dana-Farber Cancer Institute, and published in Blood.

A total of 24 patients (median age, 64.5 years; range, 33-85 years) with Ph+ acute lymphocytic leukemia (ALL; n=22) and chronic myeloid leukemia in lymphoid blast crisis (n=2) received escalating daily doses of asciminib to determine the maximum-tolerated dose plus dasatinib 140 mg daily and prednisone 60 mg/m² daily.

After 28-day induction, patients continued dasatinib and asciminib indefinitely or until hematopoietic stem cell transplant. The recommended phase 2 dose of asciminib was 80 mg daily. A dose-limiting toxicity at 160 mg daily was asymptomatic grade 3 pancreatic enzyme elevation without symptomatic pancreatitis; no vaso-occlusive events were reported.

Among patients with de novo ALL, the complete hematologic remission rate was 84% at day 28 and 100% at day 84.

At day 84, 100% of patients achieved complete cytogenetic remission, 89% achieved measurable residual disease negativity (<0.01%) by multicolor flow cytometry, 74% achieved BCR::ABL1 RT-PCR <0.1%, and 26% achieved BCR::ABL1 RT-PCR <0.01%.

“Dual BCR::ABL1 inhibition with dasatinib and asciminib is safe with encouraging activity in patients with de novo Ph+ ALL,” the authors concluded.

Reference

Luskin MR, Murakami MA, Keating JH, et al. Asciminib plus dasatinib and prednisone for Philadelphia chromosome-positive acute leukemia. Blood. 2024:blood.2024025800. doi:10.1182/blood.2024025800