New Platelet Response Data: Eltrombopag in CMML With Severe Thrombocytopenia

A clinical trial has been conducted on the use of the thrombopoietin receptor agonist eltrombopag in patients with chronic myelomonocytic leukemia (CMML) with severe thrombocytopenia. Its findings were presented in a letter published in Leukemia.

“Carefully escalated eltrombopag induces frequent but transient platelet responses in CMML patients with thrombocytopenia,” the trial investigators wrote.

This open-label, single-arm, phase II trial enrolled 29 patients across 15 centers who had CMML and lower risk disease, with platelets of less than 50 ×10⁹/L and a maximum of 5% bone marrow blasts. The cohort had a median age of 78 years, and 21 patients were male. It had a median platelet count of 29 ×10⁹/L and 12 patients were dependent on platelet transfusions. Twenty-seven patients had undergone centralized genetics, 93% of whom had TET2 mutation, 52% RUNX1 mutation, 37% SRSF2 mutation, 30% ASXL1 mutation, 17% PHF6 mutation, and 15% EZH2 mutation.

Eleven patients in the cohort had undergone at least one prior therapy, seven of whom had received immune thrombocytopenia-directed drugs in the form of steroids or intravenous immunoglobulins.

For at least 12 weeks, patients received eltrombopag at a starting dose of 100 mg once daily, which was later amended to 50 mg/day. Dose was adjustable up to 300 mg/day and patients receiving benefit could continue the treatment for up to 24 months.

Among the reported efficacy results, 48.3% of the cohort achieved a platelet response at 12 weeks and 72.4% had response at any time on the study. The median duration of response in the cohort was 2.6 months, and 34.5% of the cohort had response which lasted six months or longer. The cohort had an overall survival rate of 47% and a two-year progression-free survival rate of 23%.

Regarding safety findings, Grade 3 hepatobiliary adverse events affected 10% of the cohort.

Reference

Rabian F, Chevret S, Gruson B, et al. Eltrombopag in chronic myelomonocytic leukemia with severe thrombocytopenia. A Groupe Francophone des Myélodysplasies (GFM) study. Leukemia. 2024. doi:10.1038/s41375-024-02402-8