Eltrombopag in Chronic Myelomonocytic Leukemia with Severe Thrombocytopenia. A Groupe Francophone Des Myélodysplasies (GFM) Study

Abstract We conducted a multicenter single-arm phase II trial evaluating the oral thrombopoietin receptor agonist eltrombopag in chronic myelomonocytic leukemia (CMML) patients without blast excess and with platelets < 50 x109/L. CMML patients naïve of hypomethylating agents, with bone marrow blasts ≤ 5%, platelets < 50 x109/L and with lower-risk disease received eltrombopag for at least 12 weeks including an 8-week titration. The primary endpoint was platelet response at 12 weeks (IWG 2006 criteria). Twenty-nine patients were enrolled (median age 78 years). Median platelet count was 29 x109/L. CPSS risk was low or intermediate-1 in 55% and 31% of patients respectively. RUNX1 was mutated in 56% of patients. Eight patients dropped out the trial before 12 weeks (including 3 for early progression). A platelet response was achieved in 14 (48.3%, 95% CI 29.4–67.5) patients at 12 weeks, and in 21 (72.4%) at any time on study. Median response duration was 2.6 months, with 10 (34.5%) patients experiencing responses lasting ≥ 6 months. Grade 3 hepatobiliary adverse events occurred in 3 (10%) patients. Two-year progression-free and overall survival were 23% and 47%, respectively. Carefully escalated eltrombopag induces frequent but transient platelet responses in CMML patients with thrombocytopenia.