The effect of eltrombopag in managing thrombocytopenia associated with tyrosine kinase therapy in patients with chronic myeloid leukemia and myelofibrosis.

e18539 Background: Tyrosine kinase inhibitors (TKIs) are standard therapy for chronic phase (CP) chronic myeloid leukemia (CML). Up to have patients with CML may develop grade ≥3 thrombocytopenia, leading to treatment interruptions and dose reductions. Similarly, management of thrombocytopenia in myelofibrosis (MF) can be challenging because the condition may result in dose adjustments and interruptions of ruxolitinib. Methods: We conducted a non-randomized, phase II, single-arm study to determine the efficacy of eltrombopag for patients with CML or MF with persistent thrombocytopenia during therapy with a TKI or ruxoltinib. We enrolled 15 CML patients with persistent grade ≥3 thrombocytopenia (platelets ≤50 x 109/l) and six MF patients with platelets < 100 x 109/l after at least 3 months of therapy with a TKI or ruxolitinib. Patients received eltrombopag at a starting dose of 50 mg daily, with dose escalation to a maximum of 300 mg daily according to platelet response. Patients were followed with a weekly complete blood count until a stable platelet count was achieved. The target response was a complete response, defined as a platelet count ≥50 x 109/l for CML and ≥100 x 109/l for MF in at least 30% of subjects, sustained for 3 months while continuing TKIs or ruxolitinib therapy. Results: We enrolled 21 patients (CML = 15, MF = 6), with a median age of 60 years (range, 31-99 years). The median platelet count was 44 (range, 3-49) in patients with CML and 62 (range, 25-91) in those with MF. After a median duration of treatment of 18 months (range, 5-77 months), 11 of the 15 patients with CML achieved a complete platelet response at eltrombopag doses of 50–300 mg per day. The median peak platelet count among responders was 133 (range, 6-1225) x 109/l. Nine patients with CML experienced an improvement in cytogenetic response. In 5 patients with CML, the TKIs dose was increased and maintained while continuing eltrombopag. None of the 5 patients with MF had a sustained increase in platelet count to ≥100 x 109/l. No progression of disease was documented in any patient. Therapy was generally well tolerated. One patient (CML) discontinued therapy secondary to toxicity (persistent transaminitis with an accompanying lack of response). Conclusions: Eltrombopag demonstrated clinical efficacy in some patients with CML who were treated with TKIs. No similar benefit was observed in patients with MF who were treated with ruxolitinib. Eltrombopag might be a useful adjunct for patients with CML experiencing persistent thrombocytopenia. Clinical trial information: NCT01428635.