Eltrombopag

Eltrombopag is a new, orally active thrombopoietin-receptor (c-mpl) agonist that stimulates thrombopoiesis.

[Eltrombopag for refractory thrombocytopenia in patients with allogeneic hematopoietic stem cell transplantation].[Pubmed:28088971]

Zhonghua Xue Ye Xue Za Zhi. 2016 Dec 14;37(12):1065-1069.

Objective: To evaluate the efficacy and safety of Eltrombopag in post-HSCT thrombocytopenia. Methods: A total of 10 patients who underwent post-HSCT thrombocytopenia at Peking University center, who had been treated with Eltrombopag, were retrospectively evaluated. Results: Of the 10 cases, 5 males and 5 females with a median of 34 years old (range, 17-54 years), 5 patients were acute myeloid leukemia, 3 with acute lymphoid leukemia and 2 with severe aplastic anemia. Nine patients had undergone haplo-identical donor transplantation, and one patient was a matched related recipient. All patients had failed prior treatment for thrombocytopenia before Eltrombopag started. The median time when Eltrombopag started was 221 days (range, 73-917 days) after transplantation. Five patients (50%) had achieved CR. The cumulative incidence of 30-day CR was 35.7%. The median time to platelet recovery >/= 50 x 10(9)/L without transfusion support was 16 days (range, 10-56 days). At the last follow-up, three of the patients with CR had withdrawal Eltrombopag and remained normal platelet counts. No patients experienced drug-related adverse events. Conclusion: Eltrombopag is effective and well tolerated in patients with refractory post-HSCT thrombocytopenia.

Eltrombopag versus placebo for low-risk myelodysplastic syndromes with thrombocytopenia (EQoL-MDS): phase 1 results of a single-blind, randomised, controlled, phase 2 superiority trial.[Pubmed:28162984]

Lancet Haematol. 2017 Mar;4(3):e127-e136.

BACKGROUND: In myelodysplastic syndromes, thrombocytopenia is associated with mortality, but treatments in this setting are scarce. We tested whether Eltrombopag, a thrombopoietin receptor agonist, might be effective in improving thrombocytopenia in lower-risk myelodysplastic syndromes and severe thrombocytopenia. METHODS: EQoL-MDS was a single-blind, randomised, controlled, phase 2 superiority trial of adult patients with low-risk or International Prognostic Scoring System intermediate-1-risk myelodysplastic syndromes and severe thrombocytopenia. Patients with a stable platelet count of lower than 30 x 10(9) platelets per L, aged at least 18 years, with refractoriness, ineligibility to receive treatment with alternative medications, or relapse while receiving treatment with alternative medications were included in this trial. Patients were randomly assigned (2:1) to receive Eltrombopag (50 mg to 300 mg) or placebo for at least 24 weeks and until disease progression and were masked to treatment allocation. Here, we report the results in the intention-to-treat population of the first phase of the trial, for which the primary endpoints were the proportion of patients achieving a platelet response within 24 weeks and safety. The interim analysis presented here was protocol-specified and used a two-sided significance level of 0.001 and a p value at or below this limit for both primary endpoints to indicate the need for early trial termination. Duration of platelet transfusion independence, duration of response, overall survival, leukaemia-free survival, and pharmacokinetics will be reported at the end of the phase 2 portion of the trial. This trial is registered with EudraCT, number 2010-022890-33. FINDINGS: Between June 13, 2011, and June 17, 2016, we enrolled 90 participants for the first phase of the trial. The median follow-up time to assess platelet responses was 11 weeks (IQR 4-24). Platelet responses occurred in 28 (47%) of 59 patients in the Eltrombopag group versus one (3%) of 31 patients in the placebo group (odds ratio 27.1 [95% CI 3.5-211.9], p=0.0017). During the follow-up, 21 patients had at least one severe bleeding event (WHO bleeding score >/=2). There were a higher number of bleeders in the placebo (13 [42%] of 31 patients) than in the Eltrombopag arm (eight [14%] of 59 patients; p=0.0025). 52 grade 3-4 adverse events occurred in 27 (46%) of 59 patients in the Eltrombopag group versus nine events in five (16%) of 31 patients in the placebo group (chi(2)=7.8, p=0.0053, stopping rule not reached). The outcome acute myeloid leukaemia evolution or disease progression occurred in seven (12%) of 59 patients in the Eltrombopag group versus five (16%) of 31 patients in the placebo group (chi(2)=0.06, p=0.81). INTERPRETATION: Eltrombopag is well-tolerated in patients with lower-risk myelodysplastic syndromes and severe thrombocytopenia and is clinically effective in raising platelet counts and reducing bleeding events. The assessment of long-term safety and efficacy of Eltrombopag and its effect on survival (phase 2 part of study) is still ongoing. FUNDING: Associazione QOL-ONE.