2023-07-03 09:26:20
This study presents the findings of the second phase of the EQOL-MDS trial, a randomized placebo-controlled phase II clinical trial. The trial focused on patients with low or intermediate-1 risk myelodysplastic syndrome (MDS) and persistent severe thrombocytopenia, who were treated with the thrombopoietin receptor agonist eltrombopag. Previously reported short-term results demonstrated the superiority of eltrombopag over placebo in inducing a platelet response. This report provides the complete data set for 169 patients following a median follow-up of 60 months.
The study revealed that 42.3% of patients treated with eltrombopag achieved a platelet response, compared to only 11.1% of those treated with placebo. Furthermore, at the cut-off data, 34.0% of patients who received eltrombopag were still responding to treatment, in contrast to 16.6% of patients in the placebo group. Importantly, both treatment groups had a similar incidence of progression to AML, with 17% of patients experiencing this outcome.
Importantly, no significant differences in survival times were observed between the eltrombopag and placebo groups. Overall, these findings highlight that eltrombopag treatment resulted in durable clinical efficacy and was well tolerated among patients with low- to intermediate-1 risk myelodysplastic syndrome.
SUMMARY
PURPOSE
In myelodysplastic syndromes (MDS), severe thrombocytopenia is associated with a poor prognosis. This multicenter trial presents the long-term efficacy and safety results of the second part of eltrombopag in patients with low-risk MDS and severe thrombocytopenia.
METHODS
In this blinded, randomized, placebo-controlled phase II trial of adult patients with MDS at low risk or intermediate risk-1 according to the International Prognostic Scoring System, patients with a stable platelet count (PLT) ( <30 × 103/mm3) received eltrombopag or placebo until disease progression. Primary endpoints were duration of platelet response (PLT-R; calculated from time of PLT-R to date of PLT-R loss, defined as bleeding/platelet count <30 × 103/mm3 or last observation date) and long-term safety and tolerability. Secondary endpoints included bleeding incidence and severity, platelet transfusions, quality of life, leukemia-free survival, progression-free survival, overall survival, and pharmacokinetics.
RESULTS
From 2011 to 2021, of the 325 patients evaluated, 169 patients were randomized to receive oral eltrombopag (N=112) or placebo (N=57) at a starting dose of 50 mg once daily, with a maximum of 300 mg. Platelet response (PLT-R) was observed in 47 of 111 (42.3%) patients treated with eltrombopag, compared with 6 of 54 (11.1%) patients in the placebo group (odds ratio, 5.9; 95% CI, 2.3 to 14.9, P < .001). In eltrombopag-treated patients, 12 of 47 (25.5%) lost platelet response, with a 60-month cumulative thrombocytopenia relapse-free survival of 63.6% (95% CI, 46.0 to 81.2). Clinically significant bleeding (WHO bleeding score ≥ 2) occurred less frequently in the eltrombopag group compared with the placebo group (incidence rate ratio, 0.54; 95% CI, 0.38 to 0.75; P = .0002). Although no differences in the frequency of grade 1-2 adverse events (AEs) were observed, a higher proportion of patients treated with eltrombopag experienced grade 3-4 AEs (χ2 = 9.5, P = .002). Acute myeloid leukemia (AML) progression and/or disease progression occurred in 17% (in both cases) of patients treated with eltrombopag and placebo, with no difference in survival times.
CONCLUSION
Eltrombopag was effective and relatively safe in low-risk MDS with severe thrombocytopenia.
Fuente
American society of Clinical Oncology
Esther Natalie Oliva, Marta Riva, Pasquale Niscola, Valeria Santini, Massimo Breccia, Valentina Giai, et al.
DOI: 10.1200/JCO.22.02699
Link: https://ascopubs.org/doi/10.1200/JCO.22.02699
1688378897
#Interim #Results #Phase #Randomized #PlaceboControlled #Clinical #Trial #EQOLMDS
