Purpose: In myelodysplastic syndromes (MDS), severe thrombocytopenia is associated with poor prognosis. This multicenter trial presents the second-part long-term efficacy and safety results of eltrombopag in patients with low-risk MDS and severe thrombocytopenia. Methods: In this single-blind, randomized, placebo-controlled, phase-II trial of adult patients with International Prognostic Scoring System low- or intermediate-1-risk MDS, patients with a stable platelet (PLT) count (<30 × 103/mm3) received eltrombopag or placebo until disease progression. Primary end points were duration of PLT response (PLT-R; calculated from the time of PLT-R to date of loss of PLT-R, defined as bleeding/PLT count <30 × 103/mm3 or last date in observation) and long-term safety and tolerability. Secondary end points included incidence and severity of bleeding, PLT transfusions, quality of life, leukemia-free survival, progression-free survival, overall survival and pharmacokinetics. Results: From 2011 to 2021, of 325 patients screened, 169 patients were randomly assigned oral eltrombopag (N = 112) or placebo (N = 57) at a starting dose of 50 mg once daily to maximum of 300 mg. PLT-R, with 25-week follow-up (IQR, 14-68) occurred in 47/111 (42.3%) eltrombopag patients versus 6/54 (11.1%) in placebo (odds ratio, 5.9; 95% CI, 2.3 to 14.9; P < .001). In eltrombopag patients, 12/47 (25.5%) lost the PLT-R, with cumulative thrombocytopenia relapse-free survival at 60 months of 63.6% (95% CI, 46.0 to 81.2). Clinically significant bleeding (WHO bleeding score ≥ 2) occurred less frequently in the eltrombopag arm than in the placebo group (incidence rate ratio, 0.54; 95% CI, 0.38 to 0.75; P = .0002). Although no difference in the frequency of grade 1-2 adverse events (AEs) was observed, a higher proportion of eltrombopag patients experienced grade 3-4 AEs (χ2 = 9.5, P = .002). AML evolution and/or disease progression occurred in 17% (for both) of eltrombopag and placebo patients with no difference in survival times. Conclusion: Eltrombopag was effective and relatively safe in low-risk MDS with severe thrombocytopenia. This trial is registered with ClinicalTrials.gov identifier: NCT02912208 and EU Clinical Trials Register: EudraCT No. 2010-022890-33.

Eltrombopag for Low-Risk Myelodysplastic Syndromes With Thrombocytopenia: Interim Results of a Phase II, Randomized, Placebo-Controlled Clinical Trial (EQOL-MDS) / Oliva, Esther Natalie; Riva, Marta; Niscola, Pasquale; Santini, Valeria; Breccia, Massimo; Giai, Valentina; Poloni, Antonella; Patriarca, Andrea; Crisà, Elena; Capodanno, Isabella; Salutari, Prassede; Reda, Gianluigi; Cascavilla, Nicola; Ferrero, Dario; Guarini, Attilio; Tripepi, Giovanni; Iannì, Giuseppe; Russo, Emilio; Castelli, Andrea; Fattizzo, Bruno; Beltrami, Germana; Bocchia, Monica; Molteni, Alfredo; Fenaux, Pierre; Germing, Ulrich; Ricco, Alessandra; Palumbo, Giuseppe A.; Impera, Stefana; Di Renzo, Nicola; Rivellini, Flavia; Buccisano, Francesco; Stamatoullas-Bastard, Aspasia; Liberati, Anna Marina; Candoni, Anna; Delfino, Ilaria Maria; Arcadi, Maria Teresa; Cufari, Patrizia; Rizzo, Lorenzo; Bova, Irene; D'Errigo, Maria Grazia; Zini, Gina; Latagliata, Roberto. - In: JOURNAL OF CLINICAL ONCOLOGY. - ISSN 0732-183X. - ELETTRONICO. - 41:(2023), pp. 4486-4496. [10.1200/jco.22.02699]

Eltrombopag for Low-Risk Myelodysplastic Syndromes With Thrombocytopenia: Interim Results of a Phase II, Randomized, Placebo-Controlled Clinical Trial (EQOL-MDS)

Santini, Valeria;
2023

Abstract

Purpose: In myelodysplastic syndromes (MDS), severe thrombocytopenia is associated with poor prognosis. This multicenter trial presents the second-part long-term efficacy and safety results of eltrombopag in patients with low-risk MDS and severe thrombocytopenia. Methods: In this single-blind, randomized, placebo-controlled, phase-II trial of adult patients with International Prognostic Scoring System low- or intermediate-1-risk MDS, patients with a stable platelet (PLT) count (<30 × 103/mm3) received eltrombopag or placebo until disease progression. Primary end points were duration of PLT response (PLT-R; calculated from the time of PLT-R to date of loss of PLT-R, defined as bleeding/PLT count <30 × 103/mm3 or last date in observation) and long-term safety and tolerability. Secondary end points included incidence and severity of bleeding, PLT transfusions, quality of life, leukemia-free survival, progression-free survival, overall survival and pharmacokinetics. Results: From 2011 to 2021, of 325 patients screened, 169 patients were randomly assigned oral eltrombopag (N = 112) or placebo (N = 57) at a starting dose of 50 mg once daily to maximum of 300 mg. PLT-R, with 25-week follow-up (IQR, 14-68) occurred in 47/111 (42.3%) eltrombopag patients versus 6/54 (11.1%) in placebo (odds ratio, 5.9; 95% CI, 2.3 to 14.9; P < .001). In eltrombopag patients, 12/47 (25.5%) lost the PLT-R, with cumulative thrombocytopenia relapse-free survival at 60 months of 63.6% (95% CI, 46.0 to 81.2). Clinically significant bleeding (WHO bleeding score ≥ 2) occurred less frequently in the eltrombopag arm than in the placebo group (incidence rate ratio, 0.54; 95% CI, 0.38 to 0.75; P = .0002). Although no difference in the frequency of grade 1-2 adverse events (AEs) was observed, a higher proportion of eltrombopag patients experienced grade 3-4 AEs (χ2 = 9.5, P = .002). AML evolution and/or disease progression occurred in 17% (for both) of eltrombopag and placebo patients with no difference in survival times. Conclusion: Eltrombopag was effective and relatively safe in low-risk MDS with severe thrombocytopenia. This trial is registered with ClinicalTrials.gov identifier: NCT02912208 and EU Clinical Trials Register: EudraCT No. 2010-022890-33.
2023
41
4486
4496
Goal 3: Good health and well-being
Oliva, Esther Natalie; Riva, Marta; Niscola, Pasquale; Santini, Valeria; Breccia, Massimo; Giai, Valentina; Poloni, Antonella; Patriarca, Andrea; Crisà, Elena; Capodanno, Isabella; Salutari, Prassede; Reda, Gianluigi; Cascavilla, Nicola; Ferrero, Dario; Guarini, Attilio; Tripepi, Giovanni; Iannì, Giuseppe; Russo, Emilio; Castelli, Andrea; Fattizzo, Bruno; Beltrami, Germana; Bocchia, Monica; Molteni, Alfredo; Fenaux, Pierre; Germing, Ulrich; Ricco, Alessandra; Palumbo, Giuseppe A.; Impera, Stefana; Di Renzo, Nicola; Rivellini, Flavia; Buccisano, Francesco; Stamatoullas-Bastard, Aspasia; Liberati, Anna Marina; Candoni, Anna; Delfino, Ilaria Maria; Arcadi, Maria Teresa; Cufari, Patrizia; Rizzo, Lorenzo; Bova, Irene; D'Errigo, Maria Grazia; Zini, Gina; Latagliata, Roberto
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