Background: Thrombocytopenia is a common feature of myelofibrosis (MF), a myeloproliferative neoplasm driven by dysregulated JAK/STAT signaling; however, pivotal trials assessing the efficacy of ruxolitinib (a JAK1/2 inhibitor) excluded MF patients with low platelet counts (<100 x 10(9)/L).Objectives: Determination of the maximum safe starting dose (MSSD) of ruxolitinib was the primary endpoint, with long-term safety and efficacy as secondary and exploratory endpoints, respectively.Design: EXPAND (NCT01317875) was a phase 1b, open-label, ruxolitinib dose-finding study in patients with MF and low platelet counts (50 to <100 x 10(9)/L).Methods: Patients were stratified according to baseline platelet count into stratum 1 (S1, 75 to <100 x 10(9)/L) or stratum 2 (S2, 50 to <75 x 10(9)/L). Previous analyses established the MSSD at 10 mg twice daily (bid); long-term results are reported here.Results: Of 69 enrolled patients, 38 received ruxolitinib at the MSSD (S1, n = 20; S2, n = 18) and are the focus of this analysis. The incidence of adverse events was consistent with the known safety profile of ruxolitinib, with thrombocytopenia (S1, 50%; S2, 78%) and anemia (S1, 55%; S2, 44%) the most frequently reported adverse events and no new or unexpected safety signals. Substantial clinical benefits were observed for patients in both strata: 50% (10/20) and 67% (12/18) of patients in S1 and S2, respectively, achieved a spleen response (defined as >= 50% reduction in spleen length from baseline) at any time during the study.Conclusion: The final safety and efficacy results from EXPAND support the use of a 10 mg bid starting dose of ruxolitinib in patients with MF and platelet counts 50 to <100 x 10(9)/L.

Efficacy and safety of ruxolitinib in patients with myelofibrosis and low platelet count (50 × 109/L to <100 × 109/L) at baseline: the final analysis of EXPAND / Guglielmelli, Paola; Kiladjian, Jean-Jacques; Vannucchi, Alessandro M; Duan, Minghui; Meng, Haitao; Pan, Ling; He, Guangsheng; Verstovsek, Srdan; Boyer, Françoise; Barraco, Fiorenza; Niederwieser, Dietger; Pungolino, Ester; Liberati, Anna Marina; Harrison, Claire; Roussou, Pantelia; Wroclawska, Monika; Karumanchi, Divyadeep; Sinclair, Karen; Te Boekhorst, Peter A W; Gisslinger, Heinz. - In: THERAPEUTIC ADVANCES IN HEMATOLOGY. - ISSN 2040-6207. - ELETTRONICO. - 13:(2022), pp. 1-13. [10.1177/20406207221118429]

Efficacy and safety of ruxolitinib in patients with myelofibrosis and low platelet count (50 × 109/L to <100 × 109/L) at baseline: the final analysis of EXPAND

Guglielmelli, Paola
Writing – Original Draft Preparation
;
Vannucchi, Alessandro M
Writing – Original Draft Preparation
;
2022

Abstract

Background: Thrombocytopenia is a common feature of myelofibrosis (MF), a myeloproliferative neoplasm driven by dysregulated JAK/STAT signaling; however, pivotal trials assessing the efficacy of ruxolitinib (a JAK1/2 inhibitor) excluded MF patients with low platelet counts (<100 x 10(9)/L).Objectives: Determination of the maximum safe starting dose (MSSD) of ruxolitinib was the primary endpoint, with long-term safety and efficacy as secondary and exploratory endpoints, respectively.Design: EXPAND (NCT01317875) was a phase 1b, open-label, ruxolitinib dose-finding study in patients with MF and low platelet counts (50 to <100 x 10(9)/L).Methods: Patients were stratified according to baseline platelet count into stratum 1 (S1, 75 to <100 x 10(9)/L) or stratum 2 (S2, 50 to <75 x 10(9)/L). Previous analyses established the MSSD at 10 mg twice daily (bid); long-term results are reported here.Results: Of 69 enrolled patients, 38 received ruxolitinib at the MSSD (S1, n = 20; S2, n = 18) and are the focus of this analysis. The incidence of adverse events was consistent with the known safety profile of ruxolitinib, with thrombocytopenia (S1, 50%; S2, 78%) and anemia (S1, 55%; S2, 44%) the most frequently reported adverse events and no new or unexpected safety signals. Substantial clinical benefits were observed for patients in both strata: 50% (10/20) and 67% (12/18) of patients in S1 and S2, respectively, achieved a spleen response (defined as >= 50% reduction in spleen length from baseline) at any time during the study.Conclusion: The final safety and efficacy results from EXPAND support the use of a 10 mg bid starting dose of ruxolitinib in patients with MF and platelet counts 50 to <100 x 10(9)/L.
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Guglielmelli, Paola; Kiladjian, Jean-Jacques; Vannucchi, Alessandro M; Duan, Minghui; Meng, Haitao; Pan, Ling; He, Guangsheng; Verstovsek, Srdan; Boyer, Françoise; Barraco, Fiorenza; Niederwieser, Dietger; Pungolino, Ester; Liberati, Anna Marina; Harrison, Claire; Roussou, Pantelia; Wroclawska, Monika; Karumanchi, Divyadeep; Sinclair, Karen; Te Boekhorst, Peter A W; Gisslinger, Heinz
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2158/1286013
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