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

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 × 109/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 × 109/L).

Methods: Patients were stratified according to baseline platelet count into stratum 1 (S1, 75 to <100 × 109/L) or stratum 2 (S2, 50 to <75 × 109/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 × 109/L.

Registration: ClinicalTrials.gov NCT01317875.

Keywords: myelofibrosis; ruxolitinib; thrombocytopenia.

Conflict of interest statement

Competing interests: PG reports payment of honoraria from Abbvie and Novartis; travel support from Abbvie, Novartis and Sanofi; participation in advisory boards from Abbvie and Novartis. JJK reports consulting fees from Abbvie and Novartis; payment of honoraria from AOP Orphan and Novartis; participation in advisory boards from BMS/Celgene and Incyte. AMV reports consulting fees from Abbvie, Blueprint, BMS/Celgene, Incyte, Novartis and Roche; payment of honoraria from Abbvie, BMS and Novartis. HM reports payment of honoraria from Novartis. LP reports payment of honoraria from Novartis. GH reports payment of honoraria from Novartis. SV reports research grants from AstraZeneca, Blueprint, Celgene, CTI BioPharma Corp., Genentech, Gilead, Incyte, Italpharma, Novartis, NS Pharma, Pharma Essentia, Promedior, Protagonist Therapeutics, Roche, Sierra Oncology; consulting fees from Celgene, Constellation, Incyte, Novartis, Pragmatist, Sierra. FBoyer reports consulting fees from Novartis. DN reports research funding from Daiichi; participation on speaker’s bureau from Amgen and Novartis; membership on an entity’s board of directors or advisory committees from Cellectis. AML reports institutional grants from Abbvie, Archigen, Beigene, Celgene, Fibrogen, GSK, Incyte, Janssen, Karyopharm, Morphosys, Novartis, Onconova, Oncopeptides, Pfizer, Roche, Sanofi, Servier, Takeda, Verastem; consulting fees from Incyte; payment of honoraria from Abbvie, BMS, Celgene, IQVIA, Janssen, Servier; travel support from Abbvie, BMS, Celgene, IQVIA, Janssen, Novartis, Roche, Sanofi, Takeda, Verastem; participation in advisory boards from Amgen and Servier. CH reports institutional grants from BMS/Celgene, Constellation Pharmaceuticals and Novartis; consulting fees from Novartis; payment of honoraria from Abbvie, AOP Orphan Pharmaceuticals, BMS/Celgene, CTI BioPharma Corp, Incyte, Janssen and Novartis; participation in advisory boards from AOP Orphan Pharmaceuticals, Celgene, Constellation Pharmaceuticals, CTI BioPharma Corp, Galecto, Geron, Incyte, Keros, Novartis, Promedior, Roche, Sierra Oncology. PR, MW, DK, and KS are employers and stockholders of Novartis. PAWTB reports participation in advisory boards from BMS/Celgene. HG reports research grants from AOP Orphan and Novartis; consulting fees from AOP Orphan, Myelopro, Novartis; payment of honoraria from AOP Orphan, BMS/Celgene, Janssen, Novartis. FBarraco, MD, and EP report no conflicts of interest.

© The Author(s), 2022.

Figures

Figure 1.

Spleen length response. Waterfall plot of best response in spleen length (with respect to baseline) at any time during the study by stratum, MSSD cohort. MSSD, maximum safe starting dose.

Figure 2.

Spleen length over time by ruxolitinib dose. Box plot presentation of spleen length over time by ruxolitinib dosing regimen. Solid black line crosses median values at each time point. Plot shows boxes (25th–75th percentiles) with whiskers (vertical lines) extending to the furthest value within 1.5 × IQR. Dots show outliers. AM, morning dose; IQR, interquartile range; PM, evening dose.