Sustained Hemostatic Platelet Counts in Adults with Immune Thrombocytopenia (ITP) Following Cessation of Treatment with the TPO Receptor Agonist Romiplostim: Report of 9 Cases,

Abstract

Abstract 3281▪▪This icon denotes a clinically relevant abstract Background:While romiplostim is often perceived as a long-term treatment for adults with chronic ITP, previous data suggest that some patients can maintain hemostatic platelet counts when romiplostim is permanently discontinued, as occurred in 7 of 83 romiplostim-treated patients in the pivotal trials (Kuter et al, Lancet 2008) and as presented at the 2011 EHA meeting (Newland et al, 2011). Methods:We describe 9 patients from an open-label extension study (N = 291, Bussel et al, Blood 2009) who had ITP of various durations unresponsive to treatments such as splenectomy, corticosteroids, IVIg, anti-D, danazol, azathioprine, and rituximab. Romiplostim was administered at the same dose as in the previous study or at 1 μg/kg (if patients had previously received placebo) and adjusted by no more than 1 μg/kg weekly to maintain platelet counts at 50–200×109/L. These patients were selected for this report because romiplostim was discontinued and hemostatic platelet counts maintained for at least 6 months. Results:In these cases, patients had ITP ranging in duration from 0.1 to 5.5 years and between 2 and 5 prior ITP therapies before entering romiplostim clinical trials (Table). The duration over which romiplostim was received in these cases (previous study and extension study combined) ranged from 37 to 139 weeks. No clinically significant bleeding (grade ≥3) was observed with romiplostim in these patients during the initial studies; during the open-label extension, epistaxis in Week 10 and gastrointestinal hemorrhage in Week 18 were reported for Case 6. Examination of these 9 cases indicates that there are no factors that appear to predict which patients, after discontinuing romiplostim, will achieve hemostatic platelet counts off treatment. Of note, as this was a post hoc analysis and not a prespecified endpoint, there may be other cases in which hemostatic platelet counts were maintained without romiplostim treatment. Summary/conclusions:Dose adjustment rules allow romiplostim to be discontinued when appropriate. These case reports indicate that some patients may not require romiplostim indefinitely. In the absence of other ITP treatments (e.g., immunosuppressive therapies), hemostatic platelet counts can be maintained in certain cases after cessation of romiplostim. We believe that more such cases will become known, allowing us to gain greater insights into which ITP patients are able to discontinue romiplostim and to the relationship to the natural history of ITP and possible remission. Potential mechanisms for this phenomenon should be explored, including what role is played by the improvement of T-regulatory cell function in the presence of hemostatic platelet counts (Bao et al, Blood 2010).Table Patient dataPatient123456789Age (yrs)435154467929505138SexMMFFFMFFFITP duration (years)10.11.30.60.63.35.54.2NA0.8Splenectomy–Yes–––YesYes–YesPrior ITP therapies2232543NA2Baseline plt count216132358951113424938Romiplostim starting dose1621215111Range romiplostim dose11–651–2511–452–155151–351–8Romiplostim over X weeks this study (parent study)3 (52)21 (16)23 (52)23 (52)41 (24)91 (24)105 (24)117 (6)139 (0)Plt range on romiplostim this study3161–25532–809134–63883–26711–7469–74930–43731–7364–849Plt count before last romiplostim dose233380272267313303437309471Weeks after romiplostim discontinued4772636411661258815347Plt range after romiplostim discontinued94–174148–511213–41176–48797–496262–61172–255225–467125–366Post–study follow–up6Plt stableNANANA18 m later required ITP Rx7Plt stablePlt stableNAPlt stablePlt, platelet, NA = not available. Plt counts, × 109/L; romiplostim dose, μg/kg/week.1At initial romiplostim trial2For the latter part of the extension, baseline platelet count could be of any level.3Platelet counts for the 4 weeks after IVIg (as occurred with patients 8 and 9) were excluded.4Platelet counts >50×109/L lasted until the end of the study for all patients.5Romiplostim treatment was not continuous in these patients.6Where follow-up was available718 months post-study, this patient developed epistaxis, bruising, and petechiae, for which she received prednisone for 1 week. Romiplostim was also restarted. [Display omitted] Disclosures:Bussel:Portola: Consultancy; Eisai: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Cangene: Research Funding; Genzyme: Research Funding; Immunomedics: Research Funding; Ligand: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Shionogi: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Sysmex: Research Funding. Rodeghiero:GSK: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Suppremol: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; LFB: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Lyons:Amgen: Consultancy, Honoraria, Research Funding, Speakers Bureau. Kessler:Amgen: Consultancy; Eisai: Consultancy; GlaxoSmithKline: Consultancy; Griffols: Consultancy, Research Funding. Terriou:Amgen: Honoraria; GSK: Honoraria. Stasi:GSK: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Suppremol: Consultancy, Honoraria; Nycomed: Honoraria; Bayer: Honoraria; Baxter: Honoraria. Chang:Amgen: Employment, Equity Ownership. Jun:Amgen: Employment, Equity Ownership.