Abstract
Abstract 3281
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).
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.
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.
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 data
| Patient | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
|---|---|---|---|---|---|---|---|---|---|
| Age (yrs) | 43 | 51 | 54 | 46 | 79 | 29 | 50 | 51 | 38 |
| Sex | M | M | F | F | F | M | F | F | F |
| ITP duration (years)1 | 0.1 | 1.3 | 0.6 | 0.6 | 3.3 | 5.5 | 4.2 | NA | 0.8 |
| Splenectomy | – | Yes | – | – | – | Yes | Yes | – | Yes |
| Prior ITP therapies | 2 | 2 | 3 | 2 | 5 | 4 | 3 | NA | 2 |
| Baseline plt count2 | 161 | 32 | 358 | 95 | 11 | 13 | 42 | 49 | 38 |
| Romiplostim starting dose | 1 | 6 | 2 | 1 | 2 | 15 | 1 | 1 | 1 |
| Range romiplostim dose | 1 | 1–65 | 1–25 | 1 | 1–45 | 2–155 | 15 | 1–35 | 1–8 |
| Romiplostim 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 study3 | 161–255 | 32–809 | 134–638 | 83–267 | 11–746 | 9–749 | 30–437 | 31–736 | 4–849 |
| Plt count before last romiplostim dose | 233 | 380 | 272 | 267 | 313 | 303 | 437 | 309 | 471 |
| Weeks after romiplostim discontinued4 | 77 | 26 | 36 | 41 | 166 | 125 | 88 | 153 | 47 |
| Plt range after romiplostim discontinued | 94–174 | 148–511 | 213–411 | 76–487 | 97–496 | 262–611 | 72–255 | 225–467 | 125–366 |
| Post–study follow–up6 | Plt stable | NA | NA | NA | 18 m later required ITP Rx7 | Plt stable | Plt stable | NA | Plt stable |
| Patient | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
|---|---|---|---|---|---|---|---|---|---|
| Age (yrs) | 43 | 51 | 54 | 46 | 79 | 29 | 50 | 51 | 38 |
| Sex | M | M | F | F | F | M | F | F | F |
| ITP duration (years)1 | 0.1 | 1.3 | 0.6 | 0.6 | 3.3 | 5.5 | 4.2 | NA | 0.8 |
| Splenectomy | – | Yes | – | – | – | Yes | Yes | – | Yes |
| Prior ITP therapies | 2 | 2 | 3 | 2 | 5 | 4 | 3 | NA | 2 |
| Baseline plt count2 | 161 | 32 | 358 | 95 | 11 | 13 | 42 | 49 | 38 |
| Romiplostim starting dose | 1 | 6 | 2 | 1 | 2 | 15 | 1 | 1 | 1 |
| Range romiplostim dose | 1 | 1–65 | 1–25 | 1 | 1–45 | 2–155 | 15 | 1–35 | 1–8 |
| Romiplostim 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 study3 | 161–255 | 32–809 | 134–638 | 83–267 | 11–746 | 9–749 | 30–437 | 31–736 | 4–849 |
| Plt count before last romiplostim dose | 233 | 380 | 272 | 267 | 313 | 303 | 437 | 309 | 471 |
| Weeks after romiplostim discontinued4 | 77 | 26 | 36 | 41 | 166 | 125 | 88 | 153 | 47 |
| Plt range after romiplostim discontinued | 94–174 | 148–511 | 213–411 | 76–487 | 97–496 | 262–611 | 72–255 | 225–467 | 125–366 |
| Post–study follow–up6 | Plt stable | NA | NA | NA | 18 m later required ITP Rx7 | Plt stable | Plt stable | NA | Plt stable |
Plt, platelet, NA = not available. Plt counts, × 109/L; romiplostim dose, μg/kg/week.
At initial romiplostim trial
For the latter part of the extension, baseline platelet count could be of any level.
Platelet counts for the 4 weeks after IVIg (as occurred with patients 8 and 9) were excluded.
Platelet counts >50×109/L lasted until the end of the study for all patients.
Romiplostim treatment was not continuous in these patients.
Where follow-up was available
18 months post-study, this patient developed epistaxis, bruising, and petechiae, for which she received prednisone for 1 week. Romiplostim was also restarted.
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.
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