Contributions
Abstract: O09
Type: Oral presentation
Session Topic: Inherited and acquired disorders of platelets
Presentation during EHA Scientific Conference on Bleeding Disorders:
On Thursday, September 15, 2016 from 09:00 - 10:30
Location: Rossini 1
Background
ITP is an autoimmune disorder with increased platelet destruction and insufficient platelet production. Romiplostim, a thrombopoietin receptor agonist, improves ITP outcomes compared with control (placebo or standard of care). Splenectomy removes a major site of sequestration of antibody-coated platelets, which might alter responsiveness to romiplostim or increase the risk of thrombosis or other complications. The efficacy and safety of romiplostim in splnx versus nonsplnx patients are not fully characterized.
Aims
This analysis evaluated safety and efficacy for splnx vs nonsplnx patients across 13 completed clinical studies of romiplostim in adults with ITP.
Methods
Data up to June 2014 were pooled. Informed consent was obtained in each ITP study. Safety was analyzed after ≥1 dose of romiplostim or control. Adverse event (AE) rates were adjusted for time of exposure. Efficacy included platelet response (any ≥50x109/L) and sustained platelet response (≥50x109/L ≥9 of 12 consecutive weeks). Four dose-finding studies that employed off-label doses were excluded from efficacy analyses.
Results
Safety was analyzed for 1111 patients (395 splnx; 716 nonsplnx). At baseline, splnx (vs nonsplnx) patients had longer median ITP duration (8.7 [95%CI: 7.7, 9.7] vs 1.6 [1.4, 2.0] yr), lower median platelet count (14.0 [12.0, 15.3] vs 19.3 [18.0, 21.0] x109/L), and a higher proportion with >3 prior ITP treatments (38% [33.2%, 43.0%] vs 12% [9.5%, 14.3%]). Splnx patients used more rescue medications (263.4 [95%CI: 251.5, 275.7] vs 153.3 [125.3, 138.8] per 100 pt-yr). Exposure-adjusted AE rates are provided in the table. AE rates per 100 pt-yr in the control group for both splnx (1861.1 [95%CI: 1616.9, 2132.2]) and nonsplnx (1052.6 [989.3, 1119.0]) patients were higher than in the respective romiplostim group. Efficacy data were analyzed for 1024 patients (376 splnx; 648 nonsplnx). Median platelet counts increased with romiplostim and platelet responses were stable over time in both subgroups. For romiplostim, rates of platelet response (≥50x109/L at least once) were 82% (95%CI: 78%, 86%) for splnx and 91% (89%, 93%) for nonsplnx patients (p<.0001), and rates of sustained platelet response (≥50x109/L ≥9 of 12 consecutive weeks) were 68% (63%, 72%) and 80% (77%, 83%), respectively (p<.0001).
Table. Duration-adjusted AE Rate per 100 pt-yr (95% CI)
| Splnx (702.0 pt-yr) | Nonsplnx (1129.7 pt-yr) | |
| Any AE | 1226.4 (1200.6, 1252.5) | 851.9 (835.0, 869.1) |
| Hemorrhage AEs | 266.1 (254.2, 278.4) | 140.8 (134.0, 147.9) |
| Infection AEs | 156.7 (147.6, 166.2) | 124.8 (118.4, 131.5) |
| Thrombotic AEs | 6.3 (4.6, 8.4) | 4.6 (3.4, 6.0) |
| Reticulin AEs* | 0.4 (0.2, 7.4) | 0.6 (0.2, 1.3) |
| Any serious AE | 68.1 (62.1, 74.5) | 44.1 (40.3, 48.1) |
| Any fatal AE | 1.6 (0.8, 2.8) | 2.7 (1.9, 3.9) |
| Any treatment-related AE | 123.1 (115.0, 131.6) | 82.1 (76.9, 87.6) |
*AEs reported as bone marrow reticulin fibrosis, myelofibrosis, or reticulin increase across 12 studies; excluded 1 ITP study specifically designed for bone marrow assessment (reported separately).
Summary/Conclusion
Removing a major site of platelet sequestration increased neither responsiveness nor toxicity of the thrombopoietin receptor agonist, romiplostim. In splnx patients, platelet response rates were lower, use of rescue medications was higher, and exposure-adjusted rates of hemorrhage AEs and infection AEs were higher. Differences between splnx and nonsplnx patients in disease duration/severity may have influenced concomitant treatments and safety/efficacy results. In conclusion, romiplostim safety generally was comparable between splnx and nonsplnx patients and platelet response rates were high in both populations.
Abstract: O09
Type: Oral presentation
Session Topic: Inherited and acquired disorders of platelets
Presentation during EHA Scientific Conference on Bleeding Disorders:
On Thursday, September 15, 2016 from 09:00 - 10:30
Location: Rossini 1
Background
ITP is an autoimmune disorder with increased platelet destruction and insufficient platelet production. Romiplostim, a thrombopoietin receptor agonist, improves ITP outcomes compared with control (placebo or standard of care). Splenectomy removes a major site of sequestration of antibody-coated platelets, which might alter responsiveness to romiplostim or increase the risk of thrombosis or other complications. The efficacy and safety of romiplostim in splnx versus nonsplnx patients are not fully characterized.
Aims
This analysis evaluated safety and efficacy for splnx vs nonsplnx patients across 13 completed clinical studies of romiplostim in adults with ITP.
Methods
Data up to June 2014 were pooled. Informed consent was obtained in each ITP study. Safety was analyzed after ≥1 dose of romiplostim or control. Adverse event (AE) rates were adjusted for time of exposure. Efficacy included platelet response (any ≥50x109/L) and sustained platelet response (≥50x109/L ≥9 of 12 consecutive weeks). Four dose-finding studies that employed off-label doses were excluded from efficacy analyses.
Results
Safety was analyzed for 1111 patients (395 splnx; 716 nonsplnx). At baseline, splnx (vs nonsplnx) patients had longer median ITP duration (8.7 [95%CI: 7.7, 9.7] vs 1.6 [1.4, 2.0] yr), lower median platelet count (14.0 [12.0, 15.3] vs 19.3 [18.0, 21.0] x109/L), and a higher proportion with >3 prior ITP treatments (38% [33.2%, 43.0%] vs 12% [9.5%, 14.3%]). Splnx patients used more rescue medications (263.4 [95%CI: 251.5, 275.7] vs 153.3 [125.3, 138.8] per 100 pt-yr). Exposure-adjusted AE rates are provided in the table. AE rates per 100 pt-yr in the control group for both splnx (1861.1 [95%CI: 1616.9, 2132.2]) and nonsplnx (1052.6 [989.3, 1119.0]) patients were higher than in the respective romiplostim group. Efficacy data were analyzed for 1024 patients (376 splnx; 648 nonsplnx). Median platelet counts increased with romiplostim and platelet responses were stable over time in both subgroups. For romiplostim, rates of platelet response (≥50x109/L at least once) were 82% (95%CI: 78%, 86%) for splnx and 91% (89%, 93%) for nonsplnx patients (p<.0001), and rates of sustained platelet response (≥50x109/L ≥9 of 12 consecutive weeks) were 68% (63%, 72%) and 80% (77%, 83%), respectively (p<.0001).
Table. Duration-adjusted AE Rate per 100 pt-yr (95% CI)
| Splnx (702.0 pt-yr) | Nonsplnx (1129.7 pt-yr) | |
| Any AE | 1226.4 (1200.6, 1252.5) | 851.9 (835.0, 869.1) |
| Hemorrhage AEs | 266.1 (254.2, 278.4) | 140.8 (134.0, 147.9) |
| Infection AEs | 156.7 (147.6, 166.2) | 124.8 (118.4, 131.5) |
| Thrombotic AEs | 6.3 (4.6, 8.4) | 4.6 (3.4, 6.0) |
| Reticulin AEs* | 0.4 (0.2, 7.4) | 0.6 (0.2, 1.3) |
| Any serious AE | 68.1 (62.1, 74.5) | 44.1 (40.3, 48.1) |
| Any fatal AE | 1.6 (0.8, 2.8) | 2.7 (1.9, 3.9) |
| Any treatment-related AE | 123.1 (115.0, 131.6) | 82.1 (76.9, 87.6) |
*AEs reported as bone marrow reticulin fibrosis, myelofibrosis, or reticulin increase across 12 studies; excluded 1 ITP study specifically designed for bone marrow assessment (reported separately).
Summary/Conclusion
Removing a major site of platelet sequestration increased neither responsiveness nor toxicity of the thrombopoietin receptor agonist, romiplostim. In splnx patients, platelet response rates were lower, use of rescue medications was higher, and exposure-adjusted rates of hemorrhage AEs and infection AEs were higher. Differences between splnx and nonsplnx patients in disease duration/severity may have influenced concomitant treatments and safety/efficacy results. In conclusion, romiplostim safety generally was comparable between splnx and nonsplnx patients and platelet response rates were high in both populations.