Contributions
Abstract: P15
Type: Poster presentation
Presentation during EHA Scientific Conference on Bleeding Disorders:
On Friday, September 16, 2016 from 14:00 - 15:30
Location: Cristal + Coral
Background
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets. Pathophysiology of ITP is still under study, it involves platelet destruction and a relative platelet underproduction by bone marrow1. The new class of medications for ITP, called thrombopoietin receptor agonists (TRAs), stimulate megakaryocyte growth and increase platelet production. TRAs are currently administered as second line therapies of ITP2, the definition of their optimal schedule is however still debated. It is well known that romiplostim determines a direct dose-dependent increases in platelet counts, however the dose required to elicit a platelet response varies between individuals. Guidelines recommend to administer romiplostim weekly; however, the optimal dose interval for romiplostim has been poorly explored3,4.
Aims
Here we report our center's experience on the management of three adult Caucasian patients with refractory ITP successfully treated with biweekly administration of romiplostin.
Methods
Treatment was started with a weekly injection (1 mcg/kg), and the dose was escalated until a titrated dose was achieved to maintain platelet count> 50× 109/L ,at least for two consecutiveweeks. Patients were scheduled to a biweekly treatment and returned to a weekly administration in case of platelets count decrease to <30 × 109/L or in presence of active bleeding. All the patients were not-splenectomized and they had already received rituximab for previous ITP relapses.
Results
In one patient a weekly injection of 8 mcg/kg maintained platelet > 50 x109/L for one month , after the first month a biweekly administration of romiplostin was successfully continued for two years. Two patients achieved a platelet response with 3 mcg/kg and one with 4 mcg/kg. All them switched to a biweekly schedule after one month for stable platelet count. Platelets count of the first two patients fell to < 30 x 109/l after 4 and 2 months, respectively. All patients in our series responded upon treatment with romiplostin also when a weekly administration was required without bleeding. In the first case, a platelet response was achieved again with a dose of 5 mcg/kg, after one month, a biweekly schedule was again administered for seven months. The patient is currently treated with a biweekly treatment administration.
Conclusion
Our case series confirms the wide individual variation in the response to TRAs. In absence of identified factors that allow to predict these variations, attempts to prolong dose intervals should be made cautiously. TRAs treatment for ITP can be personalized.
References
1. Nugent D et al Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol. 2009;146:585–96.
2. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence- based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190–207.
3. Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006;355:1672–81.
4. Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther. 2004;76:628–38.
Abstract: P15
Type: Poster presentation
Presentation during EHA Scientific Conference on Bleeding Disorders:
On Friday, September 16, 2016 from 14:00 - 15:30
Location: Cristal + Coral
Background
Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets. Pathophysiology of ITP is still under study, it involves platelet destruction and a relative platelet underproduction by bone marrow1. The new class of medications for ITP, called thrombopoietin receptor agonists (TRAs), stimulate megakaryocyte growth and increase platelet production. TRAs are currently administered as second line therapies of ITP2, the definition of their optimal schedule is however still debated. It is well known that romiplostim determines a direct dose-dependent increases in platelet counts, however the dose required to elicit a platelet response varies between individuals. Guidelines recommend to administer romiplostim weekly; however, the optimal dose interval for romiplostim has been poorly explored3,4.
Aims
Here we report our center's experience on the management of three adult Caucasian patients with refractory ITP successfully treated with biweekly administration of romiplostin.
Methods
Treatment was started with a weekly injection (1 mcg/kg), and the dose was escalated until a titrated dose was achieved to maintain platelet count> 50× 109/L ,at least for two consecutiveweeks. Patients were scheduled to a biweekly treatment and returned to a weekly administration in case of platelets count decrease to <30 × 109/L or in presence of active bleeding. All the patients were not-splenectomized and they had already received rituximab for previous ITP relapses.
Results
In one patient a weekly injection of 8 mcg/kg maintained platelet > 50 x109/L for one month , after the first month a biweekly administration of romiplostin was successfully continued for two years. Two patients achieved a platelet response with 3 mcg/kg and one with 4 mcg/kg. All them switched to a biweekly schedule after one month for stable platelet count. Platelets count of the first two patients fell to < 30 x 109/l after 4 and 2 months, respectively. All patients in our series responded upon treatment with romiplostin also when a weekly administration was required without bleeding. In the first case, a platelet response was achieved again with a dose of 5 mcg/kg, after one month, a biweekly schedule was again administered for seven months. The patient is currently treated with a biweekly treatment administration.
Conclusion
Our case series confirms the wide individual variation in the response to TRAs. In absence of identified factors that allow to predict these variations, attempts to prolong dose intervals should be made cautiously. TRAs treatment for ITP can be personalized.
References
1. Nugent D et al Pathogenesis of chronic immune thrombocytopenia: increased platelet destruction and/or decreased platelet production. Br J Haematol. 2009;146:585–96.
2. Neunert C, Lim W, Crowther M, Cohen A, Solberg L Jr, Crowther MA. The American Society of Hematology 2011 evidence- based practice guideline for immune thrombocytopenia. Blood. 2011;117:4190–207.
3. Bussel JB, Kuter DJ, George JN, McMillan R, Aledort LM, Conklin GT, et al. AMG 531, a thrombopoiesis-stimulating protein, for chronic ITP. N Engl J Med. 2006;355:1672–81.
4. Wang B, Nichol JL, Sullivan JT. Pharmacodynamics and pharmacokinetics of AMG 531, a novel thrombopoietin receptor ligand. Clin Pharmacol Ther. 2004;76:628–38.