PDSA E-News: December 31, 2017


Breaking ITP Research from the 2017 American Society of Hematology (ASH) Annual Meeting


ASH Annual Meeting 2017 logoEach year the annual American Society of Hematology (ASH) meeting attracts thousands of clinicians and scientists, worldwide, to learn about and report on the latest hematology research. This year’s 2017 ASH meeting, held December 9 – 12 in Atlanta, GA featured the annual ITP Breakfast Meeting, coordinated by PDSA and two of our Medical Advisors, Dr. James Bussel and Dr. John Semple, who invited twelve hematologist investigators to present their cutting-edge ITP research. In this issue of the e-news, we report some trends. Watch for additional ASH findings in the 2017 winter issue of the PDSA quarterly newsletter, The Platelet News.

The ASH abstract numbers are shown in parentheses. You can search on the number and read the complete abstract at: https://ash.confex.com/ash/2017/webprogram/start.html.

Avatrombopag, a New TPO Agent, Demonstrates Superiority to Placebo in Phase 3 Trial

Novel Thrombopoietin-receptor agonist Avatrombopag boosts platelets within a week and demonstrates a durable response in phase 3 trials in comparison to placebo. Patients enrolled in the trial had not undergone splenectomy and only had one prior treatment for their ITP. Sixty-nine percent of patients raised their platelet counts above 50,000 without rescue therapy and none of the patients experienced any bleeding events while treated with Avatrombopag. Patients responded at day 8 of the trial, meaning the drug could also be used for a rescue therapy due to its quick response time.

A study on using this Thrombopoietin receptor agonist (like romiplostim-nplate and eltrombopag-promacta-revolade) in ITP was published in Blood (the leading Hematology Journal) in 2014 with similarly good results of increasing the platelet count . A separate study at this meeting also showed the good results of using Avatrombopag to prevent bleeding by increasing the platelet count connected with procedures in patients with liver disease.

Abstract 17. Jurczak, W., PhD, MD. (2017). Avatrombopag, a Novel Oral Thrombopoietin Receptor Agonist, Demonstrates Superiority to Placebo for the Treatment of Chronic Immune Thrombocytopenic Purpura in a Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled Trial [Abstract]. American Society of Hematology: Blood.


Predicting Bleeding Risk in Pediatric ITP

blood 1715010 640Severe bleeding occurs in 1 of every 10 adults with ITP and 1 of 5 children. Apart from low platelet counts (usually 10,000-20,000) and prior bleeds, researchers have generally been unable to establish a biological correlation between platelet count and bleeding. Preliminary findings of ongoing research conducted by PDSA Medical Advisor, Dr. Michele Lambert, at Children’s Hospital of Pennsylvania showed that both a lower fraction of immature platelets (which contain RNA, are more reactive to stimulation, and larger than mature platelets) as well as increased Platelet Factor 4, which regulates platelet count as an immune signaling molecule, both lead to a higher risk of bleeding independently from the platelet count. Practically speaking, in patients with very low counts these 2 markers may be able to distinguish which patient will have only bruises and petechiae and which one will have more bleeding than that.

Presentation only. Lambert, M., MD (2017). Pediatric ITP: Can We Predict Who is Most at Risk for Bleeding? [Oral Presentation]. American Society of Hematology: ITP Breakfast Meeting.


Decitabine Restores Immune Tolerance

SDZ31390Decitabine is a medication that has been in use in several medical conditions for a number of years. It is thought to change the DNA such that different parts of it are eligible to be activated with the right stimulation. A new ITP therapy, one study showed that Decitabine lessens the impact of ITP in two ways: platelet counts increase by increasing megakaryocyte maturation, which produce platelets. Decitabine also may restore immune tolerance by enhancing the function of regulatory T cells. ITP patients typically have a higher level of immune molecules that attack platelets; Decitabine is therefore able to suppress the number of aggressive immune cells, which in turn raises platelet count.

Abstract 229. Hou, M., MD, PhD. (2017). Low-Dose Decitabine Restores Immune Tolerance in ITP By Modulating Regulatory T Cells [Abstract]. American Society of Hematology: Blood.


Second Line ITP Treatments Improve Quality of Life and Fatigue in Children

girls 462072 640Over sixty percent of patients with ITP claim that their disease impacts their quality of life and over half of children with ITP say they are fatigued. While most children with ITP can be observed until a bleeding event, when they are typically treated with steroids or IVIG, there is a lack of information about how second-line therapies affect quality of life in kids and for their parents. The Pediatric ITP Consortium of North America examined the relationship between treatment with immunosuppressants (azathioprine, 6MP, mycophenolate mofetil and other medications), Rituximab, romiplostim, or eltrombopag in children and health-related quality of life. The physicians also looked at platelet count and bleeding severity and determined decision making factors for doctors when prescribing treatment. Health related quality of life improved on all treatments for both children and their parents; differences were difficult to quantitate because of the relatively small numbers.

Abstract 752. Grace, R., MD. (2017). Health Related Quality of Life and Fatigue Improve on Second Line Treatments in Pediatric Immune Thrombocytopenia (ITP) [Abstract]. American Society of Hematology: Blood.


Results from Phase 2 Trial of Rozanolixizumab, an Anti-FcRn Antibody

New ITP treatment Rozanolixizumab shows promising results in its phase two trial. Roz is an antibody that blocks the Neonatal Fc-receptor (FcRn). This receptor is responsible for recycling normal (and abnormal) IgG (antibody) and thus maintaining normal blood levels of IgG. Blocking this receptor by treatment with Rozanolixizumab decreases the amount of all IgG including the IgG that attacks platelets and their precursors. The drug therefore reduces serum IgG levels which improves platelet counts in patients with ITP. No increased rate of infections were seen but this reduction of IgG may not only reduce anti-platelet antibodies but also reduce normal IgG that helps to fight infections.

Abstract 15. Robak, T., MD, PhD. (2017). Phase II, Multiple Dose-Study of Anti-FcRn Antibody, Rozanolixizumab (UCB7665), in Patients with Primary Immune Thrombocytopenia: Interim Analysis [Abstract]. American Society of Hematology: Blood.


Long-Term Platelet Response to Fostamatinib in Adults with ITP

rigelPatients respond to new therapy Fostamatinib within two to 6 weeks of beginning treatment across 2 parallel-phase 3 trials. The primary endpoint was a consistent response with platelets over 50,000 on 4 of 6 study visits and was achieved in approximately 20% of cases. A count over 50,000 was achieved in 43% of patients. Sixty-eight percent of the stable responders maintained an elevated platelet count for 12+ months. Fostamatinib works by inhibiting platelet destruction in antibody-mediated platelet elimination by blocking a key part of the signaling mechanism in this critical pathway. The therapy is a good option for patients who have been unresponsive to other past ITP treatments due to its different mechanism of action.

Abstract 16. Bussel, J.B., MD. (2017). Long-Term Maintenance of Platelet Responses in Adult Patients with Persistent/Chronic Immune Thrombocytopenia Treated with Fostamatinib: 1-Year Efficacy and Safety Results. American Society of Hematology: Blood.



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