Mechanisms of response to treatment in autoimmune thrombocytopenic purpura, FcgammaRI and FcgammaRIII on splenic macrophages mediate phagocytosis of anti-glycoprotein IIb/IIIa autoantibody-opsonized platelets in immune thrombocytopenia, The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia, The serum levels of the cytokines involved in the Th17 and Th1 cell commitment are increased in individuals with borderline thrombocytopenia, Analysis of regulatory T-cell changes in patients with idiopathic thrombocytopenic purpura receiving B cell-depleting therapy with rituximab, Cell-mediated lysis of autologous platelets in chronic idiopathic thrombocytopenic purpura, Influence of monoclonal antiplatelet glycoprotein antibodies on in vitro human megakaryocyte colony formation and proplatelet formation, An antibody cytotoxic to megakaryocyte progenitor cells in a patient with immune thrombocytopenic purpura, Differences in serum cytokine levels in acute and chronic autoimmune thrombocytopenic purpura: relationship to platelet phenotype and antiplatelet T-cell reactivity. Complementary & Alternative Medicine (CAM), Talking to Others about Your Advanced Cancer, Coping with Your Feelings During Advanced Cancer, Emotional Support for Young People with Cancer, Young People Facing End-of-Life Care Decisions, Late Effects of Childhood Cancer Treatment, Tech Transfer & Small Business Partnerships, Frederick National Laboratory for Cancer Research, Milestones in Cancer Research and Discovery, Step 1: Application Development & Submission, National Cancer Act 50th Anniversary Commemoration, How to Work With Your Health Insurance Plan, Questions to Ask about Treatment Clinical Trials, Drugs Approved for Different Types of Cancer, Drugs Approved for Conditions Related to Cancer, U.S. Department of Health and Human Services. Although neither romiplostim nor eltrombopag is approved for patients with MDS, treatment may improve platelet counts and reduce bleeding in a number of patients.190 In one of the first of these studies, treatment with romiplostim compared with placebo initially was thought to increase leukemic blast levels in blood. Giagounidis A, Mufti GJ, Fenaux P, et al. Use of romiplostim in pediatric patients (including term neonates) acutely exposed to myelosuppressive doses of radiation is based on efficacy studies conducted in animals; studies in humans could not be conducted because of ethical and feasibility reasons. Bunin DI, Bakke J, Green CE, Javitz HS, Fielden M, Chang PY. Romiplostim (Nplate ) as an effective radiation countermeasure to improve survival and platelet recovery in mice. Successful treatment of post-transplant thrombocytopenia with romiplostim in a pediatric patient with X-linked chronic granulomatous disease, Eltrombopag for delayed platelet recovery and secondary thrombocytopenia following allogeneic stem cell transplantation in children. Romiplostim Treatment of Chemotherapy-Induced Thrombocytopenia. Thrombopoietin receptor agonists such as romiplostim, eltrombopag, and avatrombopag can be used to temporarily increase platelet count or as a long-term therapy to maintain a desired platelet count goal. To evaluate the efficacy of romiplostim for the treatment of CIT in patients receiving chemotherapy for the treatment of NSCLC, ovarian cancer, or breast cancer measured by the ability to administer on-time, full-dose chemotherapy Detailed Description: The effectiveness of romiplostim for this use was only studied in animals, because it could not be studied in people. Registro delle prove cliniche. The https:// ensures that you are connecting to the Romiplostim was initiated at 1-2 mcg/kg weekly, with dose escalation by 1 mcg/kg per week until recovery of platelets (100 10 (9)/L). These autoantibodies target platelets for destruction by macrophages in the spleen or liver through activation of Fc receptors, a process controlled by spleen Syk. Kato T, Matsumoto A, Ogami K, Tahara T, Morita H, Miyazaki H. Native thrombopoietin: structure and function, Milestones in understanding platelet production: a historical overview, Multifaceted roles of thrombopoietin in hematopoietic stem cell regulation, Promotion of megakaryocyte progenitor expansion and differentiation by the c-Mpl ligand thrombopoietin, The purification of megapoietin: a physiological regulator of megakaryocyte growth and platelet production, Thrombopoietin (c-mpl ligand) acts synergistically with erythropoietin, stem cell factor, and interleukin-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro, Thrombopoietin, the ligand for the Mpl receptor, synergizes with steel factor and other early acting cytokines in supporting proliferation of primitive hematopoietic progenitors of mice, Mpl ligand (MGDF) alone and in combination with stem cell factor (SCF) promotes proliferation and survival of human megakaryocyte, erythroid and granulocyte/macrophage progenitors, The effect of thrombopoietin on the proliferation and differentiation of murine hematopoietic stem cells, Romiplostim in patients with refractory aplastic anaemia previously treated with immunosuppressive therapy: a dose-finding and long-term treatment phase 2 trial, The progression of severe aplastic anemia to hypoplastic leukemia in a long-term observation after the administration of pegylated rHuMGDF. Literature review of TPOR agonists for CIT [abstract 1563P]. Radiomitigation by Melatonin in C57BL/6 Mice: Possible Implications as Adjuvant in Radiotherapy and Chemotherapy. Here, we briefly present the treatment modalities for H-ARS. In the final patient, antibodies were detected at the end of the study.89 In another long-term study assessing the efficacy and safety of romiplostim in children with ITP (N=203), 7 patients developed neutralizing antibodies to romiplostim; all discontinued treatment. Nplate is also approved for the treatment of thrombocytopenia in: Please see your health care professional for more information about your specific medical condition and the use of this drug. The combination of romiplostim and pegfilgrastim resulted in the least severe thrombocytopenia and earliest recovery.147.
Romiplostim Receives FDA Approval for Pediatric ITP - Targeted Oncology The authors report no other conflicts of interest in this work. Yamanouchi J, Hato T, Kunishima S, Niiya T, Nakamura H, Yasukawa M. A novel MYH9 mutation in a patient with MYH9 disorders and platelet size-specific effect of romiplostim on macrothrombocytopenia, Thrombopoietin mutation in congenital amegakaryocytic thrombocytopenia treatable with romiplostim, Bone marrow failure unresponsive to bone marrow transplant is caused by mutations in thrombopoietin, Eltrombopag for the treatment of the inherited thrombocytopenia deriving from MYH9 mutations. nplate administration. Adriana Balduzzi has received honoraria, advisory board, lectures, speakers bureaus, and/or meeting/travel assistance from Amgen, Novartis, Medac, and Neovii, outside the submitted work. Bethesda, MD 20894, Web Policies It is not a substitute for medical advice. Case reports, Romiplostim for therapy-related thrombocytopenia in pediatric malignancies [Brief report]. The utility of romiplostim to prevent or treat CIT has been examined in preclinical studies,109 case reports,110,111 retrospective analyses,112114 and clinical studies.115117 Preclinical data from McElroy et al indicate that there is an inverse relationship between platelet counts and endogenous TPO concentration in mice subjected to chemotherapy/radiation therapy; romiplostim enhanced platelet recovery particularly when administered in high doses (100 g/kg; an order of magnitude above the highest recommended dose in ITP of 10 g/kg).5,6,109 A phase 2 trial investigated romiplostim compared with observation in patients with solid tumors.117 Because of promising results from an interim analysis that included a crossover part and lack of evidence that untreated control patients would experience corrected thrombocytopenia with additional time, the study was converted to a single-arm, open-label study after institutional review board approval; in 60 patients with solid tumors and thrombocytopenia, romiplostim was able to significantly increase platelet count, reverse CIT, and reduce the recurrence of CIT in approximately 85% of patients. A retrospective evaluation of chemotherapy dose intensity and supportive care for early-stage breast cancer in a curative setting. James B Bussel, Gerald Soff, [], and John W Semple. They include but are not limited to policies relating to evolving medical technologies and procedures, as well as pharmacy policies. It works by causing the cells in the bone marrow to produce more platelets. (CIT) from lenalidomide or from radiation therapy alone will not be allowed In the present study, a single administration of romiplostim (RP), an approved thrombopoietin receptor agonist, produced a 100% survival rate in C57BL/6 J mice exposed to a lethal dose (7 Gy) of. The latter appears likely, however, in a number of the cases discussed previously. Romiplostim (Nplate) for injection is available as 125 mcg, 250 mcg or 500 mcg of deliverable romiplostim as a lyophilized powder in single-dose vials. The drug can be used to treat adults and children." [7] References [ edit] ^ a b Waknine, Yael (4 September 2008). Thrombopoietin receptor agonist (TPO-RA) treatment raises platelet counts and reduces anti-platelet antibody levels in mice with immune thrombocytopenia (ITP). Romiplostim improves platelet recovery after UCB transplant [abstract no. The site is secure. A recent case report of an atypical presentation of WiskottAldrich syndrome in an infant included the use of romiplostim and platelet transfusions to maintain platelet counts.183 In a study of nine patients with WiskottAldrich syndrome/X-linked thrombocytopenia, treatment with eltrombopag was found to be associated with beneficial effects on platelet count.184 The study also found that platelet function and ability to be activated appeared to be relatively normal, and the increased bleeding tendency at a given platelet count was thought to be due to microthrombocytopenia rather than to intrinsic platelet abnormalities.184 One patient in this study discontinued eltrombopag because of lack of response and switched to romiplostim and experienced a greater increase in platelet count and less bleeding.184, Patients with chronic liver disease often have thrombocytopenia, particularly those with cirrhosis.185 In patients with advanced chronic liver disease, TPO declines as a result of splenomegaly and hepatic damage such that the liver cannot make even normal amounts of TPO. Do not inject into an area that has scars or stretch marks or is tender, red, bruised, or hard. 2016 Sep;55(9):1045-58. doi: 10.1007/s40262-016-0382-7. Romiplostim is also given to people whose ability to make platelets is reduced due to exposure to large amounts of radiation. The best treatment approaches under such circumstances (ie, TPO-RA versus intravenous immunoglobulin, dose, and timing of treatment) have been raised for the use of eltrombopag before and after surgery153 and also need further consideration for romiplostim. Regulatory Status FDA-approved indications: Nplate is a thrombopoietin receptor agonist indicated for the treatment of thrombocytopenia in: (1) 1. Alternatively, analysis of the pooled safety data from 14 trials (N=1059) that included pediatric (n=23) and adult (n=1036) patients revealed that three patients (ages not reported) developed neutralizing antibodies to romiplostim, but these did not cross-react with endogenous TPO. This medicine is to be given only by or under the direct supervision of your doctor. Primary persistent thrombocytopenia is most prevalent with a cord blood transplant. Learn about side effects, how it's given, cost, and more of Nplate (romiplostim). and transmitted securely. Wang YM, Krzyzanski W, Doshi S, Xiao JJ, Perez-Ruixo JJ, Chow AT. As reviewed by Kuter and Begley,7 TPO is synthesized primarily in the liver as a single 353amino acid precursor protein.
Nplate (romiplostim) Information | FDA Through this mechanism, romiplostim reduces the need for other treatments and decreases bleeding events in patients with thrombocytopenia. Eulenfeld R, Dittrich A, Khouri C, et al. Federal government websites often end in .gov or .mil. In turn, these functions may affect the outcome of TPO-MPL signaling in hematopoietic stem cells,11 areas in which TPO-RAs have unique and distinct effects.11 Along with increasing platelet production, TPO-RAs also appear to transiently extend their circulating life span, potentially via signaling through the AKT pathway and reducing sensitivity to apoptotic stimuli.21. We also summarize the clinical evidence supporting its use in ITP and other disorders that involve thrombocytopenia, including chemotherapy-induced thrombocytopenia, aplastic anemia, acute radiation syndrome, perisurgical thrombocytopenia, post-HSCT thrombocytopenia, and liver disease. Gernsheimer T, Stratton J, Ballem PJ, Slichter SJ. Romiplostim and eltrombopag induce platelet response after 1 to 2 weeks of treatment, whereas avatrombopag has a response onset of 3 to 5 days. Case reports letter, Successful antiviral therapy for hepatitis C virus-induced cirrhosis after an increase in the platelet count with romiplostim: two case reports, Myelodysplastic syndromes: diagnosis and treatment, Thrombocytopenia in patients with myelodysplastic syndromes: still an unsolved problem, Myelodysplastic syndromes current treatment algorithm 2018. Medscape. Mitchell WB, Pinheiro MP, Boulad N, et al. Preclinical activity of eltrombopag (SB-497115), an oral, nonpeptide thrombopoietin receptor agonist, Stem cell stimulation continues to pay off in aplastic anaemia. 2020 Sep;96(9):1125-1134. doi: 10.1080/09553002.2020.1787546. A retrospective, long-term, multicenter follow-up study of 121 adults with ITP who had been treated with TPO-RAs assessed factors associated with treatment-free responses. Current radiation countering medicinals within space vehicle's emergency medical kit # Drug type/ class ; Mechanism of action; Intended use ; Drug name ; Drug ; maker; Route/ dose ; 1. a. Anti-emetics. Kantarjian HM, Fenaux P, Sekeres MA, et al.
Romiplostim promotes platelet recovery in a mouse model of multicycle This is particularly relevant in the posttransplant setting when the risk of hemorrhagic events is often increased by diffuse endothelial damage. For example, romiplostim activates the extracellular domain of the TPO-R, whereas eltrombopag and avatrombopag activate the transmembrane portion of the TPO-R (Figure 4),),33 which could lead to different levels of activity of the TPO-R and hence different responses within the stem cell and megakaryocyte compartments. See cytokines page and romiplostim FDA drug label.
PDF Nplate (romiplostim) At week 9, platelet response was achieved in 10 of 33 patients (30%) and appeared to be dose dependent, with responses in seven of 10 who received romiplostim 10 g/kg and three of nine who received romiplostim 6 g/kg. A comparative prospective observational study of children and adults with immune thrombocytopenia: 2-year follow-up, Managing thrombocytopenia associated with cancer chemotherapy. Romiplostim: dose escalation from 110 g/kg weekly; 18 patients achieved platelet count 50 10, Bone marrow biopsies at 12 weeks and 1 year after the start of treatment did not show any increase in marrow fibrosis, Romiplostim appears to be effective in improving platelet count in patients with transfusion-dependent thrombocytopenia. Among patients in this retrospective study receiving only romiplostim (n=41) or eltrombopag (n=41), 95.1% in each group were not exposed to switching. It has been reported that the high-dosage administration of domestically approved pharmaceutical drugs, especially granulocyte colony-stimulating factor (G-CSF) and romiplostim (RP), is a rapid and appropriate medical treatment for preventing severe acute radiation syndrome (ARS) of victims exposed to lethal total-body irradiation (TBI). absorbed whole body radiation dose (i.e., level of radiation exposure) based on information from public health authorities, biodosimetry if available, or clinical findings such as time . Pharmacodynamics of romiplostim alone and in combination with pegfilgrastim on acute radiation-induced thrombocytopenia and neutropenia in non-human primates. Drug Des Devel Ther. J Clin Oncol. Acquired aplastic anemia is a clinical syndrome characterized by deficiency of red blood cells, neutrophils, monocytes, and platelets in the blood, as well as fatty replacement of the marrow with almost complete absence of hematopoietic precursor cells. Vehicle, romiplostim, and/or pegfilgrastim were administered subcutaneously beginning 24 h after TBI for 1-5 days.
It was estimated that nearly 10% of patients treated with chemotherapy experience clinically significant CIT during at least one cycle of their treatment.105 Current management for CIT includes platelet transfusions, which are reserved for patients with severe thrombocytopenia.104 Chemotherapy treatment delays and dose reductions are often used to manage CIT, which lead to reduced relative dose intensity and, consequently, reduced efficacy of the chemotherapy regimen.106,107 A recent study investigated the effects of the antifibrinolytic drug tranexamic acid in preventing therapy-induced thrombocytopenia in patients undergoing treatment for hematologic malignancies; however, early results indicate that prophylactic tranexamic acid had no effect on the incidence of bleeding.108 This suggests that a potential way to treat CIT is to increase platelet counts.
Romiplostim (Nplate) as an effective radiation countermeasure to Development of Romiplostim for Treatment of Primary Immune Thrombocytopenia From a Pharmacokinetic and Pharmacodynamic Perspective. Disclaimer, National Library of Medicine
Romiplostim (Nplate) as an Effective Radiation Countermeasure to Eltrombopag for the treatment of inherited thrombocytopenias: a Phase II clinical trial, Romiplostim for the management of pediatric immune thrombocytopenia: drug development and current practice, Atypical presentation of Wiskott Aldrich syndrome in an infant [abstract]. Herein, we present the results of an analysis in mice of romiplostim as a medical countermeasure to improve survival and PLT recovery following acute radiation.Materials and methods: Male and female C57BL/6J mice (11 - 12 weeks of age, n = 21/sex/group) were total body irradiated (TBI) with 6.8 Gy X-rays that reduces 30-day survival to 30% (LD70/30). Gerrits AJ, Leven EA, Frelinger AL 3rd, et al. The study was stopped because of the increase in blasts attributed to functional TPO-R on the cells. Although none of these indications have been approved yet in the United States, these studies highlight the versatility of romiplostim in thrombocytopenic conditions other than ITP. The use of animal models in radiation research allows for the simulation of the biological effects of exposure in humans. Romiplostim has also been examined in combination with granulocyte colony-stimulating factor and recombinant human erythropoietin in irradiated mice, which led to 100% survival at day 30.145 A study in a rhesus macaque model of acute radiation syndrome found that romiplostim alone or in combination with pegfilgrastim prevented severe thrombocytopenia and had other hematologic benefits.147 Rhesus macaques were given a uniform dose of 550 cGy 24 hours before administration of saline (control), romiplostim, pegfilgrastim, or a combination of both. Krzyzanski W, Sutjandra L, Perez-Ruixo JJ, Sloey B, Chow AT, Wang YM. Here, we review the structure, mechanism, pharmacokinetics, and pharmacodynamics of romiplostim. Home self-injections (available outside the US) may be an option for some patients and increase compliance, although some patients may prefer receiving treatment in an office by a healthcare professional. Whether treatment with romiplostim increases platelet counts and facilitates a bleeding-free window to allow spontaneous platelet recovery or in some way permanently increases the platelet count still needs to be assessed. The FDA's decision was based largely on NIAID-supported studies showing that romiplostim greatly increases survival in an animal model of radiation exposure. Zhao LP, Sicre De Fontbrune F, Contejean A, et al. Antigens from phagocytosed platelets are thought to be presented by the MHCII to TCRs, stimulating autoreactive T cells. Conversely, TPO binds to MPL receptors on circulating platelets in the blood when platelet levels are high. Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia, Thrombopoietin agonists for the treatment of thrombocytopenia in liver disease and hepatitis C. Castellote J, Girbau A, Arajol C, Xiol X. Romiplostim in chronic liver disease with severe thrombocytopenia undergoing an elective invasive procedure. immune thrombocytopenia, pharmacokinetics, pharmacodynamics, structure, thrombopoietin receptor agonist. Cwirla SE, Balasubramanian P, Duffin DJ, et al. 2020 Jan;96(1):155-166. doi: 10.1080/09553002.2019.1625488. Nichola Cooper has received honoraria for speaking engagements and participated in advisory boards with Amgen, Novartis, Principia, and Rigel; and has received support for clinical trials from Amgen, Novartis, Rigel, Principia, and UCB. Thrombopoietin receptor agonists for severe thrombocytopenia after allogeneic stem cell transplantation: experience of the Spanish Group of hematopoietic stem cell transplant. Such incidences are perceived as national security threats . However, much of the information may also apply to unapproved uses that are being studied. Xue E, Lawrence T, Gernsheimer TB, Milano F. Retrospective evaluation of the use of romiplostim after hematopoietic stem cell transplantation. Effects of tranexamic acid prophylaxis on bleeding outcomes in hematologic malignancy: the a-TREAT trial, Romiplostim promotes platelet recovery in a mouse model of multicycle chemotherapy-induced thrombocytopenia, Efficacy of romiplostim in the treatment of chemotherapy induced thrombocytopenia (CIT) in a patient with mantle cell lymphoma. Questo studio di fase II studia l'efficacia di romiplostim nell'aumentare la bassa conta piastrinica in pazienti con mieloma multiplo sottoposti a . Romiplostim or standard of care in patients with immune thrombocytopenia. 2022 Sep 25;11(10):1895. doi: 10.3390/antiox11101895. In particular, in severe aplastic anemia, for which eltrombopag has been licensed as upfront treatment in combination with standard immunosuppressive therapy, a recent study showed similar efficacy of romiplostim.18 The safety and efficacy of romiplostim has led to anecdotal use in both primary and secondary thrombocytopenia in the post-HSCT setting, where response to treatment eventually allows prevention of bleeding and differentiation of thrombocytopenia caused by concomitant post-HSCTspecific complications. Chemical structure of romiplostim.60 Romiplostim (molecular weight 60 kDa) is a peptibody composed of four identical thrombopoietin peptides of 14 amino acids each that are chemically coupled by glycine spacer domains to the carboxy-terminus of the Fc carrier domain. Further exploration of these mechanisms in the function of peptibodies is warranted.67. Romiplostim works by causing the cells in the bone marrow to produce more platelets. government site. Romiplostim for management of chemotherapy-induced thrombocytopenia, Thrombopoietin receptor agonists are effective in treating chemotherapy-induced thrombocytopenia in patients with gliomas undergoing myelotoxic treatment. There was a significant reduction in chemotherapy dose delay or dose decrease, as well as a decrease in platelet transfusions, with TPO-RAs, with no apparent increased risk of thrombosis.122 The primary question remains whether these important practical findings will translate into improved survival. Epub 2020 Jul 15. Myelosuppression is a bone marrow problem that can lead to a decrease in blood cell counts.
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