Thrombopoietin-Receptor Agonists the Mexican Experience: Romiplostim in 53 Non-Immune Thrombocytopenia Patients
Authors: Rodriguez-Mejorada Margarita , Marfil-Rivera Luis Javier , Rodriguez-Carrillo Jose 
Published: October 2019

Abstract
Abstract 4650
Immune thrombocytopenic purpura (ITP) is a well characterized disease, the annual incidence is 1 per 10,000 persons and evidence-based practice guidelines are now available. Secondary thrombocytopenia (STHR) associated with chemotherapy, bone marrow failure or malignant limphoproliferative diseases involving bone marrow are usually treated with platelet transfusion based on the WHO scale. However serious or even life-threatening complications are related with this procedure (alloinmunization,TRALI,virus, prions). Romiplostim (Romi), a new thrombopoietin receptor agonist (TPO-RA), is a peptibody that consists of two sections, one Fc domain (antibody) which lengthens half-life and one peptide domain which binds to thrombopoietin receptor. FDA approved Romi, in August 22, 2008 for patients with chronic ITP who have had an insufficient response to corticosteroids, IVIgG, or splenectomy. Clinical evidence supports the use of Romi, in severe STHR different from ITP. The Danish experience (Platelets 2012; 23(6):423-9), 4 of each 10 ptes treated with TPO-RA are not ITP. Mexican law prohibits economic remuneration for blood donation so donors are frequently insufficient to support patients with STHR during chemotherapy. Since the approval of Romi in Mexico (October 2010), we explore this new TPO-RA in non-immune STHR associated with different severe diseases; to assure a safe level of platelets without transfusion and preventing complications associated to this practice.

Material and Methods:
From October 2010 to July 2012 over 400 patients have received Romi in Mexico. We report here results in 53 patients with thrombocytopenia associated to different diseases. 27 female and 26 male with platelet count <30×109/L, high risk of bleeding regardless the cause of thrombocytopenia, age range 2 – 87 years, received Romi subcutaneously once a week until platelet count >50×109/L. Time for response and side effects were monitored.

Results:
27/26 (female/male) patients, age range 2–87 years, main diseases were: liver cirrhosis, myelodysplasia, bone marrow suppression post-chemo, bone marrow transplant, viral infections, systemic diseases associated with severe STHR. The initial average platelet count was 31 x109/L and 109 x109/L at final count, average dose of Romi was 4.3μg/k/wk. Median time to response was 7 days (range 7–30) with an average 6 doses per patient. 5 patients developed thrombocytosis with no clinical complications, 3 patients reported fatigue. None of them complained from subcutaneous administration.

Conclusions:
We are not certain that this is true for all patients, is an estimate that in Mexico, 6 of each 10 pts treated with Romi, are non ITP. Indications “out of label”, but favorable response justifies its use (Danish report 4/10). Life-threatening complications were resolved, chemotherapy was not delayed, we thought that the effect of Romi may reduce days of hospitalization and improve quality of life. Number of doses/weeks to achieve a “safe” platelet count varies according the main disease. Romiplostim induced fast response with minimum side effects, in some patients with non ITP.

Disclosures:
Off Label Use: Romiplostim used to revert life-threatening thrombocytopenia secondary to diseases different from ITP.