Usefulness of Eltrombopag in Secondary ITP Patients in Clinical Practice
Authors: González-López Tomás José , Alvarez-Roman María Teresa , Pascual Cristina , Sánchez-González Blanca , Fernández-Fuentes Fernando , Pérez-Rus Gloria , Hernández-Rivas José Angel , Bernat Silvia , Cortés Montserrat , Bastida José María , Martínez-Robles Violeta , Fernández-Rodríguez Angeles , Olivera Pavel , Bolaños Estefanía , Alonso Rafael , Entrena Laura , Gómez-Nuñez Marta , Bermejo Nuria , Martínez-Badas María Paz , Peñarrubia María Jesús , Alonso Arancha , Soto Inmaculada , Yera Cobo María , Casaus Alberto , Caparrós Isabel , Perera María , Jiménez Bárcenas Reyes , Heras Cecilia , Calbacho María , Tenorio Maria , Luaña Armando , Lopez-Ansoar Elsa , Hermida Gerardo , García-Frade Javier , González-Porras José Ramón , Sanz Miguel A. 
Published: October 2019

Background: Eltrombopag is an oral thrombopoietin receptor agonist (TPO-RA) drug approved in primary chronic ITP. Lack of clinical trials in secondary ITP avoids a clear demonstration of its potential in terms of safety and efficacy on secondary ITP.

Aims: To evaluate the efficacy and safety of eltrombopag in secondary ITP patients in daily clinical practice in Spain.

Methods: Ninety-eight secondary ITP patients (aged 18 years or more) from 30 Spanish centers, treated with eltrombopag and included in the Spanish Eltrombopag Registry were retrospectively evaluated. Our study was performed in accordance with the standards of the Helsinki declaration and approved by the Hospital Universitario de Burgos Ethics Committee.

Results:

Our case series included 98 patients we allocated to four categories: immune disorders (n=47), infections (n=23), lymphoproliferative disorders (n=20), and neoplasms (n=8).

The median age of the cohort was 62 (IQR, 40-71) years with 38 men and 60 women. At diagnosis, 34 patients had a Charlson Comorbidity Index score of 2 or more. Median time from ITP diagnosis to eltrombopag initiation was 13 (IQR, 2-66) months. Median number of therapies against thrombocytopenia before eltrombopag was 2 (IQR, 1-3), including rituximab (24), splenectomy (18) and romiplostim (13). Median platelet count when treatment started was 15 x 109/L (IQR, 5-43 x 109/L). Meanwhile, 44 patients had bleeding symptoms. Concomitant therapy was administered to 55 ITP (corticoids in 33) (Table I).

Whole cohort eltrombopag response rate was 59% of responses (R; platelet count ≥30 x109/L and at least 2-fold increase the baseline count and absence of bleeding) with 52% of complete responses (CR; platelet count >100 x 109/L). Regarding the disease associated to ITP we observed high response rates in immune disorders and infection groups (67% of R, 76 % of R, respectively). Nevertheless, in lymphoproliferative disorders and neoplastic groups efficacy rates were much lower (36 % of R, 37 % of R respectively). The proportion of patients achieving platelet response was quite similar regardless the other studied parameters: age, sex, concomitant treatment, bleeding and platelet count at start of eltrombopag treatment.

30 adverse events were reported with eltrombopag, being 18 of them grade 3-4. 14 deaths were observed but only two were caused by bleeding. The remaining causes of death were: 4 because of bacterial sepsis and another 4 due to progression of basal disease. 2 secondary neoplasms, 1 aspergillosis and one death due to a non-treated severe anemia were also reported (Table II).

Conclusion:

The use of eltrombopag for treating secondary ITP is effective and safe. To point out, its efficacy in lymphoproliferative disorders and in neoplasm-associated ITP is lower than in benign diseases.

Certainly, more studies are needed to confirm usefulness of TPO-RAs in secondary ITP cases.

Table 1. Patient characteristics Variable Total(n = 98) Type of disease, n Immune disorders  SLE 13  Evans Syndrome 8  Antiphospholipid Syndrome 6  Sjögren Syndrome 5  Rheumatoid Arthritis 3  Immunodeficiencies 3  Autoimmune Hepatitis 2  Primary Biliary Cirrhosis 2  Psoriatic arthritis 1  Evans Syndrome-Immunodeficiencies 1  Evans Syndrome-HCV 1  Graves-Basedow disease 1  Inflammatory Bowel disease 1 Lymphoproliferative disorders  Lymphoproliferative diseases 16  HCV-Lymphoma 3  HIV-Lymphoma 1 Infections  Hepatitis C Virus 16  HIV 5  HCV-HIV 2 Neoplasms  Myeloid Neoplasms 8 Age, years, median [Q1;Q3] 62[40;71] Men/Women n 38/60 Bleeding at start of eltrombopag treatment, n 44 Concomitant treatment, n 55  Corticoids 33  Immunoglobulins 6  Corticoids and Immunoglobulins 7

Table 2. Adverse events with Eltrombopag Variable n Total, n 30 Serious Adverse Events (Grade 3-4), n 18  Progression of basal disease 4  Severe Bacterial Infections 3  Deep venous thrombosis 3  Stroke 2  Medullary fibrosis 2  Severe Bleeding 1  Aspergillosis 1  Pulmonary Embolism 1  Secondary neoplasms 1  Acute Pancreatitis 1  Acute Myocardial Infarction 1 Deaths, n 14  Bacterial Infections 4  Progression of basal disease 4  Secondary neoplasms 2  Severe Bleeding 2  Aspergillosis 1   Severe Anemia due to negative of patient to transfusion 1

Disclosures

Off Label Use: We describe the possibility of using eltrombopag, an oral thrombopoietin receptor analog, for secondary ITP patients..