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3948 Investigating the Effectiveness and Safety of Combining Thrombopoietin Receptor Agonist and Immunosuppressant Drugs for Patients with Multirefractory Immune Thrombocytopenia after Second-Line Monotherapy Treatments

Program: Oral and Poster Abstracts
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Autoimmune disorders, Combination therapy, Diseases, Immune Disorders, Treatment Considerations
Monday, December 9, 2024, 6:00 PM-8:00 PM

Maria Eva Mingot-Castellano, MD, PhD1*, Patricia Alcalde Mellado, MD1*, Laura Entrena Ureña, MD2*, Maria Cristina Pascual Izquierdo, MD, PhD3*, Denis Zafra4*, Mariana Canaro Hinryk, MD5*, Jose Maria Bastida, MD, PhD6*, Silvia Bernat Bernat7*, Daniel Martinez Carballeira8*, Isabel Caparros Miranda9*, Amalia Cuesta Garcia10*, Sunil Lakhwani11*, Blanca Sanchez Gonzalez12*, Marta Canet Maldonado13*, Maria Carmen Gómez del Castillo Solano14*, Marta García Culebra1*, Beatriz Chiclana Rodriguez1*, Manuel Fernanadez-Villalobos15*, Paula Sanchez Llorca16*, Lola Piquer Monsonis17*, Carlos Puerta Vazquez18*, Rocio Perez Montes10*, Francesc Garcia-Pallarols, BSc19*, David Valcarcel, MD, PhD20 and Begoña Pedrote Amador, MD1*

1Hospital Universitario Virgen del Rocío, Instituto de Biomedicina de Sevilla. Universidad de Sevilla, Sevilla, Spain
2Hospital Universitario Virgen de las Nieves, Granada, Spain
3Servicio de Hematología, Hospital Universitario Gregorio Marañón, Instituto de Investigación Gregorio Marañón, Madrid, Madrid, Spain
4Hospital Universitario 12 De Octubre, Madrid, Spain
5Hematology Department., Hospital Universitario Son Espases, IdISBa., Palma, Spain
6Hematology Department, Hospital Clínico Universitario de Salamanca-IBSAL, Salamanca, Spain
7Hospital Universitario de La Plana, Villarreal, Castellón., Villarreal, CastellóN, ESP
8Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain, Oviedo, Spain
9Hospital Universitario Virgen de la Victoria, Málaga., Malaga, Spain
10Hospital de Sierrallana, Torrelavega, Spain
11Hospital Universitario de Canarias, La Laguna, Spain
12Hematology Department, Hospital del Mar, Barcelona, Spain
13Hospital Universitari Mútua Terrassa, Terrassa, Barcelona., Barcelona, Spain
14Complexo Hospitalario Universitario A Coruña, La Coruña, Spain
15Hospital General Universitario Gregorio Marañon, Madrid, Madrid, Spain
16Hospital 12 de octubre, Madrid, Spain
17Hospital Universitario Son Espases, Mallorca, Spain
18Complejo Asistencial Universitario de Salamanca (CAUSA) - IBSAL, Salamanca, Salamanca, Spain
19Hospital del Mar, Barcelona, Spain
20Department of Hematology and Oncology, Hospital Universitario Vall d'Hebron, Barcelona, Spain

Introduction

Combining thrombopoietin receptor agonists (TPO-RAs) with immunosuppressant drugs (ISTs) may be beneficial for patients with multi-refractory immune thrombocytopenia (mrITP). There is limited evidence based on small series and clinical cases, with the longest series involving 39 patients from the French ITP registry. Our objective is to describe the types of combinations used, the rate and type of response, and the safety profile of combined TPO-RA and IST treatment in mrITP in our setting.

Material and Methods

This is a multicenter, observational and retrospective study endorsed by the Spanish ITP group (GEPTI). Patients with ITP older than 18 years old, refractory to three or more lines of treatment in monotherapy, who received combined TPO-RA and IST therapy between January 2021 and December 2023 were included. The response criteria used were The International Working Group standards. Statistical analysis was applied with 95% confidence interval, 5% significance level, using chi-square or ANOVA for group comparisons.

Results

A total of 113 patients were included in this study, with 130 different combinations treatments indicated. The median age was 53 years (IQR: 34-65), 47.6% were male and 35.4% had two or more vascular risk factors. Regarding the phase of ITP, 65% of cases were chronic ITP (cITP). The median number of previous treatment lines was 4 (IQR, 3-7). The TPO-RAs used included eltrombopag (ELT) in 44% of cases, romiplostim (ROM) in 36%, and avatrombopag (AVA) in 20%. The most commonly used ISTs were prednisone (41%), azathioprine/mycophenolate (20.3%), and dexamethasone (19%). The median time from ITP diagnosis to combination therapy was 31 months (IQR: 6.8-103). The overall response rate was 75.4% (62.3% complete responses), which was higher in those treated with ROM (84.1% vs. 69.2%, p = 0.012), with no differences according to IST. The median time to response was 15 days (IQR: 7-60). The response time was shorter in those treated with dexamethasone (median 6 days vs. 15 days, p = 0.048), with no difference according to TPO-RA. The median weekly dose of TPO-RA at the time of response was ELT 525mg (IQR:350-525), ROM 531mcg (IQR: 352.5-772.5), and AVA 280mg (IQR: 280-280).

With a median follow-up of 120 weeks (IQR: 69.5-170), 22.4% of subjects required rescue treatment on at least two occasions, with 14% needing hospitalization. 73% of patients maintained response, and 60% of responses were complete. Treatment was discontinued in 12 patients while maintaining the response (responsible use of medications in 7 patients and eltrombopag in 5, combined with prednisone or azathioprine). In terms of safety, 14% of the people treated with corticosteroids needed antidiabetic treatment. There were three thrombotic events reported (1 venous sinus thrombosis and 2 ischemic events. Three patients were hospitalized for SARS-CoV-2 pneumonia. Additionally, 16% of the subjects received antibiotic prevention, and 19% were given osteopenia prevention. Five patients experienced digestive issues with ELT treatment. Among those treated with fostamatinib, one case of hypertension and two cases of grade 2 digestive issues were reported.

Conclusion

The combination of TPO-RAs and immunosuppressants has been effective and safe in treating multi-refractory ITP in our experience. However, more clinical trials are needed to validate its use.

Disclosures: Canaro Hinryk: Novo Nordisk, Takeda, Roche, Pfizer, Octapharma, Amgen, Novartis, CSL Behring and Sobi: Honoraria; Novo Nordisk, Takeda, Roche, Pfizer, Octapharma, Amgen, Novartis, CSL Behring and Sobi: Speakers Bureau. Valcarcel: TAKEDA: Consultancy, Honoraria, Speakers Bureau; Bristol Myers Squibb/Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Honoraria, Speakers Bureau; Astellas: Consultancy, Honoraria; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Agios: Honoraria, Other: Meeting and travel accommodation, Speakers Bureau; MSD: Consultancy, Honoraria, Speakers Bureau; Gebro: Honoraria, Speakers Bureau; Sanofi: Consultancy, Honoraria, Other: Meeting and travel accommodation, Speakers Bureau; Servier: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Jazz Pharmaceuticials: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; Janssen: Honoraria, Speakers Bureau; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; SOBI: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Meeting and travel accommodation, Speakers Bureau; AbbVie: Consultancy, Other: Meeting and travel accommodation.

*signifies non-member of ASH