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3766 Efficacy and Safety of Tyrosine Kinase Inhibitors in the Treatment of Relapsed/Refractory Immune Thrombocytopenia

Program: Oral and Poster Abstracts
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Poster III
Hematology Disease Topics & Pathways:
Bleeding and Clotting, Biological therapies, Diseases, thrombocytopenias, Therapies, Immunotherapy, Adverse Events
Monday, December 12, 2022, 6:00 PM-8:00 PM

Muhammad Ashar Ali, MBBS1, Memoona Saeed2*, A. Supraja, MS Orthopedics3*, Maha Zafar4*, Ashish Nepal, MBBS5*, Muhammad Suleman6*, Rooma Habib, MBBS7*, Sana Rashid8*, Sumaiya Asfund9*, Muhammad Abdul Basit10*, Hafsa Zahoor11*, Sviatoslav Kosach12*, Aqsa Anwar13* and Wajeeha Aiman, MD14,15*

1Prime Health Care Consortium at Saint Clare's and Saint Mary's Hospital, Denville, NJ
2King Edward Medical University, Lahore, Pakistan
3NTRUHS, Vijayawada, Andhra Pradesh, India
4Arkansas College of Osteopathic Medicine Mercy Program, Fort Smith, AR
5University Hospitals Sussex NHS Foundation Trust, Brighton, United Kingdom
6Islamic International Medical College, Rawalpindi, Pakistan
7Dr Nikhil Gupta Medicine Professional Corporation NGMPC, Scarborough, ON, Canada
8Baqai Medical University, Karachi, Pakistan
9Jinnah Sindh Medical University, Karachi, Pakistan
10Services Institute of Medical Sciences, Lahore, Pakistan
11BronxCare Health System, Bronx, NY
12United HealthCare Global, Grat Britain, Ukraine
13Ameer Ud Din Medical College, Lahore, Pakistan
14Nishtar Medical University, Multan, Pakistan
15Internal Medicine, Saint Michael's Medical Center, Newark, NJ


Immune thrombocytopenia (ITP) is characterized by immune-mediated impairment of platelet production or platelet destruction leading platelet count of <100x103/mm3. First-line therapy of ITP includes IV immunoglobulin, steroids, and anti-D. However, long-term durable responses to these therapies are uncommon. Fc receptors on splenic phagocytes signal via spleen tyrosine kinases (Syk). Bruton tyrosine kinase (BTK) plays a crucial role in B-cell maturation and Fcy receptor-mediated phagocyte function. Therefore, inhibiting SyK or BTKIs can reduce macrophage activation leading to ITP. In this review, we assessed the efficacy and safety of BTKIs in the treatment of relapsed/refractory ITP.


We followed PRISMA guidelines to conduct this systematic review. A literature search was performed on PubMed, Web of Science, Embase (Ovid), and clinicaltrials.gov. with mesh terms, “Immune thrombocytopenia” and “tyrosine kinase” from the inception of data till 07/01/2022. We screened 474 articles and included three randomized clinical trials (RCTs, N=195) and one non-RCT (N=60) in this review. In the included clinical studies, stable response (SR) was platelets ≥50000/ micro L on ≥4 of 6 biweekly visits, modified stable response (MSR) was ≥2 consecutive platelet counts, separated by at least 5 days of ≥50,000 per micro L and the overall response (OR) was ≥1 platelet count of ≥50 000/micro L within the first 12 weeks on treatment.


In 4 clinical trials (N=255), the range of age of relapsed/refractory TKI participants was 18 to 88. 135 patients were treated with Syk inhibitors, 60 with BTK inhibitors, and 60 with placebo. In two clinical trials (N=135), SR and OR were reported in 18/101 (17.8%) and 43/101 (42.5%) patients, respectively in patients treated with fostamatinib versus SR and OR in 1/49 (2%) and 7/49 (14%), respectively in patients treated with placebo. In a clinical trial by Yang et al. (N=45), SR and OR were reported in 5/16 (31%) and 11/16 (68.8%) patients, respectively treated with HMPL-523 (Syk inhibitor) versus SR and OR in 1/11 (9%) patients treated with placebo. In a clinical trial by Kuter et al. (N=60), SR and MSR were reported in 17/60 (28%) and 24/60 (40%) patients, respectively treated with rilzabrutinib. Table 1.

Diarrhea, hypertension, dizziness, and neutropenia were serious side effects reported with fostamatinib leading to dose reduction in 9% of the patients. There were no dose-limiting adverse events reported with rilzabrutinib and HMPL-523. Table 1.


Syk inhibitors (fostamatinib and HMPL-523) and oral BTK inhibitor (rilzabrutinib) were effective and well tolerated by most of the patients with relapsed/refractory ITP. Rilzabrutinib and HMPL-523 had no dose-limiting side effects. A randomized phase III clinical trial (NCT04562766) is in progress to assess the efficacy and safety of rilzabrutinib. More trials are in progress to assess the efficacy and safety of novel TKIs like baricitinib, orelabrutinib, and zanubrutinib. Table 2.

Disclosures: No relevant conflicts of interest to declare.

*signifies non-member of ASH