Efficacy and Safety Results With Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, in Patients With Immune Thrombocytopenia: Phase 2 Part B Study
- Author(s)
- Cooper, N; Jansen, AJG; Bird, R; Mayer, J; Sholzberg, M; Tarantino, MD; Garg, M; Ypma, PF; McDonald, V; Percy, C; Košťál, M; Goncalves, I; Bogdanov, LH; Gernsheimer, TB; Diab, R; Yao, M; Daak, A; Kuter, DJ;
- Details
- Publication Year 2025-03,Volume 100,Issue #3,Page 439-449
- Journal Title
- American Journal of Hematology
- Publication Type
- Research article
- Abstract
- Current treatments for persistent or chronic immune thrombocytopenia (ITP) are limited by inadequate response, toxicity, and impaired quality of life. The Bruton tyrosine kinase inhibitor rilzabrutinib was evaluated to further characterize safety and durability of platelet response. LUNA2 Part B is a multicenter, phase 1/2 study in adults with ITP (≥ 3 months duration, platelet count < 30 × 10(9)/L) who failed ≥ 1 ITP therapy (NCT03395210, EudraCT 2017-004012-19). Oral rilzabrutinib 400 mg bid was given over 24 weeks, with optional long-term extension (LTE). Primary endpoints were safety and platelet counts ≥ 50 × 10(9)/L on ≥ 8 of the last 12 weeks of main treatment without rescue medication. From 22 March2018 to 31 January2023, 26 patients were enrolled. Patients had baseline median platelet count 13 × 10(9)/L, ITP duration 10.3 years, and six prior ITP therapies (46% splenectomized). Nine (35%) patients achieved the primary endpoint. Platelet counts ≥ 50 × 10(9)/L or ≥ 30 × 10(9)/L and doubling from baseline without rescue therapy were sustained for a mean 9.3 weeks. 11 (42%) LTE-eligible patients were ongoing with median LTE platelet > 80 × 10(9)/L. Three (12%) patients received rescue medication during main treatment, none in LTE. Clinically meaningful improvements were observed in fatigue and women's health. With a median treatment duration of 167 days (main treatment), 16 (62%) patients had ≥ 1 treatment-related adverse event (AE), mainly grade 1, including diarrhea (35%), headache (23%), and nausea (15%). There was no treatment-related grade ≥ 2 bleeding/thrombotic events/infections, serious AE, or death. Rilzabrutinib continues to demonstrate durable platelet responses with favorable safety profile in previously treated ITP patients. Trial Registration: NCT03395210, EudraCT 2017-004012-19.
- Publisher
- Wiley
- Keywords
- Humans; Middle Aged; *Purpura, Thrombocytopenic, Idiopathic/drug therapy; Female; Male; Aged; Adult; *Agammaglobulinaemia Tyrosine Kinase/antagonists & inhibitors; *Protein Kinase Inhibitors/adverse effects/therapeutic use/administration &; dosage; Platelet Count; Administration, Oral; Pyrimidines/administration & dosage/adverse effects/therapeutic use; Treatment Outcome; Pyrazoles/therapeutic use/adverse effects/administration & dosage; Aged, 80 and over; Tyrosine Kinase Inhibitors; adults; immune thrombocytopenia; platelets; quality of life; response
- Department(s)
- Haematology
- Publisher's Version
- https://doi.org/10.1002/ajh.27539
- Open Access at Publisher's Site
https://doi.org/10.1002/ajh.27539- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-02-11 06:50:37
Last Modified: 2025-02-11 06:50:48