Safety and efficacy of rilzabrutinib vs placebo in adults with immune thrombocytopenia: the phase 3 LUNA3 study
Abstract
Abstract Rilzabrutinib is a covalent, reversible Bruton tyrosine kinase inhibitor targeting multiple immune thrombocytopenia (ITP)-related mechanisms. The phase 3 LUNA3 study in previously treated adults with persistent/chronic ITP evaluated oral rilzabrutinib 400 mg twice daily (n = 133) vs placebo (n = 69) for 24 weeks. At baseline overall, median age was 47 years, 63% female, 7.7 year median ITP duration, and 28% prior splenectomy. Overall (N = 202), 85 (64%) rilzabrutinib and 22 (32%) placebo patients achieved platelet response (≥50 × 109/L or 30 × 109/L to <50 × 109/L and doubled from baseline) during the first 12 weeks and were eligible to continue. The primary end point, durable platelet response (platelet count ≥50 × 109/L for ≥two-thirds of ≥8 of the last 12 of 24 weeks without rescue therapy), was observed in 31 (23%) rilzabrutinib vs 0 placebo patients (P < .0001). All secondary efficacy end points were significantly superior for rilzabrutinib (P < .05). Median time to first platelet response was 15 days in rilzabrutinib responders. Rilzabrutinib significantly reduced rescue therapy use by 52% (P = .0007) and improved week 25 bleeding scores (P = .0006). Improved physical fatigue was sustained from week 13 (P = .01) through 25 (P = .0003). Treatment-related adverse events were mainly grade 1/2. One rilzabrutinib patient with multiple risk factors had serious treatment-related grade 3 peripheral embolism (lower left leg), and another died from unrelated pneumonia. Rilzabrutinib in patients who failed multiple previous ITP therapies showed rapid and durable platelet response, reduced rescue medication and bleeding, improved physical fatigue, and favorable safety. Trial registration: www.clinicaltrials.gov (#NCT04562766) and www.clinicaltrialsregister.eu (#2020-002063-60).
Article Details
Authors (32)
David J. Kuter
Hematology Division, Massachusetts General Hospital, Boston
Waleed Ghanima
6Østfold Hospital Trust, Kalnes, Norway
Nichola Cooper
4Imperial College Healthcare NHS Trust, Haematology, London, United Kingdom
Howard A. Liebman
4Department of Hematology, University of Southern California, Los Angeles, CA
Lei Zhang
Yu Hu
Yoshitaka Miyakawa
3Department of Hematology, Saitama Medical University, Saitama, Japan
Wojciech Homenda
14Regional Hospital of Slupsk and Institute of Health Sciences, Pomeranian University of Slupsk, Slupsk, Poland
Luisa Elena Morales Galindo
9Department of Hematology, IC La Serena Research SpA, La Serena, Chile
Ana Lisa Basquiera
10Department of Hematology, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina
Chuen Wen Tan
11Department of Hematology, Singapore General Hospital, Singapore, Singapore
Güray Saydam
9Ege University Medical Faculty Hospital, Department of Internal Diseases, Division of Hematology, Izmir, Türkiye
Marie Luise Hütter-Krönke
5Charité - Universitätsmedizin, Department of Hematology, Oncology and Tumor Immunology, Berlin, Germany
Chatree Chai-adisaksopha
David Gomez-Almaguer
1Hospital Universitario Dr. Jose Eleuterio Gonzalez, Hematologia, monterrey, Mexico
Huy Tran
2Baylor College of Medicine/Texas Children's Hospital, Houston, United States
Ho-jin Shin
Pusan National University Hospital, Busan, Korea, Republic of
Ademar Dantas da Cunha Junior
18Department of Hematology, Hospital do Cancer de Cascavel, Uniao Oeste Paranaense de Estudos e Combate ao Cancer, Cascavel, Brazil
Zsolt Lazar
3Petz Aladár County Teaching Hospital, Győr, Hungary
Cristina Pascual Izquierdo
20Department of Hematology, Hospital General Univdersitario Gregorio Marañon, Instituto de Investigación Gregorio Marañon, Madrid, Spain
Ilya Kirgner
21Department of Hematology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv Sourasky Medical Center, Tel Aviv, Israel
Elisa Lucchini
26Unit of Hematology, Dipartimento di Medicina Specialistica, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Italy
Ganna Kuzmina
23Department of Hematology, Municipal Enterprise Kryvyi Rih City Clinical Hospital No. 2 of Kryvyi Rih City Council, SI Dnipropetrovsk Medical Academy under the Ministry of Health of Ukraine, Kryvyi Rih, Ukraine
Michael Fillitz
14Hanusch Krankenhaus, Department of Internal Medicine, Vienna, Austria
Sylvain Audia
Minakshi Taparia
25University of Alberta, Edmonton, Canada
Matias Cordoba
16Sanofi, Cambridge, United States
Remco Diab
28Sanofi, Zug, Switzerland
Mengjie Yao
29Sanofi, Bridgewater, NJ
Imene Gouia
9Sanofi, Gentilly, France
Michelle Lee
Ahmed Daak
16Sanofi, Cambridge, United States