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Presentation Details
| REDUCTION IN CONCOMITANT THERAPY USE WITH RILZABRUTINIB AND SUSTAINED RESPONSE IN ADULTS WITH PERSISTENT/CHRONIC IMMUNE THROMBOCYTOPENIA (ITP) IN THE PHASE 3 LUNA3 LONG-TERM EXTENSION (LTE) PERIOD David J.Kuter1, Lei Zhang2, Waleed Ghanima3, Yoshitaka Miyakawa4, Yu Hu5, David Gómez-Almaguer6, Matias Cordoba7, Marek Wardęcki8, Larissa Mege9, Meredith C.Foster7, Ahmed Daak7, Howard A.Liebman10, Sandhya Panch11. 1Hematology Division, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.2Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Tianjin, China.3Østfold Hospital Trust, Grålum, Norway and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.4Department of Hematology, Saitama Medical University, Saitama, Japan.5Wuhan Xie'he Hospital, Wuhan, China.6Hospital Universitario Dr.José Eleuterio González, Monterrey, Mexico.7Sanofi, Cambridge, MA, USA.8Sanofi, Warsaw, Poland.9Sanofi, Lyon, France.10University of Southern California, Los Angeles, CA, USA.11Fred Hutch, Fred Hutch, USA |
Abstract
Background: Rilzabrutinib is an oral, reversible, covalent Bruton tyrosine kinase inhibitor that acts through multi-immune modulation in ITP. The phase 3 LUNA3 study (NCT04562766, 2020-002063-60) of rilzabrutinib in adults with persistent/chronic ITP demonstrated rapid and durable platelet response, improved physical fatigue and bleeding scores, and favorable safety in the double-blind (DB), open-label (OL), and interim analyses of the LTE periods. Objectives: Provide longer LTE follow-up focusing on changes in concomitant corticosteroids and/or thrombopoietin receptor agonists (TPO-RA). Methods: Patients with persistent/chronic ITP were eligible for LTE with response during the last 8 weeks of the OL period (platelet count ≥50×109/L or ≥30×109/L and ≥doubled from baseline at ≥50% of visits without rescue therapy). LTE patients received oral rilzabrutinib 400 mg bid until loss of response on 2 consecutive visits or for safety reasons. Stable baseline doses of concomitant corticosteroids and/or TPO-RA, dose reduction/discontinuation, and rescue therapy were allowed. Results: Overall, 69/180 (38%) OL patients entered the LTE and, as of April 1, 2025, 43/69 (62%) had completed ≥12 months of LTE follow-up. Median platelet count at LTE entry was 113×109/L (range, 20-877×109/L) and ranged from 83-168×109/L through 33 months of LTE. During the first 12 months of LTE, patients had platelet counts ≥50×109/L or between 30-50×109/L and ≥doubled from baseline for an average of 88% (SD, 24%) of visits. Of those receiving rilzabrutinib monotherapy (n=22, 32%) and with concomitant corticosteroids and/or TPO-RA (n=47, 68%) at DB baseline, respective median platelet counts were 78×109/L (range, 20-371×109/L) and 115×109/L (range, 28-877×109/L) at LTE entry, and ranged from 78-270×109/L and 90-160×109/L through 33 months of LTE (Figure). Twenty LTE patients discontinued concomitant corticosteroids and/or TPO-RA prior to or during the LTE. Ten LTE patients discontinued corticosteroids (switched to rilzabrutinib monotherapy), 2 reduced corticosteroids ≥50% from DB baseline, and 6 reduced corticosteroid dose to <5 mg (prednisone qd). Median platelet counts before and after corticosteroid discontinuation at last available LTE visit were 148×109/L (range, 19-722×109/L) and 178×109/L (range, 3-405×109/L), respectively. Of 11 patients on concomitant TPO-RA or corticosteroid/TPO-RA at DB baseline, 5 discontinued TPO-RA before entering LTE (romiplostim: n=1; avatrombopag: n=2; eltrombopag: n=2) and 1 during the LTE (eltrombopag). Fourteen of 20 (70%) patients discontinuing corticosteroids and/or TPO-RA were able to maintain platelet counts >100×109/L during most visits after discontinuation; 3 required rescue medication after discontinuing concomitant medication. Improved physical fatigue and bleeding scores were generally maintained during LTE. In the LTE, 14 (20%) patients received rescue medication. Thirteen (19%) patients had treatment-related adverse events (AEs); most common were nausea (7%), diarrhea (4%), and upper abdominal pain (3%). Two patients (3%) had treatment-related grade ≥2 infection; both recovered without interrupting rilzabrutinib. No treatment-related grade ≥2 bleeding events, serious AEs, or deaths occurred. Conclusions: Rilzabrutinib continued to demonstrate favorable safety, sustained platelet responses and improved ITP-related symptoms during the LTE period. Most LTE patients receiving concomitant corticosteroids and/or TPO-RA were able to discontinue/reduce use while maintaining platelet counts. These results further underscore the disease-modifying potential of multi-immune modulation with rilzabrutinib in patients with ITP.
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No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author.