-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

690 The Effects of Rilzabrutinib, an Oral Bruton Tyrosine Kinase Inhibitor, on Bleeding Symptoms and Health-Related Quality of Life in Patients with Immune Thrombocytopenia

Program: Oral and Poster Abstracts
Type: Oral
Session: 311. Disorders of Platelet Number or Function: Clinical and Epidemiological: Innovative Treatments for Immune Thrombocytopenia
Hematology Disease Topics & Pathways:
Bleeding and Clotting, bleeding disorders, Research, platelet disorders, Clinical Research, health outcomes research, thrombocytopenias, Diseases
Monday, December 11, 2023: 11:30 AM

Michael D. Tarantino, MD1, A.J. Gerard Jansen, MD2, Nichola Cooper, MD3,4*, Imene Gouia, PharmD, MSc Health Economics5*, Mengjie Yao6*, Ahmed Abd Almalik Daak, MD, PhD, MSc, DPM/MFPM7 and David J Kuter, MD, DPhil8

1The Bleeding and Clotting Disorders Institute, University of Illinois College of Medicine-Peoria, Peoria, IL
2Erasmus MC, University Medical Center, Rotterdam, Netherlands
3Centre for Haematology, Department of Immunology and Inflammation, Imperial College London, London, United Kingdom
4Hammersmith Hospital, London, United Kingdom
5Sanofi, Gentilly, France
6Sanofi, Bridgewater, NJ
7Sanofi, Cambridge, MA
8Massachusetts General Hospital, Harvard Medical School, Boston, MA

Introduction: Patients with immune thrombocytopenia (ITP) have a high incidence of comorbid conditions, elevated risk for bleeding and thrombosis, and reduced health-related quality of life (HRQoL). Rilzabrutinib is a potent oral, reversible inhibitor of Bruton tyrosine kinase with the potential to modulate multiple immunological pathways. In part A of a phase 1/2 study (LUNA 2) of ITP patients, rilzabrutinib treatment led to rapid and durable platelet responses with a favorable safety profile. This abstract reports the effects of rilzabrutinib on bleeding and HRQoL on patients in part B of the LUNA 2 study.

Methods: The multicenter, open-label, phase 1/2, part B study evaluated the efficacy and safety of rilzabrutinib 400 mg BID in relapsed ITP (NCT03395210). Adults aged 18-80 y were eligible with ≥2 baseline platelet counts <30x109/L no less than 7 days apart in the 15 days before the first dose. Eligible patients were required to have a past response (achievement of platelet count ≥50x109/L) to intravenous immunoglobulin (IVIg)/anti-D or corticosteroid (CS) that was not sustained, and have failed ≥1 other ITP therapy (not IVIg or CS). Stable doses of concomitant CS/thrombopoietin receptor agonists (TPO-RA) were allowed with rilzabrutinib. The primary endpoints were safety and durable platelet response defined as platelet counts ≥50x109/L on ≥8 of the last 12 weeks of rilzabrutinib without rescue medication. Change from baseline in the ITP Bleeding Scale (IBLS) score (0 none to 2 marked bleeding) was a secondary endpoint to assess bleeding across 9 anatomical sites (8 for male/postmenopausal women). An exploratory HRQoL endpoint evaluated the EuroQol-5 Dimensions 5-Level (EQ-5D-5L) + Visual Analog Scale (EQ-VAS) and ITP Patient Assessment Questionnaire (ITP-PAQ; scores 0 worst to 100 best HRQoL).

Results: For 26 enrolled patients with data cut-off of 31Jan2023, 15 patients completed 24 weeks of treatment and 11 discontinued due to lack of response (n=5); adverse events (AEs, n=3); and n=1 each lack of response/AE, noncompliance, and erroneous enrollment. At baseline, patients had a median age of 57 y (range, 20-75) with median platelet count of 13x109/L (range, 2-24x109/L). Patients had a median duration of ITP of 10.3 y (range, 0.7-48.2) and had received a median of 6 prior unique ITP therapies (range, 3-19; 46% splenectomy). Prior ITP medication included CS (100%), TPO-RA (85%), immunosuppressants or IVIg (81%), and rituximab (50%). During the study, 17 patients (65%) received concomitant non-rescue CS and/or TPO-RA. The median compliance to rilzabrutinib for patients with 24 weeks of treatment was 99%. Nine patients (35%; 95% CI, 17-56%) achieved the primary endpoint of durable platelet response. Treatment-related AEs were mainly grade 1/2, with no treatment-related grade ≥2 bleeding/thrombotic events or infections, serious AEs, or deaths.

At baseline, the IBLS average score across sites was a mean of 0.27 (SD, 0.27) and mean change from baseline at week 25 was –0.07 (SD, 0.12). The anatomical site with the highest proportion of patients having a baseline score of 2 was skin (n=7 per medical history, n=6 per physical examination), all of whom had a decrease at 25 weeks.

At baseline, median EQ-VAS was 78 (range, 8-100) with a median change from baseline (N=26) to week 25 (n=15) of +7 (range, –5 to 77) indicating an improvement in HRQoL. Median changes in ITP-PAQ domain scores from baseline to week 25 (Figure 1) showed clinically meaningful improvement in women’s reproductive health with a 21-point increase (range, 0-38; median baseline: 54); clinically meaningful improvement in fatigue/sleep, activity, and overall HRQoL scales with ~13-point increases (range, –23 to 75; median baseline: 53, 50, and 52, respectively); and improvement in psychological, symptoms, social activity, and bother-physical health domains with 4- to 8-point increases (range, –13 to 56; median baseline: 70, 60, 75, 69, respectively). Fear and work domains had high scores at baseline (≥90) with minimal changes over time.

Conclusion: Overall, rilzabrutinib showed durable platelet responses, high compliance, and improvements on HRQoL measures in difficult to treat patients with relapsed ITP. There was no evidence of increased bleeding with rilzabrutinib. Clinically meaningful improvements in HRQoL were observed in multiple individual and overall HRQoL health domains following rilzabrutinib.

Disclosures: Tarantino: Spark: Other: Clinical trial investigator; Biomarin: Consultancy; Genentech: Consultancy; Novartis: Consultancy; Takeda: Other: Clinical trial investigator, Research Funding; Amgen: Consultancy; Octapharma: Consultancy, Other: Clinical trial investigator; Principia: Consultancy. Jansen: Erasmus MC: Current Employment; Principia, Argenx, Sobi, Sanofi, CSL Behring: Research Funding; European Patent Office: Patents & Royalties: P133951EP00; Novartis, 3SBIO, Amgen, Sobi: Speakers Bureau; Novartis, Sanofi: Membership on an entity's Board of Directors or advisory committees; 3SBIO, Novartis, Amgen: Other: Travel, accommodations, expenses. Cooper: Rigel: Research Funding; UCB: Honoraria; Sobi: Honoraria; Sanofi: Honoraria; Argenyx: Honoraria; Amgen: Honoraria; Grifols: Honoraria; Novartis: Honoraria, Research Funding. Gouia: Sanofi: Current Employment, Current holder of stock options in a privately-held company. Yao: Sanofi: Current Employment. Daak: Sanofi: Current Employment, Current equity holder in publicly-traded company. Kuter: Rubius: Current equity holder in publicly-traded company; AIRx, Alexion (Syntimmune), Alnylam, Alpine, Amgen, argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, Cellularity, Cellphire, Chugai, CRICO, Daiichi Sankyo, Dianthus, Electra Therapeutics, Fuji, Hemopure, Hengrui. Immunovant, Incyte, Inmagenebio: Consultancy; AIRx, Alexion (Syntimmune), Alnylam, Alpine, Amgen, Argenx, BioCryst, Bristol Myers Squibb (BMS), Caremark, Cellularity, Cellphire, Chugai, CRICO, Daiichi Sankyo, Dianthus, Electra Therapeutics, Fuji, Hemopure, Hengrui, Immunovant, Incyte, Inmagenebio, Ke: Honoraria; UpToDate: Patents & Royalties: UpToDate Chapters; Platelet Disorder Support Association: Membership on an entity's Board of Directors or advisory committees; Kezar, Kyowa-Kirin, Merck Sharp & Dohme: Honoraria; Kezar, Kyowa-Kirin, Merck Sharp Dohme, Momenta, Novartis, Nuvig, Pfizer, Platelet Biogenesis, Platelet Disorder Support Association, Protagonist, Rigel, Sanofi (Bioveratif), Sanofi (Principia), Sanofi (Genzyme), Sobi (Dova), Takeda, UCB, Up-To-Date, Zafge: Consultancy; Alnylam, BioCryst, Novartis, Rigel, Sanofi (Principia), Takeda (Bioverativ), and UCB: Research Funding.

OffLabel Disclosure: Yes, it is off label. Rilzabrutinib is an investigational therapy being evaluated in a clinical study for the treatment of patients with immune thrombocytopenia.

*signifies non-member of ASH