OC 65.1 - Long-Term Efficacy and Safety With Oral Bruton Tyrosine Kinase Inhibitor Rilzabrutinib in Patients With Immune Thrombocytopenia

Tuesday, June 27, 2023

14:45 – 15:00 ET

Room: 510

Session Available As: On-Demand

Presenting Author(s)

David J. J. Kuter, MD, DPhil

Director of Clinical Hematology
Hematology Division, Massachusetts General Hospital, Harvard Medical School
Boston, Massachusetts, United States

Co-Author(s)

ME

Merlin Efraim

Hematology
Multiprofile Hospital for Active Treatment Sveta Marina EAD
Varna, Varna, Bulgaria
ZK

Zane Kaplan

Consultant Haematologist
Monash Medical Centre
Clayton, Victoria, Australia
JM

Jiri Mayer

Department head, Department of Internal Medicine, Hematology and Oncology
Department of Internal Medicine, Hematology and Oncology, Masaryk University Hospital
Brno, Jihomoravsky kraj, Czech Republic
Philip Choi, MBBS PhD FRACP FRCPA

Haematologist
Canberra Hospital
Canberra, Australian Capital Territory, Australia
GA

Gerard A. J. Jansen

Internist hematologist
Department of Hematology, Erasmus MC, University Medical Center
Rotterdam, Zuid-Holland, Netherlands
VM

Vickie McDonald

Consultant Haematologist
Barts Health NHS Trust, The Royal London Hospital
London, England, United Kingdom
Ross Baker, MD

Professor of Haematology
Health Futures Institute, Murdoch University, Perth, Australia
Perth, Western Australia, Australia
RB

Robert Bird

Director of Haematology
Princess Alexandra Hospital
Woolloongabba, Queensland, Australia
MG

Mamta Garg

Head of Service
Leicester Royal Infirmary
Leicester, England, United Kingdom
JG

Jaromír Gumulec

Deputy Head Physician for Health Care
Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine University of Ostrava
Ostrava, Moravskoslezsky kraj, Czech Republic
MK

Milan Košťál

Fourth Department of Internal Medicine and Hematology, Faculty of Medicine
University Hospital of Hradec Králové
Hradec Králové, Kralovehradecky kraj, Czech Republic
TG

Terry Gernsheimer

Hematology
University of Washington Medical Center
Seattle, Washington, United States
Waleed Ghanima, MD

Professor
Østfold Hospital Foundation
Gralum, Ostfold, Norway
UK

Umer Khan

Biostatistics Lead
Sanofi, San Diego, CA, USA
San Diego, California, United States
AD

Ahmed Daak

Senior Clinical Research Director
Sanofi Genzyme
Bridgewater, New Jersey, United States
Nichola Cooper, MS (Cantab), MBBS, MD, FRCP, FRCPath,

Department of Medicine
Hammersmith Hospital
London, England, United Kingdom

Background: Adult patients with immune thrombocytopenia (ITP) treated with rilzabrutinib showed rapid and durable platelet response and acceptable safety profiles in global phase I/II trial (NCT03395210).

Aims: Report updated efficacy and safety of rilzabrutinib on patients receiving 400 mg BID for 2 y in long-term extension (LTE)

Methods: ITP patients with 2 baseline platelet counts < 30×10^9/L who responded to ≥1 prior ITP therapy but were unable to maintain adequate response to prior/concomitant therapies enrolled in the main study. Primary endpoints were safety and platelet response (≥2 consecutive platelet counts ≥50×10^9/L and increased ≥20×10^9/L from baseline without rescue medication). Patients in the main 24-week study were eligible for LTE if platelet count ≥50×10^9/L for ≥50% of last 8 weeks of treatment.

Results: As of 21December2022, 16 of 60 patients from the main study enrolled in LTE on rilzabrutinib 400 mg BID (n=11 with concomitant CS and/or TPO-RA). At enrollment, patients had median duration of ITP for 4.3 y, received a median of 3 (range, 1-9) unique prior therapies; 3 were splenectomized. The median treatment duration for main+LTE periods was 1032 days (range, 318-1506). Figure 1 shows median platelet counts over time. All LTE patients met the primary endpoint with median platelet count at LTE entry of 87×10^9/L. After LTE entry, median platelet counts for LTE patients were 92×10^9/L, 71×10^9/L, 61×10^9/L, and 64×10^9/L at 3, 6, 12, and 24 months, respectively. Table 1 shows platelet counts above various LTE thresholds; 14 (88%) patients achieved platelet counts ≥100×10^9/L during the LTE. Two patients received rescue medication during the LTE. All treatment-related adverse events were transient, grade 1/2 events with no related bleeding or thrombotic events, serious adverse events, or deaths.

Conclusion(s): With continued treatment through the LTE, rilzabrutinib 400 mg BID demonstrated durable clinical activity and remains well tolerated in patients with ITP.

Learning Objectives:

To review the use of Bruton kinase inhibition in ITP
To assess longterm treatment efficacy of BTK inhibition in ITP
To assess longterm treatment adverse effects of BTK inhibition in ITP