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PHASE I/II STUDY OF RILZABRUTINIB, AN ORAL BRUTON TYROSINE KINASE INHIBITOR, IN PATIENTS WITH IMMUNE THROMBOCYTOPENIA: LONG-TERM FOLLOW-UP
Author(s): ,
David J. Kuter
Affiliations:
Hematology Division,Massachusetts General Hospital, Harvard Medical School,Boston,États-unis;Hematology Division,Massachusetts General Hospital, Harvard Medical School,Boston,Vereinigte Staaten;Hematology Division,Massachusetts General Hospital, Harvard Medical School,Boston,Stati Uniti;Hematology Division,Massachusetts General Hospital, Harvard Medical School,Boston,United States;Hematology Divis
,
Merlin Efraim
Affiliations:
Multiprofile Hospital for Active Treatment Sveta Marina EAD,Varna,Bulgarie;Multiprofile Hospital for Active Treatment Sveta Marina EAD,Varna,Bulgarien;Multiprofile Hospital for Active Treatment Sveta Marina EAD,Varna,Bulgaria;Multiprofile Hospital for Active Treatment Sveta Marina EAD,Varna,Bulgaria;Multiprofile Hospital for Active Treatment Sveta Marina EAD,Varna,Bulgaria;Multiprofile Hospital fo
,
Zane Kaplan
Affiliations:
Monash Medical Centre,Clayton,Australie;Monash Medical Centre,Clayton,Australien;Monash Medical Centre,Clayton,Australia;Monash Medical Centre,Clayton,Australia;Monash Medical Centre,Clayton,Australia;Monash Medical Centre,Clayton,Australië;Monash Medical Centre,Clayton,Austrália;Monash Medical Centre,Clayton,Австралия;Monash Medical Centre,Clayton,Australien
,
Jiri Mayer
Affiliations:
Department of Internal Medicine, Hematology and Oncology, Masaryk University Hospital,Brno,Tchèque, République;Department of Internal Medicine, Hematology and Oncology, Masaryk University Hospital,Brno,Tschechische Republik;Department of Internal Medicine, Hematology and Oncology, Masaryk University Hospital,Brno,Rep. Ceca;Department of Internal Medicine, Hematology and Oncology, Masaryk Universit
,
Philip Choi
Affiliations:
The Canberra Hospital,Garran,Australie;The Canberra Hospital,Garran,Australien;The Canberra Hospital,Garran,Australia;The Canberra Hospital,Garran,Australia;The Canberra Hospital,Garran,Australia;The Canberra Hospital,Garran,Australië;The Canberra Hospital,Garran,Austrália;The Canberra Hospital,Garran,Австралия;The Canberra Hospital,Garran,Australien
,
A.J. Gerard Jansen
Affiliations:
Erasmus MC, University Medical Center,Rotterdam,Pays-bas;Erasmus MC, University Medical Center,Rotterdam,Niederlande;Erasmus MC, University Medical Center,Rotterdam,Paesi Bassi;Erasmus MC, University Medical Center,Rotterdam,Netherland;Erasmus MC, University Medical Center,Rotterdam,Países Bajos;Erasmus MC, University Medical Center,Rotterdam,Nederland;Erasmus MC, University Medical Center,Rotterd
,
Vickie McDonald
Affiliations:
Barts Health NHS Trust, The Royal London Hospital,London,Royaume-uni;Barts Health NHS Trust, The Royal London Hospital,London,Vereinigtes Königreich;Barts Health NHS Trust, The Royal London Hospital,London,Regno Unito;Barts Health NHS Trust, The Royal London Hospital,London,United Kingdom;Barts Health NHS Trust, The Royal London Hospital,London,Reino Unido;Barts Health NHS Trust, The Royal London
,
Ross Baker
Affiliations:
Perth Blood Institute, Murdoch University,Perth,Australie;Perth Blood Institute, Murdoch University,Perth,Australien;Perth Blood Institute, Murdoch University,Perth,Australia;Perth Blood Institute, Murdoch University,Perth,Australia;Perth Blood Institute, Murdoch University,Perth,Australia;Perth Blood Institute, Murdoch University,Perth,Australië;Perth Blood Institute, Murdoch University,Perth,Aus
,
Robert Bird
Affiliations:
Princess Alexandra Hospital ,Woolloongabba,Australie;Princess Alexandra Hospital ,Woolloongabba,Australien;Princess Alexandra Hospital ,Woolloongabba,Australia;Princess Alexandra Hospital ,Woolloongabba,Australia;Princess Alexandra Hospital ,Woolloongabba,Australia;Princess Alexandra Hospital ,Woolloongabba,Australië;Princess Alexandra Hospital ,Woolloongabba,Austrália;Princess Alexandra Hospital
,
Mamta Garg
Affiliations:
Leicester Royal Infirmary,Leicester,Royaume-uni;Leicester Royal Infirmary,Leicester,Vereinigtes Königreich;Leicester Royal Infirmary,Leicester,Regno Unito;Leicester Royal Infirmary,Leicester,United Kingdom;Leicester Royal Infirmary,Leicester,Reino Unido;Leicester Royal Infirmary,Leicester,Verenigd Koninkrijk;Leicester Royal Infirmary,Leicester,Reino Unido;Leicester Royal Infirmary,Leicester,Соедин
,
Jaromir Gumulec
Affiliations:
Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine University of Ostrava,Ostrava,Tchèque, République;Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine University of Ostrava,Ostrava,Tschechische Republik;Department of Hematooncology, University Hospital Ostrava and Faculty of Medicine University of Ostrava,Ostrava,Rep. Ceca;Department o
,
Milan Kostal
Affiliations:
Fourth Department of Internal Medicine and Hematology, Faculty of Medicine, University Hospital of Hradec Kralove,Hradec Kralove,Tchèque, République;Fourth Department of Internal Medicine and Hematology, Faculty of Medicine, University Hospital of Hradec Kralove,Hradec Kralove,Tschechische Republik;Fourth Department of Internal Medicine and Hematology, Faculty of Medicine, University Hospital of H
,
Terry Gernsheimer
Affiliations:
University of Washington Medical Center,Seattle,États-unis;University of Washington Medical Center,Seattle,Vereinigte Staaten;University of Washington Medical Center,Seattle,Stati Uniti;University of Washington Medical Center,Seattle,United States;University of Washington Medical Center,Seattle,Estados Unidos;University of Washington Medical Center,Seattle,Verenigde Staten;University of Washington
,
Waleed Ghanima
Affiliations:
Østfold Hospital Foundation,Gralum,Norvège;Østfold Hospital Foundation,Gralum,Norwegen;Østfold Hospital Foundation,Gralum,Norvegia;Østfold Hospital Foundation,Gralum,Norway;Østfold Hospital Foundation,Gralum,Noruega;Østfold Hospital Foundation,Gralum,Noorwegen;Østfold Hospital Foundation,Gralum,Noruega;Østfold Hospital Foundation,Gralum,Норвегия;Østfold Hospital Foundation,Gralum,Norge
,
Mengjie Yao
Affiliations:
Biostatistics, Sanofi US Services Inc.,Bridgewater,États-unis;Biostatistics, Sanofi US Services Inc.,Bridgewater,Vereinigte Staaten;Biostatistics, Sanofi US Services Inc.,Bridgewater,Stati Uniti;Biostatistics, Sanofi US Services Inc.,Bridgewater,United States;Biostatistics, Sanofi US Services Inc.,Bridgewater,Estados Unidos;Biostatistics, Sanofi US Services Inc.,Bridgewater,Verenigde Staten;Biosta
,
Ahmed Daak
Affiliations:
Sanofi Genzyme,Cambridge,États-unis;Sanofi Genzyme,Cambridge,Vereinigte Staaten;Sanofi Genzyme,Cambridge,Stati Uniti;Sanofi Genzyme,Cambridge,United States;Sanofi Genzyme,Cambridge,Estados Unidos;Sanofi Genzyme,Cambridge,Verenigde Staten;Sanofi Genzyme,Cambridge,Estados Unidos;Sanofi Genzyme,Cambridge,United States;Sanofi Genzyme,Cambridge,USA
Nichola Cooper
Affiliations:
Department of Medicine, Hammersmith Hospital ,London,Royaume-uni;Department of Medicine, Hammersmith Hospital ,London,Vereinigtes Königreich;Department of Medicine, Hammersmith Hospital ,London,Regno Unito;Department of Medicine, Hammersmith Hospital ,London,United Kingdom;Department of Medicine, Hammersmith Hospital ,London,Reino Unido;Department of Medicine, Hammersmith Hospital ,London,Verenigd
(Abstract release date: 05/12/22) EHA Library. Kuter D. 06/11/22; 357155; S291
Dr. David Kuter
Dr. David Kuter
Contributions
Abstract
Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S291

Type: Oral Presentation

Session title: Thrombocytopenia - Management insights in ITP and TTP

Background
Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and high bleeding risk. In a global phase I/II trial (NCT03395210) of heavily pretreated patients with long-standing disease, the Bruton tyrosine kinase inhibitor rilzabrutinib showed a rapid and durable platelet count increase and was well tolerated. We present results for patients initiating rilzabrutinib 400 mg BID who are continuing in the long-term extension (LTE).

Aims
Assess if the efficacy and safety of rilzabrutinib 400 mg BID continue to be maintained in LTE patients on rilzabrutinib ± concomitant medication.

Methods
Patients with 2 baseline platelet counts <30×109/L were required to have responded to ≥1 prior ITP therapy but at baseline were unable to maintain an adequate response to prior/concomitant therapies. The main treatment period was 24 weeks; patients who achieved platelet counts ≥50×109/L at ≥50% of the visits during the last 8 weeks of the main period were permitted to continue 400 mg BID in the LTE. Primary endpoints were safety and efficacy (≥2 consecutive platelet counts ≥50×109/L and increased ≥20×109/L from baseline without requiring rescue medication). Stable doses of concomitant ITP medication (thrombopoietin-receptor agonists [TPO-RA] and corticosteroids [CS]) were allowed for patients with inadequate platelet response. Patients who received rescue medication discontinued from the study. All patients provided informed consent.

Results
At baseline, the 45 patients initiating 400 mg BID in the main period had a median age of 49 years, median duration of ITP of 6.1 years, median platelet count of 15×109/L, and a median of 4 unique prior therapies (24% prior splenectomy). A total of 15 patients (33%) received rilzabrutinib monotherapy, and 30 had concomitant therapy (TPO-RA n=13 [29%], CS n=12 [27%], TPO-RA + CS n=5 [11%]). Primary platelet response was achieved by 18 patients (40%): 6  on monotherapy and 12 on concomitant medication. Platelet counts of ≥50×109/L, ≥30×109/L, and ≥20×109/L from baseline were maintained for a median of 71%, 95%, and 87% of weeks, respectively. As of 21Jan2022, 16/60 patients in the main study population had proceeded to LTE, of whom 11 were ongoing. Five LTE patients (31%) continued on rilzabrutinib monotherapy and 11 used concomitant medication (TPO-RA n=2 [13%], CS n=7 [44%], TPO-RA + CS n=2 [13%]; Figure); 1 patient used rescue medication. Median platelet count at LTE entry was 87×109/L. In patients on rilzabrutinib monotherapy, the median platelet count was 68×109/L, which was sustained at 6 months of follow-up (Table). In all LTE patients, platelet counts ≥50×109/L, ≥30×109/L, and ≥20×109/L from baseline were maintained for a median of 88%, 100%, and 97% of weeks, respectively. In patients on rilzabrutinib ± concomitant medication, results were consistent at 3 and 6 months of follow-up (Table). Three patients (19%) experienced related treatment-emergent adverse events (TEAEs), including 1 grade 2 upper respiratory tract infection. Three patients (19%) discontinued rilzabrutinib due to a TEAE. Six patients had ≥1 bleeding event, none were treatment-related; no related serious adverse events or deaths. The average ITP-BAT bleeding scale score at 6 months showed no increase in bleeding in the LTE.

Conclusion
With extended treatment duration, rilzabrutinib 400 mg BID showed durable clinical efficacy and was well tolerated in patients on rilzabrutinib ± concomitant medication.

Keyword(s): Immune thrombocytopenia (ITP), Inhibitor, Platelet, Platelet count

Presentation during EHA2022: All Oral presentations will be presented between Friday, June 10 and Sunday, June 12 and will be accessible for on-demand viewing from Monday, June 20 until Monday, August 15, 2022 on the Congress platform.

Abstract: S291

Type: Oral Presentation

Session title: Thrombocytopenia - Management insights in ITP and TTP

Background
Immune thrombocytopenia (ITP) is an autoimmune disease associated with autoantibody-mediated platelet destruction and impaired platelet production, resulting in thrombocytopenia and high bleeding risk. In a global phase I/II trial (NCT03395210) of heavily pretreated patients with long-standing disease, the Bruton tyrosine kinase inhibitor rilzabrutinib showed a rapid and durable platelet count increase and was well tolerated. We present results for patients initiating rilzabrutinib 400 mg BID who are continuing in the long-term extension (LTE).

Aims
Assess if the efficacy and safety of rilzabrutinib 400 mg BID continue to be maintained in LTE patients on rilzabrutinib ± concomitant medication.

Methods
Patients with 2 baseline platelet counts <30×109/L were required to have responded to ≥1 prior ITP therapy but at baseline were unable to maintain an adequate response to prior/concomitant therapies. The main treatment period was 24 weeks; patients who achieved platelet counts ≥50×109/L at ≥50% of the visits during the last 8 weeks of the main period were permitted to continue 400 mg BID in the LTE. Primary endpoints were safety and efficacy (≥2 consecutive platelet counts ≥50×109/L and increased ≥20×109/L from baseline without requiring rescue medication). Stable doses of concomitant ITP medication (thrombopoietin-receptor agonists [TPO-RA] and corticosteroids [CS]) were allowed for patients with inadequate platelet response. Patients who received rescue medication discontinued from the study. All patients provided informed consent.

Results
At baseline, the 45 patients initiating 400 mg BID in the main period had a median age of 49 years, median duration of ITP of 6.1 years, median platelet count of 15×109/L, and a median of 4 unique prior therapies (24% prior splenectomy). A total of 15 patients (33%) received rilzabrutinib monotherapy, and 30 had concomitant therapy (TPO-RA n=13 [29%], CS n=12 [27%], TPO-RA + CS n=5 [11%]). Primary platelet response was achieved by 18 patients (40%): 6  on monotherapy and 12 on concomitant medication. Platelet counts of ≥50×109/L, ≥30×109/L, and ≥20×109/L from baseline were maintained for a median of 71%, 95%, and 87% of weeks, respectively. As of 21Jan2022, 16/60 patients in the main study population had proceeded to LTE, of whom 11 were ongoing. Five LTE patients (31%) continued on rilzabrutinib monotherapy and 11 used concomitant medication (TPO-RA n=2 [13%], CS n=7 [44%], TPO-RA + CS n=2 [13%]; Figure); 1 patient used rescue medication. Median platelet count at LTE entry was 87×109/L. In patients on rilzabrutinib monotherapy, the median platelet count was 68×109/L, which was sustained at 6 months of follow-up (Table). In all LTE patients, platelet counts ≥50×109/L, ≥30×109/L, and ≥20×109/L from baseline were maintained for a median of 88%, 100%, and 97% of weeks, respectively. In patients on rilzabrutinib ± concomitant medication, results were consistent at 3 and 6 months of follow-up (Table). Three patients (19%) experienced related treatment-emergent adverse events (TEAEs), including 1 grade 2 upper respiratory tract infection. Three patients (19%) discontinued rilzabrutinib due to a TEAE. Six patients had ≥1 bleeding event, none were treatment-related; no related serious adverse events or deaths. The average ITP-BAT bleeding scale score at 6 months showed no increase in bleeding in the LTE.

Conclusion
With extended treatment duration, rilzabrutinib 400 mg BID showed durable clinical efficacy and was well tolerated in patients on rilzabrutinib ± concomitant medication.

Keyword(s): Immune thrombocytopenia (ITP), Inhibitor, Platelet, Platelet count

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