EHA Library - The official digital education library of European Hematology Association (EHA)

ZANUBRUTINIB + OBINUTUZUMAB (ZO) VS OBINUTUZUMAB (O) MONOTHERAPY IN PATIENTS (PTS) WITH RELAPSED OR REFRACTORY (R/R) FOLLICULAR LYMPHOMA (FL): PRIMARY ANALYSIS OF THE PHASE 2 RANDOMIZED ROSEWOOD TRIAL
Author(s): ,
Pier Luigi Zinzani
Affiliations:
Institute of Hematology 'Seràgnoli', University of Bologna,Bologna,Italie;Institute of Hematology 'Seràgnoli', University of Bologna,Bologna,Italien;Institute of Hematology 'Seràgnoli', University of Bologna,Bologna,Italia;Institute of Hematology 'Seràgnoli', University of Bologna,Bologna,Italy;Institute of Hematology 'Seràgnoli', University of Bologna,Bologna,Italia;Institute of Hematology 'Seràg
,
Jiří Mayer
Affiliations:
Department of Internal Medicine-Hematology and Oncology,Masaryk University and University Hospital,Brno,Tchèque, République;Department of Internal Medicine-Hematology and Oncology,Masaryk University and University Hospital,Brno,Tschechische Republik;Department of Internal Medicine-Hematology and Oncology,Masaryk University and University Hospital,Brno,Rep. Ceca;Department of Internal Medicine-Hema
,
Rebecca Auer
Affiliations:
St. Bartholomew's Hospital, Barts Health NHS Trust,London,Royaume-uni;St. Bartholomew's Hospital, Barts Health NHS Trust,London,Vereinigtes Königreich;St. Bartholomew's Hospital, Barts Health NHS Trust,London,Regno Unito;St. Bartholomew's Hospital, Barts Health NHS Trust,London,United Kingdom;St. Bartholomew's Hospital, Barts Health NHS Trust,London,Reino Unido;St. Bartholomew's Hospital, Barts He
,
Fontanet Bijou
Affiliations:
Institut Bergonié,Bordeaux,France;Institut Bergonié,Bordeaux,Frankreich;Institut Bergonié,Bordeaux,Francia;Institut Bergonié,Bordeaux,France;Institut Bergonié,Bordeaux,Francia;Institut Bergonié,Bordeaux,Frankrijk;Institut Bergonié,Bordeaux,França;Institut Bergonié,Bordeaux,Франция ;Institut Bergonié,Bordeaux,Frankrike
,
Ana C. de Oliveira
Affiliations:
Institut Catala d'Oncologia (ICO) Hospital Duran I Reynals, Hospital,Barcelona,Espagne;Institut Catala d'Oncologia (ICO) Hospital Duran I Reynals, Hospital,Barcelona,Spanien;Institut Catala d'Oncologia (ICO) Hospital Duran I Reynals, Hospital,Barcelona,Spagna;Institut Catala d'Oncologia (ICO) Hospital Duran I Reynals, Hospital,Barcelona,Spain;Institut Catala d'Oncologia (ICO) Hospital Duran I Reyn
,
Christopher R. Flowers
Affiliations:
Department of Lymphoma/Myeloma,The University of Texas MD Anderson Cancer Center,Houston, TX,États-unis;Department of Lymphoma/Myeloma,The University of Texas MD Anderson Cancer Center,Houston, TX,Vereinigte Staaten;Department of Lymphoma/Myeloma,The University of Texas MD Anderson Cancer Center,Houston, TX,Stati Uniti;Department of Lymphoma/Myeloma,The University of Texas MD Anderson Cancer Cente
,
Michele Merli
Affiliations:
Hematology,University Hospital "Ospedale di Circolo e Fondazione Macchi" - ASST Sette Laghi, University of Insubria,Varese,Italie;Hematology,University Hospital "Ospedale di Circolo e Fondazione Macchi" - ASST Sette Laghi, University of Insubria,Varese,Italien;Hematology,University Hospital "Ospedale di Circolo e Fondazione Macchi" - ASST Sette Laghi, University of Insubria,Varese,Italia;Hematolog
,
Krimo Bouabdallah
Affiliations:
Hôpital Haut-Lévêque, CHU Bordeaux,Pessac,France;Hôpital Haut-Lévêque, CHU Bordeaux,Pessac,Frankreich;Hôpital Haut-Lévêque, CHU Bordeaux,Pessac,Francia;Hôpital Haut-Lévêque, CHU Bordeaux,Pessac,France;Hôpital Haut-Lévêque, CHU Bordeaux,Pessac,Francia;Hôpital Haut-Lévêque, CHU Bordeaux,Pessac,Frankrijk;Hôpital Haut-Lévêque, CHU Bordeaux,Pessac,França;Hôpital Haut-Lévêque, CHU Bordeaux,Pessac,Франци
,
Peter S. Ganly
Affiliations:
Department of Haematology,Christchurch Hospital,Christchurch,Nouvelle-zélande;Department of Haematology,Christchurch Hospital,Christchurch,Neuseeland;Department of Haematology,Christchurch Hospital,Christchurch,Nuova Zelanda;Department of Haematology,Christchurch Hospital,Christchurch,新西兰;Department of Haematology,Christchurch Hospital,Christchurch,Nueva Zelanda;Department of Haematology,Christchu
,
Yuqin Song
Affiliations:
Beijing Cancer Hospital,Beijing,Chine;Beijing Cancer Hospital,Beijing,China;Beijing Cancer Hospital,Beijing,Cina;Beijing Cancer Hospital,Beijing,China;Beijing Cancer Hospital,Beijing,China;Beijing Cancer Hospital,Beijing,China;Beijing Cancer Hospital,Beijing,China;Beijing Cancer Hospital,Beijing,China;Beijing Cancer Hospital,Beijing,Kina
,
Huilai Zhang
Affiliations:
Tianjin Medical University Cancer Institute & Hospital,Tianjin,Chine;Tianjin Medical University Cancer Institute & Hospital,Tianjin,China;Tianjin Medical University Cancer Institute & Hospital,Tianjin,Cina;Tianjin Medical University Cancer Institute & Hospital,Tianjin,China;Tianjin Medical University Cancer Institute & Hospital,Tianjin,China;Tianjin Medical
,
Roderick Johnson
Affiliations:
St. James's University Hospital Trust,Leeds,Royaume-uni;St. James's University Hospital Trust,Leeds,Vereinigtes Königreich;St. James's University Hospital Trust,Leeds,Regno Unito;St. James's University Hospital Trust,Leeds,United Kingdom;St. James's University Hospital Trust,Leeds,Reino Unido;St. James's University Hospital Trust,Leeds,Verenigd Koninkrijk;St. James's University Hospital Trust,Leed
,
Alejandro Martín García-Sancho
Affiliations:
Hospital Universitario de Salamanca,Salamanca,Espagne;Hospital Universitario de Salamanca,Salamanca,Spanien;Hospital Universitario de Salamanca,Salamanca,Spagna;Hospital Universitario de Salamanca,Salamanca,Spain;Hospital Universitario de Salamanca,Salamanca,España;Hospital Universitario de Salamanca,Salamanca,Spanje;Hospital Universitario de Salamanca,Salamanca,Espanha;Hospital Universitario de S
,
Mariano Provencio
Affiliations:
Hospital Universitario Puerta de Hierro — Majadahonda,Madrid,Espagne;Hospital Universitario Puerta de Hierro — Majadahonda,Madrid,Spanien;Hospital Universitario Puerta de Hierro — Majadahonda,Madrid,Spagna;Hospital Universitario Puerta de Hierro — Majadahonda,Madrid,Spain;Hospital Universitario Puerta de Hierro — Majadahonda,Madrid,España;Hospital Universitario Puerta de Hierro — Majadahonda,Madri
,
Marek Trněný
Affiliations:
Vseobecna fakultní nemocnice v Praze,Prague,Tchèque, République;Vseobecna fakultní nemocnice v Praze,Prague,Tschechische Republik;Vseobecna fakultní nemocnice v Praze,Prague,Rep. Ceca;Vseobecna fakultní nemocnice v Praze,Prague,Czech;Vseobecna fakultní nemocnice v Praze,Prague,República Checa;Vseobecna fakultní nemocnice v Praze,Prague,Tsjechische Republiek;Vseobecna fakultní nemocnice v Praze,Pra
,
Sam Yuen
Affiliations:
Calvary Mater Newcastle,Waratah, New South Wales,Australie;Calvary Mater Newcastle,Waratah, New South Wales,Australien;Calvary Mater Newcastle,Waratah, New South Wales,Australia;Calvary Mater Newcastle,Waratah, New South Wales,Australia;Calvary Mater Newcastle,Waratah, New South Wales,Australia;Calvary Mater Newcastle,Waratah, New South Wales,Australië;Calvary Mater Newcastle,Waratah, New South Wa
,
Herve Tilly
Affiliations:
Centre Henri-Becquerel,Rouen,France;Centre Henri-Becquerel,Rouen,Frankreich;Centre Henri-Becquerel,Rouen,Francia;Centre Henri-Becquerel,Rouen,France;Centre Henri-Becquerel,Rouen,Francia;Centre Henri-Becquerel,Rouen,Frankrijk;Centre Henri-Becquerel,Rouen,França;Centre Henri-Becquerel,Rouen,Франция ;Centre Henri-Becquerel,Rouen,Frankrike
,
Edwin Kingsley
Affiliations:
Comprehensive Cancer Centers of Nevada,Las Vegas, NV,États-unis;Comprehensive Cancer Centers of Nevada,Las Vegas, NV,Vereinigte Staaten;Comprehensive Cancer Centers of Nevada,Las Vegas, NV,Stati Uniti;Comprehensive Cancer Centers of Nevada,Las Vegas, NV,United States;Comprehensive Cancer Centers of Nevada,Las Vegas, NV,Estados Unidos;Comprehensive Cancer Centers of Nevada,Las Vegas, NV,Verenigde S
,
Gayane Tuyman
Affiliations:
Department of Chemotherapy of Hemoblastosis,Blokhin Russian Cancer Research Center,Moscow,Russie, Fédération De;Department of Chemotherapy of Hemoblastosis,Blokhin Russian Cancer Research Center,Moscow,Russia;Department of Chemotherapy of Hemoblastosis,Blokhin Russian Cancer Research Center,Moscow,Russia;Department of Chemotherapy of Hemoblastosis,Blokhin Russian Cancer Research Center,Moscow,Russ
,
Sarit E. Assouline
Affiliations:
Jewish General Hospital,Montreal,Canada;Jewish General Hospital,Montreal,Kanada;Jewish General Hospital,Montreal,Canada;Jewish General Hospital,Montreal,Canada;Jewish General Hospital,Montreal,Canadá;Jewish General Hospital,Montreal,Canada;Jewish General Hospital,Montreal,Canadá;Jewish General Hospital,Montreal,Канада;Jewish General Hospital,Montreal,Kanada
,
Elena Ivanova
Affiliations:
BeiGene Switzerland GmbH,Basel,Suisse;BeiGene Switzerland GmbH,Basel,Schweiz;BeiGene Switzerland GmbH,Basel,Svizzera;BeiGene Switzerland GmbH,Basel,Switzerland;BeiGene Switzerland GmbH,Basel,Suiza;BeiGene Switzerland GmbH,Basel,Zwitserland;BeiGene Switzerland GmbH,Basel,Suíça;BeiGene Switzerland GmbH,Basel,Швейцария ;BeiGene Switzerland GmbH,Basel,Schweiz
,
Pil Kim
Affiliations:
BeiGene (Beijing) Co., Ltd., Beijing, China and BeiGene USA, Inc.,San Mateo, CA,États-unis;BeiGene (Beijing) Co., Ltd., Beijing, China and BeiGene USA, Inc.,San Mateo, CA,Vereinigte Staaten;BeiGene (Beijing) Co., Ltd., Beijing, China and BeiGene USA, Inc.,San Mateo, CA,Stati Uniti;BeiGene (Beijing) Co., Ltd., Beijing, China and BeiGene USA, Inc.,San Mateo, CA,United States;BeiGene (Beijing) Co., L
,
Jane Huang
Affiliations:
BeiGene (Beijing) Co., Ltd., Beijing, China and BeiGene USA, Inc.,San Mateo, CA,États-unis;BeiGene (Beijing) Co., Ltd., Beijing, China and BeiGene USA, Inc.,San Mateo, CA,Vereinigte Staaten;BeiGene (Beijing) Co., Ltd., Beijing, China and BeiGene USA, Inc.,San Mateo, CA,Stati Uniti;BeiGene (Beijing) Co., Ltd., Beijing, China and BeiGene USA, Inc.,San Mateo, CA,United States;BeiGene (Beijing) Co., L
,
Richard Delarue
Affiliations:
BeiGene Switzerland GmbH,Basel,Suisse;BeiGene Switzerland GmbH,Basel,Schweiz;BeiGene Switzerland GmbH,Basel,Svizzera;BeiGene Switzerland GmbH,Basel,Switzerland;BeiGene Switzerland GmbH,Basel,Suiza;BeiGene Switzerland GmbH,Basel,Zwitserland;BeiGene Switzerland GmbH,Basel,Suíça;BeiGene Switzerland GmbH,Basel,Швейцария ;BeiGene Switzerland GmbH,Basel,Schweiz
Judith Trotman
Affiliations:
Concord Repatriation General Hospital,Concord, New South Wales,Australie;Concord Repatriation General Hospital,Concord, New South Wales,Australien;Concord Repatriation General Hospital,Concord, New South Wales,Australia;Concord Repatriation General Hospital,Concord, New South Wales,Australia;Concord Repatriation General Hospital,Concord, New South Wales,Australia;Concord Repatriation General Hospi
(Abstract release date: 05/26/22) EHA Library. Luigi Zinzani P. 06/11/22; 357069; S205
Prof. Dr. Pier Luigi Zinzani
Prof. Dr. Pier Luigi Zinzani
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: S205

Type: Oral Presentation

Session title: Indolent and mantle cell lymphoma

Background
FL is the most common type of indolent non-Hodgkin lymphoma. Approved treatment options are limited for pts with R/R FL. In a phase 1b trial (Blood Adv. 2020;4(19):4802-4811), ZO was found to be tolerable and associated with early signal of efficacy.

Aims
To present a primary analysis of ROSEWOOD (BGB-3111-212; NCT03332017), a phase 2, randomized study designed to assess efficacy and safety of ZO vs O in pts with R/R FL.

Methods
Pts with R/R FL who received ≥2 lines of therapy, including an anti-CD20 antibody and an alkylating agent, were randomized 2:1 to receive either ZO or O. O was given in both arms on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6, and then every 8 weeks up to 20 doses maximum. Z (160 mg twice daily) was given until progressive disease (PD) or unacceptable toxicity; pts with confirmed PD or no response within 12 months in the O arm were allowed to crossover to ZO. Primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints included complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoint included ORR by investigator after crossover. Primary analysis cutoff was October 8, 2021. All pts gave informed consent.

Results
A total of 217 pts were randomized to ZO (n=145) or O (n=72). Median study follow-up was 12.5 mo; median age was 64 yrs. Incidence of high FL International Prognostic Index score was 53% (ZO) and 51% (O). Pts received a median of 3 prior lines of therapy, with 28% (ZO) and 25% (O) of pts receiving >3 lines. Proportion of pts refractory to rituximab, refractory to the most recent line of therapy, or with PD within 24 mo of initiation of first-line therapy was 54%, 32%, and 35% with ZO and 50%, 40%, and 42% with O, respectively. The study met its primary endpoint: ORR was 68.3% with ZO vs 45.8% with O (p=0.0017). CRR was 37.2% (ZO) vs 19.4% (O); 18-mo DOR rate was 70.9% (ZO) vs 54.6% (O); and median PFS was 27.4 mo (ZO) vs 11.2 mo (O; hazard ratio [HR], 0.51 [95% CI, 0.32-0.81], p=0.0040). Median time to new anti-lymphoma therapy or crossover was not evaluable (ZO; NE) vs 12.1 mo (O; HR, 0.37 [95% CI, 0.23-0.60], p<0.0001). ORR for 29 pts who crossed over to ZO was 24.1%. Median OS was NE; 18-mo OS probability was 85.4% (ZO) vs 72.6% (O). Most common any-grade adverse events (AEs) with incidence >10% in the ZO arm were thrombocytopenia (34.3%), neutropenia (27.3%), diarrhea (16.1%), fatigue (14.0%), constipation (13.3%), cough (11.9%), pyrexia (11.2%), and dyspnea (10.5%). Grade ≥3 AEs with incidence >5% with ZO were neutropenia (22.4%) and thrombocytopenia (14.0%); incidence of atrial fibrillation was 0.7% and major hemorrhage was 1.4%. Incidence of treatment-emergent AEs leading to death was 5.6% (ZO) and 9.9% (O).

Conclusion
ZO demonstrated superior efficacy to O in treatment of pts with R/R FL. ZO had a favorable benefit-risk profile and represents a potential combination therapy for pts with R/R FL.

Keyword(s): Follicular lymphoma, Kinase, Non-Hodgkin's lymphoma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.
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: S205

Type: Oral Presentation

Session title: Indolent and mantle cell lymphoma

Background
FL is the most common type of indolent non-Hodgkin lymphoma. Approved treatment options are limited for pts with R/R FL. In a phase 1b trial (Blood Adv. 2020;4(19):4802-4811), ZO was found to be tolerable and associated with early signal of efficacy.

Aims
To present a primary analysis of ROSEWOOD (BGB-3111-212; NCT03332017), a phase 2, randomized study designed to assess efficacy and safety of ZO vs O in pts with R/R FL.

Methods
Pts with R/R FL who received ≥2 lines of therapy, including an anti-CD20 antibody and an alkylating agent, were randomized 2:1 to receive either ZO or O. O was given in both arms on Days 1, 8, and 15 of Cycle 1, Day 1 of Cycles 2-6, and then every 8 weeks up to 20 doses maximum. Z (160 mg twice daily) was given until progressive disease (PD) or unacceptable toxicity; pts with confirmed PD or no response within 12 months in the O arm were allowed to crossover to ZO. Primary endpoint was overall response rate (ORR) by independent central review. Secondary endpoints included complete response rate (CRR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Exploratory endpoint included ORR by investigator after crossover. Primary analysis cutoff was October 8, 2021. All pts gave informed consent.

Results
A total of 217 pts were randomized to ZO (n=145) or O (n=72). Median study follow-up was 12.5 mo; median age was 64 yrs. Incidence of high FL International Prognostic Index score was 53% (ZO) and 51% (O). Pts received a median of 3 prior lines of therapy, with 28% (ZO) and 25% (O) of pts receiving >3 lines. Proportion of pts refractory to rituximab, refractory to the most recent line of therapy, or with PD within 24 mo of initiation of first-line therapy was 54%, 32%, and 35% with ZO and 50%, 40%, and 42% with O, respectively. The study met its primary endpoint: ORR was 68.3% with ZO vs 45.8% with O (p=0.0017). CRR was 37.2% (ZO) vs 19.4% (O); 18-mo DOR rate was 70.9% (ZO) vs 54.6% (O); and median PFS was 27.4 mo (ZO) vs 11.2 mo (O; hazard ratio [HR], 0.51 [95% CI, 0.32-0.81], p=0.0040). Median time to new anti-lymphoma therapy or crossover was not evaluable (ZO; NE) vs 12.1 mo (O; HR, 0.37 [95% CI, 0.23-0.60], p<0.0001). ORR for 29 pts who crossed over to ZO was 24.1%. Median OS was NE; 18-mo OS probability was 85.4% (ZO) vs 72.6% (O). Most common any-grade adverse events (AEs) with incidence >10% in the ZO arm were thrombocytopenia (34.3%), neutropenia (27.3%), diarrhea (16.1%), fatigue (14.0%), constipation (13.3%), cough (11.9%), pyrexia (11.2%), and dyspnea (10.5%). Grade ≥3 AEs with incidence >5% with ZO were neutropenia (22.4%) and thrombocytopenia (14.0%); incidence of atrial fibrillation was 0.7% and major hemorrhage was 1.4%. Incidence of treatment-emergent AEs leading to death was 5.6% (ZO) and 9.9% (O).

Conclusion
ZO demonstrated superior efficacy to O in treatment of pts with R/R FL. ZO had a favorable benefit-risk profile and represents a potential combination therapy for pts with R/R FL.

Keyword(s): Follicular lymphoma, Kinase, Non-Hodgkin's lymphoma



© 2022 American Society of Clinical Oncology, Inc. Reused with permission. This abstract was accepted and previously presented at the 2022 ASCO Annual Meeting. All rights reserved.

By clicking “Accept Terms & all Cookies” or by continuing to browse, you agree to the storing of third-party cookies on your device to enhance your user experience and agree to the user terms and conditions of this learning management system (LMS).

Cookie Settings
Accept Terms & all Cookies