PHASE 1/2 STUDY OF SINGLE-AGENT ZANUBRUTINIB IN PATIENTS WITH RELAPSED/REFRACTORY MARGINAL ZONE LYMPHOMA
Author(s): ,
Alessandra Tedeschi
Affiliations:
ASST Grande Osperdale Metropolitano Niguarda,Milan,Italy
,
Judith Trotman
Affiliations:
Concord Repatriation General Hospital,Concord, New South Wales,Australia;University of Sydney,Concord, New South Wales,Australia
,
Constantine Tam
Affiliations:
Peter MacCallum Cancer Centre,Melbourne, Victoria,Australia;St Vincent's Hospita,Fitzroy, Victoria,Australia;University of Melbourne,Parkville, Victoria,Australia;Royal Melbourne Hospital,Parkville, Victoria,Australia
,
David Simpson
Affiliations:
North Shore Hospital,Auckland,New Zealand;BeiGene USA, Inc.,San Mateo, CA,United States
,
Hyeon-Seok Eom
Affiliations:
National Cancer Center – Korea,Goyang-si Gyeonggi-do,Korea, Republic Of
,
Rebecca Elstrom
Affiliations:
BeiGene USA, Inc.,San Mateo, CA,United States
,
Ziwen Tan
Affiliations:
BeiGene (Beijing) Co., Ltd.,Beijing,China
,
Jennifer C. Stern
Affiliations:
BeiGene USA, Inc.,San Mateo, CA,United States
,
Siminder K. Atwal
Affiliations:
BeiGene USA, Inc.,San Mateo, CA,United States
,
William Novotny
Affiliations:
BeiGene USA, Inc.,San Mateo, CA,United States
,
Jane Huang
Affiliations:
BeiGene USA, Inc.,San Mateo, CA,United States
Stephen Opat
Affiliations:
Monash Health,Clayton, Victoria,Australia;Monash University,Clayton, Victoria,Australia
EHA Library. Tedeschi A. 06/12/20; 293654; EP1165
Dr. A Tedeschi
Dr. A Tedeschi
Contributions
Abstract

Abstract: EP1165

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
Marginal zone lymphoma (MZL) is the third most common lymphoma and represents approximately 5% to 15% of all non-Hodgkin lymphomas. Improved understanding of the disease biology, including genetic and molecular characteristics, has changed the therapeutic landscape of MZL, and there is increasing evidence that targeted therapies, including Bruton tyrosine kinase inhibitors, have improved efficacy and have shown tolerable toxicity profiles over chemotherapy-based approaches. Zanubrutinib, a potent and selective Bruton tyrosine kinase inhibitor, has established therapeutic activity in B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström macroglobulinemia.

Aims
To examine the safety and preliminary efficacy of single-agent zanubrutinib in a phase 1/2 study of patients with relapsed/refractory MZL.

Methods
Treatment consisted of oral zanubrutinib at 160 mg twice daily (n=17) or 320 mg once daily (n=3) until disease progression or unacceptable toxicity. Efficacy end points included the proportion of patients achieving a complete or partial response in accordance with Lugano classification (J Clin Oncol. 2014;32:3059).

Results
Between September 2014 and August 2018, 20 patients with relapsed/refractory MZL started treatment with zanubrutinib; 65% of patients were aged >65, and 15% were aged >75 years. Patient distribution across MZL subtypes was as follows: extranodal (mucosa-associated lymphoid tissue), 45%; splenic, 30%; and nodal, 25%. The median number of prior therapies was 2, with RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) being the most common type of therapy. At a median follow-up of 22.16 months, 60% of patients remained on treatment. Reasons for treatment discontinuation included disease progression (25%), adverse events (AEs) in 5% of patients (with 1 patient having treatment-related diarrhea), patient’s withdrawal of consent (5%), and other (5%). Therapy was well-tolerated, with the most commonly reported AEs (≥20%) being contusion (35%), diarrhea (35%), upper respiratory tract infection (30%), rash (30%), pyrexia (25%), sinusitis (20%), nausea (20%), and nasopharyngitis (20%). AEs of interest included neutropenia (30%), major hemorrhage (1 patient), and grade 3 diarrhea (1 patient). No patients experienced atrial fibrillation/flutter. Investigator-assessed overall response rate was 75%, and complete response rate was 10% (Table). Median time to response was 2.9 months. Median duration of response (complete or partial response) was not reached (95% CI, 6.47 months to not evaluable) at a median response follow-up of 12 months. Rates of progression-free survival at 12 and 18 months were 77% and 69.3%, respectively. Rate of overall survival at both 12 and 18 months was 100%.

Conclusion
Zanubrutinib treatment demonstrated deep and durable responses in patients with MZL. Treatment discontinuation from AEs was uncommon, with no grade 5 AEs. The safety profile of zanubrutinib therapy in these patients was favorable and consistent with that in prior studies.

Session topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Keyword(s): B cell lymphoma, Kinase inhibitor, Lymphoma, Marginal zone

Abstract: EP1165

Type: e-Poster

Presentation during EHA25: All e-Poster presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Background
Marginal zone lymphoma (MZL) is the third most common lymphoma and represents approximately 5% to 15% of all non-Hodgkin lymphomas. Improved understanding of the disease biology, including genetic and molecular characteristics, has changed the therapeutic landscape of MZL, and there is increasing evidence that targeted therapies, including Bruton tyrosine kinase inhibitors, have improved efficacy and have shown tolerable toxicity profiles over chemotherapy-based approaches. Zanubrutinib, a potent and selective Bruton tyrosine kinase inhibitor, has established therapeutic activity in B-cell malignancies including chronic lymphocytic leukemia, mantle cell lymphoma, and Waldenström macroglobulinemia.

Aims
To examine the safety and preliminary efficacy of single-agent zanubrutinib in a phase 1/2 study of patients with relapsed/refractory MZL.

Methods
Treatment consisted of oral zanubrutinib at 160 mg twice daily (n=17) or 320 mg once daily (n=3) until disease progression or unacceptable toxicity. Efficacy end points included the proportion of patients achieving a complete or partial response in accordance with Lugano classification (J Clin Oncol. 2014;32:3059).

Results
Between September 2014 and August 2018, 20 patients with relapsed/refractory MZL started treatment with zanubrutinib; 65% of patients were aged >65, and 15% were aged >75 years. Patient distribution across MZL subtypes was as follows: extranodal (mucosa-associated lymphoid tissue), 45%; splenic, 30%; and nodal, 25%. The median number of prior therapies was 2, with RCVP (rituximab, cyclophosphamide, vincristine, and prednisone) being the most common type of therapy. At a median follow-up of 22.16 months, 60% of patients remained on treatment. Reasons for treatment discontinuation included disease progression (25%), adverse events (AEs) in 5% of patients (with 1 patient having treatment-related diarrhea), patient’s withdrawal of consent (5%), and other (5%). Therapy was well-tolerated, with the most commonly reported AEs (≥20%) being contusion (35%), diarrhea (35%), upper respiratory tract infection (30%), rash (30%), pyrexia (25%), sinusitis (20%), nausea (20%), and nasopharyngitis (20%). AEs of interest included neutropenia (30%), major hemorrhage (1 patient), and grade 3 diarrhea (1 patient). No patients experienced atrial fibrillation/flutter. Investigator-assessed overall response rate was 75%, and complete response rate was 10% (Table). Median time to response was 2.9 months. Median duration of response (complete or partial response) was not reached (95% CI, 6.47 months to not evaluable) at a median response follow-up of 12 months. Rates of progression-free survival at 12 and 18 months were 77% and 69.3%, respectively. Rate of overall survival at both 12 and 18 months was 100%.

Conclusion
Zanubrutinib treatment demonstrated deep and durable responses in patients with MZL. Treatment discontinuation from AEs was uncommon, with no grade 5 AEs. The safety profile of zanubrutinib therapy in these patients was favorable and consistent with that in prior studies.

Session topic: 18. Indolent and mantle-cell non-Hodgkin lymphoma - Clinical

Keyword(s): B cell lymphoma, Kinase inhibitor, Lymphoma, Marginal zone

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