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Background: BCR signaling mediated through Bruton's tyrosine kinase (BTK) plays a critical role in the development and maintenance of marginal zone lymphoma (MZL). BTK inhibitors have established activity in relapsed/refractory (R/R) MZL with the phase 2 study of ibrutinib demonstrating an objective response rate (ORR) of 48% (Noy et al. Blood. 2017;129:2224-2232). Zanubrutinib is a potent and highly specific next-generation BTK inhibitor designed with greater selectivity for BTK vs TEC- and EGFRfamily kinases, which are thought to be related to off-target toxicities. Therapeutic activity of zanubrutinib was established in an early-phase study (BGB-3111-AU-003) of 20 patients (pts) with R/R MZL demonstrating an ORR of 80%, with a complete response (CR) rate of 15%, and partial response (PR) rate of 65% (Tedeschi et al. EHA 2020, abstract 2804). Aim(s): To present initial efficacy and safety results in pts with R/R MZL enrolled in MAGNOLIA (BGB-3111-214). Method(s): MAGNOLIA is a phase 2, multicenter, single-arm study of adults with R/R MZL who had received >=1 line of therapy including >=1 CD20-directed regimen. All were treated with zanubrutinib 160 mg twice daily until disease progression or unacceptable toxicity. Use of long-term antiplatelet and anticoagulation agents was permitted. The primary end point was ORR determined by an independent review committee in accordance with the Lugano classification. Secondary end points include ORR by investigator assessment, duration of response (DOR), progression-free survival (PFS), and safety. Result(s): As of January 11, 2021, 68 pts were enrolled and treated. Median age was 70 years (range, 37-95), with 28% aged >=75 years. Subtypes included extranodal (mucosa-associated lymphoid tissue; 38%), nodal (38%), splenic (18%), and indeterminate (6%) MZL. Median number of prior therapies was 2 (range, 1-6) and 32% of pts had disease that was refractory to last therapy. Median duration of drug exposure was 59.1 weeks (range, 3.

Introduction: Zanubrutinib is a potent, specific next-generation BTK inhibitor with high selectivity for BTK vs the TEC-and EGFR-family kinases, which may be related to off-target toxicities. Method(s): This is a single-arm, multicenter study of adults with R/R MZL who previously received >=1 prior therapy including >=1 CD20 antibody regimen. All received zanubrutinib 160 mg bid until disease progression/unacceptable toxicity. Primary endpoint was overall response rate (ORR) by independent review committee (IRC). Secondary endpoints include investigator-assessed (INV) ORR, duration of response (DOR), progression-free survival (PFS), and safety. Result(s): By January 11, 2021, 68 patients (pts) were enrolled and treated. Median age was 70 years (range, 37-95). Subtypes included extranodal (38%), nodal (38%), splenic (18%), and indeterminate in 6% of pts. Median number of prior therapies was 2 (range, 1-6), and 32% had disease refractory to last therapy. Median duration of drug exposure was 59.1 weeks (range, 3.7-84.1). At a median follow-up of 15.5 months (range, 1.6-21.7), INVORR was 74% with a CR rate of 24%. Responses were observed in all subtypes. Median DOR and PFS were not reached. IRC review is ongoing. Twenty-eight (41%) pts discontinued treatment. The most common treatment-emergent AEs reported in >=10% of pts were diarrhea (22%), bruising (21%), and constipation (15%). Neutropenia was the most common grade >=3 AE (10%). All-grade AEs of interest included neutropenia (13%), thrombocytopenia (13%), atrial fibrillation/flutter (3%), and hypertension (3%). No major/serious hemorrhage was reported. No AEs led to dose reductions. Conclusion(s): Zanubrutinib demonstrated high response rates and durable disease control with a favorable safety profile in pts with R/R MZL. EA-previously submitted to EHA 2021.

Introduction: Zanubrutinib is a potent, specific next-generation BTK inhibitor with high selectivity for BTK vs the TEC-and EGFR-family kinases, which may be related to off-target toxicities. Method(s): This is a single-arm, multicenter study of adults with R/R MZL who previously received >=1 prior therapy including >=1 CD20 antibody regimen. All received zanubrutinib 160 mg bid until disease progression/unacceptable toxicity. Primary endpoint was overall response rate (ORR) by independent review committee (IRC). Secondary endpoints include investigator-assessed (INV) ORR, duration of response (DOR), progression-free survival (PFS), and safety. Result(s): By January 11, 2021, 68 patients (pts) were enrolled and treated. Median age was 70 years (range, 37-95). Subtypes included extranodal (38%), nodal (38%), splenic (18%), and indeterminate in 6% of pts. Median number of prior therapies was 2 (range, 1-6), and 32% had disease refractory to last therapy. Median duration of drug exposure was 59.1 weeks (range, 3.7-84.1). At a median follow-up of 15.5 months (range, 1.6-21.7), INVORR was 74% with a CR rate of 24%. Responses were observed in all subtypes. Median DOR and PFS were not reached. IRC review is ongoing. Twenty-eight (41%) pts discontinued treatment. The most common treatment-emergent AEs reported in >=10% of pts were diarrhea (22%), bruising (21%), and constipation (15%). Neutropenia was the most common grade >=3 AE (10%). All-grade AEs of interest included neutropenia (13%), thrombocytopenia (13%), atrial fibrillation/flutter (3%), and hypertension (3%). No major/serious hemorrhage was reported. No AEs led to dose reductions. Conclusion(s): Zanubrutinib demonstrated high response rates and durable disease control with a favorable safety profile in pts with R/R MZL. EA-previously submitted to EHA 2021.