Safety and efficacy of zanubrutinib in patients with relapsed/refractory marginal zone lymphoma (magnolia phase 2 study).

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.