Matching-Adjusted Indirect Comparison (MAIC) of Zanubru�nib Versus Real-World
Chemoimmunotherapy (CIT) or Chemotherapy (Chemo) in Relapsed/Refractory Marginal Zone
Lymphoma (R/R MZL)
Renata Walewska*1, Kaijun Wang2, Caitlin Smare3, Ina Zhang4, Leyla Mohseninejad5, Silvy Mardiguian6,Sam Keeping7
1University Hospitals Dorset, Department of Haematology, Bournemouth, United Kingdom, 2BeiGene

USA, Inc., San Mateo, CA, United States of America, 3PRECISIONheor, London, United Kingdom,

4PRECISIONheor, Oakland, CA, United States of America, 5BeiGene Netherlands B.V., Schiphol, TheNetherlands, 6BeiGene, London, United Kingdom, 7PRECISIONheor, Vancouver, British Columbia, Canada

Background: MZL is a rare indolent form of non-Hodgkin lymphoma, with high morbidity and decreased
quality of life associated with relapsed disease. Zanubru�nib is a next genera�on Bruton tyrosine kinase
inhibitor that has been approved for the treatment of R/R MZL in the EU and UK based on two phase 2,
single-arm trials (MAGNOLIA, n=66, NCT03846427; BGB-3111-AU-003, n=20, NCT02343120). At 28 and35 months of study follow-up in MAGNOLIA and BGB-3111-AU-003, respec�vely, median progressionfree survival (PFS) and overall survival (OS) were not reached. While no standard of care currently exists
for pa�ents with R/R MZL, a repe��on of rituximab-based CIT or chemo is recommended by clinicalguidelines. To beter understand the rela�ve treatment eﬀects of zanubru�nib and CIT or chemo, acohort representa�ve of the pa�ents included in the zanubru�nib trials was iden�ﬁed from a United
Kingdom (UK) registry, the Haematological Malignancy Research Network (HMRN).
Aims: An unanchored MAIC was conducted to es�mate the compara�ve eﬀec�veness of zanubru�nibversus CIT or chemo in R/R MZL.
Methods: The MAIC u�lized aggregate data from HMRN and pooled individual pa�ent-level data fromMAGNOLIA and BGB-3111-AU-003 (MAGNOLIA-003 herea�er). Real-world evidence on the eﬀec�venessof CIT or chemo was based on a cohort of the HMRN registry constructed to resemble the pa�ents
included in MAGNOLIA-003. Overall, the HMRN cohort selected for analysis consisted of 90 pa�ents who
were enrolled from 2014 onwards, with an ECOG performance status ≤2 at this �me, and who received
CIT or chemo a�er having previously received at least one an�-CD20-based therapy. A logis�cpropensity score model was applied to es�mate weights for pa�ents in MAGNOLIA-003 such thatweighted mean baseline characteris�cs matched those in the HMRN dataset. The following
characteris�cs were pre-speciﬁed as key prognos�c factors and considered for adjustment in the basecase model: number of prior lines of therapy, refractory to prior therapy, age, progression of disease
within 24 months of ini�a�on of systemic therapy, and median �me since diagnosis. Comparisons wereconducted for PFS and OS. Rela�ve treatment eﬀects were es�mated from Cox models and presented ashazard ra�os (HRs) and 95% conﬁdence intervals (CIs). A sensi�vity analysis focused on old/frail pa�ents
receiving CIT only was also performed. Leave-one-out analyses were performed, whereby one covariate
was omited from the model at a �me to explore the impact of each covariate on the model results.
Results: A�er applying weights es�mated from the base case model, the eﬀec�ve sample size (ESS) for
MAGNOLIA-003 was 38. Compared with CIT or chemo, zanubru�nib signiﬁcantly reduced the risk ofprogression (HR 0.30; 95% CI 0.15–0.63, p=0.001) and death (HR 0.23; 95% CI 0.10–0.50, p<0.001)(Figure). The sensi�vity analysis comparison of zanubru�nib (ESS=40) to CIT also demonstrated
signiﬁcantly reduced risk of progression (HR: 0.28; 95% CI 0.14-0.57, p<0.001) and death (HR: 0.23, 95%

EHA 2024

CI 0.10-0.49, p<0.001). The leave-one-out analyses demonstrated comparable point es�mates andsimilar paterns of signiﬁcance in rela�ve eﬀect es�mates to the base case model.
Summary/Conclusion: This MAIC demonstrated signiﬁcant PFS and OS beneﬁts for zanubru�nib over CITor chemo in R/R MZL.

EHA 2024