Matching‐adjusted indirect comparison (MAIC) of zanubrutinib (ZANU) versus ibrutinib (IBRU) in relapsed/refractory marginal zone lymphoma (R/R MZL)
Bibliographic record
Abstract
Introduction: ZANU is a Bruton tyrosine kinase inhibitor (BTKi) that has been evaluated for the treatment of R/R MZL in two phase 2, single-arm trials (MAGNOLIA, n = 66, NCT03846427; BGB-3111-AU-003, n = 20, NCT02343120). At 28 and 35 months of study follow-up in MAGNOLIA and BGB-3111-AU-003, respectively, median progression-free survival (PFS) and overall survival (OS) were not reached. IBRU, a first-generation BTKi, has also been evaluated for R/R MZL in a phase 2, single-arm trial (PCYC-1121, n = 60 [Noy et al. Blood 2017; Noy et al. Blood Adv 2020]). Here, we conducted an unanchored MAIC to estimate the comparative efficacy of ZANU versus IBRU in R/R MZL. Methods: The MAIC utilized study-level data from PCYC-1121 and pooled individual patient-level data from MAGNOLIA and BGB-3111-AU-003. A logistic propensity score model (PSM) was used to estimate weights for patients in the ZANU trials so that weighted mean baseline characteristics matched those in PCYC-1121. Number of prior lines of therapy, MZL subtype, response to prior therapy, and age were identified as key prognostic factors and included in the base case PSM. A sensitivity analysis was conducted including additional characteristics (B symptoms, time since last therapy, prior anti-CD20 therapy, bulky disease [>5 cm], and lactate dehydrogenase above normal). Comparisons were conducted for OS, PFS, and objective response rate (ORR) by independent review committee using weighted statistical models with relative treatment effects presented as hazard ratios (HRs), odds ratios (ORs), and 95% confidence intervals (CIs). Results: After applying weights estimated from the base case PSM, the effective sample size (ESS) for ZANU was 68 (Table). Compared with IBRU, ZANU significantly reduced the risk of progression (HR 0.38; 95% CI: 0.21, 0.69; p = 0.001) and was associated with a higher ORR (OR 2.37; 95% CI: 1.13, 4.96; p = 0.022). OS was comparable for ZANU and IBRU, which is consistent with expected survival for indolent lymphomas. The sensitivity analysis accounting for additional prognostic factors suggested the 2 treatments were comparable across all outcomes, owing in part to the low ESS (24) for ZANU associated with the expanded model. A leave-one-out analysis showed improved PFS (HR 0.33–0.45) for ZANU when excluding B symptoms, time since last therapy, or bulky disease from the expanded model. Conclusions: This MAIC demonstrated ORR and PFS benefits for ZANU versus IBRU in R/R MZL. Encore Abstract - previously submitted to ASCO 2023 and EHA 2023 The research was funded by: BeiGene Keywords: Indolent non-Hodgkin lymphoma, Molecular Targeted Therapies Conflicts of interests pertinent to the abstract. C. Thieblemont Honoraria: AbbVie, Bayer, Celgene, Gilead Sciences, Incyte, Janssen, Novartis, and Roche Research funding: Roche Educational grants: AbbVie, Janssen-Cilag, Kite/Gilead, Novartis, and Roche S. Keeping Employment or leadership position: PRECISIONheor Research funding: BeiGene I. Zhang Employment or leadership position: PRECISIONheor Research funding: BeiGene K. Yang Employment or leadership position: BeiGene Stock ownership: BeiGene Research funding: BeiGene Educational grants: BeiGene B. Tang Employment or leadership position: BeiGene Stock ownership: BeiGene Other remuneration: BeiGene L. Mohseninejad Employment or leadership position: BeiGene Consultant or advisory role: BeiGene Research funding: BeiGene
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".