Anchored Analysis Comparing Zanubrutinib with Acalabrutinib-Venetoclax

Dr. Brander introduces the third analysis comparing zanubrutinib from SEQUOIA with acalabrutinib plus venetoclax from AMPLIFY, representing an anchored analysis with similar comparison arms showing zanubrutinib association with prolonged progression-free survival when adjusting for baseline characteristics. Dr. Shadman explains the analysis timing relevance, comparing zanubrutinib as a preferred BTK inhibitor against newly approved acalabrutinib-venetoclax combination, addressing patient preferences for efficacy-focused treatment selection.

The anchored MIAC methodology utilizes shared control arms between studies: SEQUOIA compared zanubrutinib versus bendamustine-rituximab, whereas AMPLIFY compared acalabrutinib-venetoclax versus fludarabine-cyclophosphamide-rituximab or bendamustine-rituximab. The shared bendamustine-rituximab control arm enables anchored analysis with internal validity checking through control arm outcome comparisons. Regulatory bodies outside the United States place higher value on anchored versus unanchored analyses due to this internal validation capability.

Different patient populations required adjustment, as AMPLIFY included fludarabine-cyclophosphamide-rituximab controls selecting healthier, younger, fit patients, whereas SEQUOIA used bendamustine-rituximab selecting different populations. Adjustment occurred through MIAC methodology and selecting patients meeting AMPLIFY inclusion criteria from SEQUOIA patient-level data. Results showed numerically greater 3-year investigator-assessed progression-free survival with zanubrutinib versus acalabrutinib-venetoclax, with more pronounced differences (89% versus 78%) when matching SEQUOIA patients eligible for fludarabine-cyclophosphamide-rituximab in AMPLIFY. Dr. Shadman emphasizes these analyses provide important information for efficacy-focused patients prioritizing longer remission over treatment-free periods, representing a significant patient proportion in clinical practice.