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December 8, 2025BloodOpen Access

Impact of prognostic mutations on outcomes with fixed-duration acalabrutinib-venetoclax combinations versus chemoimmunotherapy: An exploratory analysis from AMPLIFY

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Authors

AFAna Rita Da FonsecaDCDennis CarneyDSDon A. Stevens

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Overview

Exploratory analysis shows improvements in progression-free survival for venetoclax in chronic lymphocytic leukemia, indicating genetic factors influence treatment outcomes.

Key Points

  • This analysis explores the impact of prognostic mutations on treatment outcomes in patients with chronic lymphocytic leukemia receiving targeted therapies.
  • Ongoing randomized phase 3 trial of patients with treatment-naive chronic lymphocytic leukemia aged ≥18.
  • Patients received acalabrutinib plus venetoclax or chemoimmunotherapy.
  • Genetic factors analyzed through next-generation sequencing, focusing on specific mutations.
  • Prolonged progression-free survival observed with acalabrutinib-venetoclax compared to chemoimmunotherapy.
  • Mutation analysis showed interactions between genetic factors and treatment outcomes.
  • Significant differences in outcomes based on IGHV mutation status and specific gene mutations.

Cite This Study

Fonseca et al. (2025) studied this question.

synapsesocial.com/papers/69362f714fa91c937236e21chttps://doi.org/10.1182/blood-2025-3898
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Mutation-guided finite-duration acalabrutinib plus venetoclax for relapse after first-line finite-duration COVALENT Bruton tyrosine kinase inhibitor plus venetoclax‒based combination therapy in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma: Phase 2 MAVRiC study2025
  2. 2Addition of obinutuzumab after one year of combined acalabrutinib and venetoclax is safer and effective than early obinutuzumab in a randomized Phase II trial for treatment naïve CLL2025 · 3 citations
  3. 3Phase I/II study of acalabrutinib, venetoclax, and obinutuzumab in patients with relapsed/refractory and previously untreated Mantle Cell Lymphoma (MAVO)2025 · 8 citations
  4. 4MRD-guided ibrutinib plus venetoclax improves outcomes in CLL patients with TP53, ATM, or NOTCH1 aberrations compared to ibrutinib and FCR: Results from the Phase III NCRI FLAIR trial2025 · 1 citations
  5. 5Upfront continuous BTK inhibitor (BTKi) versus time-limited venetoclax-BTKi combinations in CLL across IGHV subgroups: Results of an indirect analysis2025