How I use genomics and BTK inhibitors in the treatment of Waldenström macroglobulinemia.
Blood
; 143(17): 1702-1712, 2024 Apr 25.
Article
in En
| MEDLINE
| ID: mdl-38211337
ABSTRACT
ABSTRACT Mutations in MYD88 (95%-97%) and CXCR4 (30%-40%) are common in Waldenström macroglobulinemia (WM). TP53 is altered in 20% to 30% of patients with WM, particularly those previously treated. Mutated MYD88 activates hematopoietic cell kinase that drives Bruton tyrosine kinase (BTK) prosurvival signaling. Both nonsense and frameshift CXCR4 mutations occur in WM. Nonsense variants show greater resistance to BTK inhibitors. Covalent BTK inhibitors (cBTKi) produce major responses in 70% to 80% of patients with WM. MYD88 and CXCR4 mutation status can affect time to major response, depth of response, and/or progression-free survival (PFS) in patients with WM treated with cBTKi. The cBTKi zanubrutinib shows greater response activity and/or improved PFS in patients with WM with wild-type MYD88, mutated CXCR4, or altered TP53. Risks for adverse events, including atrial fibrillation, bleeding diathesis, and neutropenia can differ based on which BTKi is used in WM. Intolerance is also common with cBTKi, and dose reduction or switchover to another cBTKi can be considered. For patients with acquired resistance to cBTKis, newer options include pirtobrutinib or venetoclax. Combinations of BTKis with chemoimmunotherapy, CXCR4, and BCL2 antagonists are discussed. Algorithms for positioning BTKis in treatment naïve or previously treated patients with WM, based on genomics, disease characteristics, and comorbidities, are presented.
Full text:
1
Database:
MEDLINE
Main subject:
Waldenstrom Macroglobulinemia
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Protein Kinase Inhibitors
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Agammaglobulinaemia Tyrosine Kinase
Limits:
Adult
/
Aged
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Female
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Humans
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Male
/
Middle aged
Language:
En
Journal:
Blood
Year:
2024
Type:
Article
Affiliation country:
Morocco