Pirtobrutinib

Non-covalent (reversible) BTK inhibitor

Response rate
~68% ORR (after covalent BTKi); 56% VGPR with venetoclax combo
Onset
Weeks
Route
Oral 200mg daily
Line
2nd
IgM effect
Reduction

Evidence summary

Non-covalent BTK inhibitor that retains activity after covalent BTK inhibitor resistance or intolerance. Being studied in combination with venetoclax (pirtobrutinib + venetoclax: 100% ORR, 56% VGPR in interim analysis). May overcome acquired BTK C481S resistance mutations.

Molecular targets (1)

MoleculeRoleExpressionEvidence
BTK (Bruton's Tyrosine Kinase)Key signaling kinase downstream of MYD88Constitutively activatedestablished

Sources (1)

DetailsGertz MA (2025) WM: 2025 update on diagnosis, risk stratification, and management · Am J HematolDOI