Pirtobrutinib: First Non-covalent Tyrosine Kinase Inhibitor for Treating Relapsed or Refractory Mantle Cell Lymphoma in Adults

Mantle Cell Lymphoma (MCL) is an aggressive subtype of Non-hodgkin's Lymphoma (NHL). Bruton Tyrosine Kinase (BTK) is a non-receptor tyrosine kinase, and is one of the therapeutic targets for B-cell-driven malignancies. Approved covalent BTK inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib are associated with treatment limitations due to off-target side effects and the development of C481 substitution resistance mutations. Pirtobrutinib was approved by the US FDA on January 27, 2023, for the treatment of relapsed or refractory mantle cell lymphoma, including the resistance to covalent BTK inhibitors. In this perspective, physicochemical properties, synthesis, dosage and administration, mechanism of action, pharmacodynamics, pharmacokinetics, drug interactions, and treatment-emergent adverse events of pirtobrutinib are discussed.