Pirtobrutinib for the Treatment of Therapy‐Resistant Chronic Lymphatic Leukemia With CNS Localization

During the last decade, many new treatment options for chronic lymphatic leukemia (CLL) have become available, one of them being covalent‐binding Bruton’s tyrosine kinase inhibitors (cBTK inhibitors [cBTKis]). There are currently three cBTKis approved for treatment of CLL/SLL: acalabrutinib, ibrutinib, and zanubrutinib. In relapsed and heavily pretreated patients, BTK inhibitors achieve a median PFS of 4 years, and in frontline, around 80% of CLL patients are still in remission and alive after 4 years of treatment with BTK inhibitors. Despite their efficacy, 40% of patients have to discontinue BTK inhibitors because of side effects or treatment resistance. We present the efficacy of the novel noncovalent BTKi in a patient with CLL who developed covalent BTKi‐resistant disease with CNS localization. Pirtobrutinib appears to be effective in patients with ibrutinib resistance, even with CNS localization. Clinical responses may take several months to become evident.