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.