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The **tirabrutinib + idelalisib + obinutuzumab** combination, also referred to as the TIO regimen, consists of three agents with complementary mechanisms of action, used primarily in the treatment of relapsed or refractory chronic lymphocytic leukemia (CLL). Tirabrutinib is a selective, irreversible, second-generation small molecule inhibitor of Bruton’s tyrosine kinase (BTK), impairing B-cell receptor signaling and reducing proliferation of malignant B cells. Idelalisib is a phosphatidylinositol 3-kinase delta (PI3Kδ) inhibitor, disrupting downstream signaling essential for B-cell survival and migration. Obinutuzumab is a humanized type II anti-CD20 monoclonal antibody that induces B-cell lysis via direct cytotoxicity and immune-mediated mechanisms. The combination is designed to deepen and prolong responses compared to monotherapy, though it is associated with notable toxicities such as infections and cytopenias.
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