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**ibrutinib + fludarabine + cyclophosphamide + rituximab** (abbreviated as iFCR) is an investigational combination regimen used for the treatment of **chronic lymphocytic leukemia (CLL)**, particularly in younger, fit, previously untreated patients. The regimen combines: - **ibrutinib**, a first-in-class, irreversible, oral small molecule inhibitor of Bruton tyrosine kinase (BTK), which disrupts B-cell receptor signaling; - **fludarabine** and **cyclophosphamide**, both cytotoxic chemotherapeutic agents—fludarabine is a purine analogue that interferes with DNA synthesis and cyclophosphamide is an alkylating agent causing cross-linking of DNA strands; - **rituximab**, a monoclonal antibody that targets CD20 on B-lymphocytes, leading to their destruction. The combined regimen is designed to increase the depth and durability of response compared to conventional chemoimmunotherapy (FCR). In the phase 2 trial, induction involves ibrutinib lead-in followed by up to six cycles of all four agents, with maintenance ibrutinib afterwards. This approach is under clinical investigation and is not approved as a standard of care but is being explored as a potential curative approach in CLL[2].
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