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Epcoritamab + ibrutinib + lenalidomide is an investigational combination therapy evaluated for the treatment of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) and other B-cell non-Hodgkin lymphomas. **Epcoritamab** is a bispecific monoclonal antibody that binds CD3 on T cells and CD20 on B cells, redirecting T cells to kill CD20+ B cells. **Ibrutinib** is a small molecule inhibitor of Bruton tyrosine kinase (BTK), which impairs B-cell receptor signaling and inhibits lymphoma cell survival. **Lenalidomide** is an immunomodulatory agent with anti-neoplastic, anti-angiogenic, and immune-activating properties, including effects on T cells and NK cells. The combination aims to enhance antitumor activity through complementary mechanisms involving B-cell targeting, immune cell activation, and disruption of B-cell proliferation signals. Early stage clinical trials (such as EPCORE NHL-5) are evaluating the safety, tolerability, and efficacy of this triplet in relapsed/refractory DLBCL[1][5][7].
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