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A multi-agent experimental combination regimen under clinical investigation for previously untreated aggressive B-cell lymphoma (a-BCL) and large B-cell lymphoma (LBCL), consisting of the novel cereblon E3 ligase modulator CC-99282 (a CELMoD), the antibody-drug conjugate polatuzumab vedotin, and a modified chemotherapy backbone (R-CHP: rituximab, cyclophosphamide, doxorubicin, prednisone). - **CC-99282** is an orally administered small molecule, part of the CELMoD class, which modulates cereblon to induce targeted degradation of Ikaros and Aiolos, transcription factors important in lymphoid malignancies. - **Polatuzumab vedotin** is an antibody-drug conjugate targeting CD79b and delivering the cytotoxic payload monomethyl auristatin E. - **R-CHP** omits vincristine from the standard R-CHOP regimen to avoid overlapping neurotoxicity with polatuzumab. This combination is in early-phase clinical trials for newly diagnosed aggressive B-cell lymphomas, with the aim of improving efficacy over current standards by adding two targeted agents to cytotoxic chemotherapy. Primary indications under investigation are untreated diffuse large B-cell lymphoma (DLBCL), high-grade B-cell lymphoma (HGBL), and related B-cell malignancies[1][4].
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