polatuzumab vedotin + acalabrutinib + rituximab + lenalidomide

This is an investigational, chemotherapy‑free quadruple regimen combining the CD79b‑targeted antibody‑drug conjugate polatuzumab vedotin, the covalent Bruton tyrosine kinase (BTK) inhibitor acalabrutinib, the CD20‑directed chimeric monoclonal antibody rituximab, and the immunomodulatory small molecule lenalidomide for B‑cell non‑Hodgkin lymphomas such as diffuse large B‑cell lymphoma (DLBCL). Polatuzumab vedotin delivers the microtubule‑disrupting payload monomethyl auristatin E (MMAE) to CD79b‑expressing B cells, acalabrutinib blocks B‑cell receptor signaling via BTK, rituximab mediates B‑cell depletion through CD20 targeting and immune effector mechanisms, and lenalidomide enhances antitumor immunity and has direct antiproliferative effects on malignant B cells. The biological rationale of this combination is to synergistically target B‑cell receptor signaling, surface antigens, and the tumor microenvironment without conventional cytotoxic chemotherapy.