pomalidomide + rituximab + orelabrutinib + polatuzumab vedotin

This is an investigational, chemotherapy‑free quadruple regimen combining the immunomodulatory agent pomalidomide, the anti‑CD20 monoclonal antibody rituximab, the covalent Bruton tyrosine kinase (BTK) inhibitor orelabrutinib, and the CD79b‑targeted antibody‑drug conjugate polatuzumab vedotin, being explored for B‑cell malignancies such as diffuse large B‑cell lymphoma and primary central nervous system lymphoma. Pomalidomide enhances anti‑tumor immunity and exerts direct anti‑myeloma/lymphoma effects via cereblon‑mediated degradation of transcription factors; rituximab depletes CD20‑positive B cells through complement‑dependent cytotoxicity, antibody‑dependent cellular cytotoxicity, and apoptosis; orelabrutinib blocks B‑cell receptor signaling by irreversibly inhibiting BTK; and polatuzumab vedotin delivers the microtubule‑disrupting payload monomethyl auristatin E to CD79b‑expressing B cells, leading to targeted cytotoxicity. Together, these agents provide complementary immune, signaling, and cytotoxic mechanisms intended to improve responses in relapsed or refractory B‑cell lymphomas while reducing reliance on conventional chemotherapy.[3][8]