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Odronextamab + zanubrutinib is a combination therapy being investigated for the treatment of Richter's transformation (RT). Odronextamab (Ordspono) is a bispecific monoclonal antibody that targets CD20 on B cells and CD3 on T cells, facilitating T-cell mediated destruction of malignant B cells. Zanubrutinib (Brukinsa) is a potent, selective, and irreversible small-molecule inhibitor of Bruton tyrosine kinase (BTK), which plays a crucial role in B-cell receptor signaling. The combination is currently being evaluated in a Phase I clinical trial led by City of Hope Medical Center to assess its safety and efficacy in patients with RT, a rare and aggressive transformation of chronic lymphocytic leukemia into high-grade lymphoma. This therapeutic approach aims to leverage both direct B-cell receptor pathway inhibition and immune-mediated cytotoxicity to overcome the aggressive nature of transformed lymphoma.
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