Refractory CD20 Research Articles

Rationale and feasibility of combined radiotherapy and Anti-CD20 immunotherapy in CD20+ B cell NHL

Purpose/Objective: “Zevalin” (Ibritumomab Tiuxetan incorporating the beta emitter Y-90) recently became the first radiolabeled antibody compound to receive FDA approval for clinical use against relapsed and refractory low grade CD20+ B cell lymphoma. Dose limiting toxicity for “Zevalin” involves hemopoietic suppression and thrombocytopenia, making depressed marrow reserves an important factor in appropriate patient selection. Mechanisms by which antibody targeting and CD20 surface antigen expression could be further amplified would be of great interest and would potentially allow groups of currently ineligible patients to receive this treatment at lower but still effective doses. Our laboratory group recently reported that relatively low doses of ionizing radiation appear to upregulate CD20 surface antigen expression in a variety of human B cell lines. This observation suggests a possible role for adjunctive low dose radiation targeted to lymphoma deposits using either external beam radiotherapy or low dose RIT delivered in a time-frame calculated to promote targeting efficiency of subsequent CD20+ NHL immunotherapy. In order to establish baseline data on clinical safety and effectiveness of combinations of ionizing radiation and RIT, we have utilized database information on patients registered on “Zevalin” clinical trials who had previously received external beam radiotherapy.