Intravenous low-dose anti-CD20 Rituximab infusion contrasted with subsequent subcutaneous Rituximab injection during CLL patient treatment 3374

Abstract Description We evaluated high frequency (2/week) low dose (50 mg) (HFLD) anti-CD20 monoclonal antibody (mAb), rituximab (RTX), during treatment of progressive CLL patients (PMID 36689726). The initial RTX dose was by intravenous (IV) infusion to monitor for potential reactions. Subsequent RTX doses were by subcutaneous (SQ) injection to reduce clinical monitoring and allow home administration. Blood specimens were collected during the first week of therapy: before IV infusion, 1h during, after infusion completion, 48h later (before and after first SQ injection), and 7 days later (before next RTX injection). The initial IV RTX decreased the median circulating CLL cell count by 84% from baseline. Maximal depletion of CLL cells was rapid and complete within 1h of starting RTX infusion. In contrast, CLL CD20 levels continue to decline at the end of infusion. Mobilization of CLL cells was evidenced by a partial rebound in CLL cell counts and CD20 levels after 48h and 7 days. SQ RTX injection adds complexity to data interpretation because of delayed RTX entry into circulation, resulting in delayed RTX serum level kinetics compared to IV infusion. Our data suggest slow SQ mAb diffusion into circulation steadily binds to CLL cells, resulting in low serum levels and slow depletion of CLL cells, with increasing serum RTX levels as SQ doses accumulate. Surviving CLL cells were still sensitive to mAb cytotoxicity, suggesting that cytotoxic effector cells were “exhausted” by RTX therapy. Funding Sources We are grateful for research funding from the NCI (R21CA267040), Acerta/AstraZeneca, the Cadregari Foundation at the University of Rochester, generous gifts from Mr. Lawrence Halpern, and generous gifts from Ms. Elizabeth Aaron. Topic Categories Translational and Interventional Immunology (TI)