title: Comparison of two dosing schedules for subcutaneous injections of low-dose anti-CD20 veltuzumab in relapsed immune thrombocytopenia.
abstract: We compared two dosing schedules for subcutaneous injections of a low-dose humanized anti-CD20 antibody, veltuzumab, in immune thrombocytopenia. Fifty adults with primary immune thrombocytopenia, in whom one or more lines of standard therapy had failed and who had a platelet count <30×109/L but no major bleeding, initially received escalating 80, 160, or 320 mg doses of subcutaneous veltuzumab administered twice, 2 weeks apart; the last group received once-weekly doses of 320 mg for 4 weeks. In all dose groups, injection reactions were transient and mild to moderate; there were no other safety issues. Forty-seven response-evaluable patients had 23 (49%) objective responses (platelet counts ≥30×109/L and ≥2 × baseline) including 15 (32%) complete responses (platelets ≥100×109/L). Responses (including complete responses) and bleeding reduction occurred in all dose groups and were not dose-dependent. In contrast, response duration increased progressively with total dose, reaching a median of 2.7 years with the four once-weekly 320-mg doses. Among nine responders retreated at relapse, three at higher dose levels responded again, including one patient who was retreated four times. In all dose groups, B-cell depletion occurred after the first dose until recovery starting 12 to 16 weeks after treatment. Veltuzumab serum levels increased with dose group according to total dose administered, but terminal half-life and clearance were comparable. Human anti-veltuzumab antibody titers developed without apparent dose dependence in nine patients, of whom six responded including five who had complete responses. Subcutaneous veltuzumab was convenient, well-tolerated, and active, without causing significant safety concerns. Platelet responses and bleeding reduction occurred in all dose groups, and response durability appeared to improve with higher doses. Clinicaltrials.gov identifier: NCT00547066.
authors: Internal Medicine, Jane Anne Nohl Division of Hematology, Keck School of Medicine of University of Southern California, Los Angeles, CA, USA liebman@usc.edu dmg.gscancer@att.net.
authors: Howard A
authors: HA
authors: Liebman
authors: Georgia Cancer Specialists, Atlanta, GA, USA.
authors: Mansoor N
authors: MN
authors: Saleh
authors: Platelet Disorders Center, Division of Pediatric Hematology-Oncology, New York Presbyterian Hospital, NY, USA.
authors: James B
authors: JB
authors: Bussel
authors: Low Country Cancer Care Assoc., Savannah, GA, USA.
authors: O George
authors: OG
authors: Negrea
authors: Immunomedics, Inc., Morris Plains, NJ, USA.
authors: Heather
authors: H
authors: Horne
authors: Immunomedics, Inc., Morris Plains, NJ, USA.
authors: William A
authors: WA
authors: Wegener
authors: Immunomedics, Inc., Morris Plains, NJ, USA liebman@usc.edu dmg.gscancer@att.net.
authors: David M
authors: DM
authors: Goldenberg
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage* / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D012008:Recurrence; D012074:Remission Induction; D013921:Thrombocytopenia / Q000188:drug therapy* / Q000276:immunology
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C493846:veltuzumab