Low-dose anti-CD20 veltuzumab given intravenously or subcutaneously is active in relapsed immune thrombocytopenia: a phase I study

Br J Haematol. 2013 Sep;162(5):693-701. doi: 10.1111/bjh.12448. Epub 2013 Jul 6.

Abstract

Low doses of the humanized anti-CD20 monoclonal antibody, veltuzumab, were evaluated in 41 patients with immune thrombocytopenia (ITP), including 9 with ITP ≤1 year duration previously treated with steroids and/or immunoglobulins, and 32 with ITP >1 year and additional prior therapies. They received two doses of 80-320 mg veltuzumab 2 weeks apart, initially by intravenous (IV) infusion (N = 7), or later by subcutaneous (SC) injections (N = 34), with only one Grade 3 infusion reaction and no other safety issues. Thirty-eight response-assessable patients had 21 (55%) objective responses (platelet count ≥30 × 10(9) /l and ≥2 × baseline), including 11 (29%) complete responses (CRs) (platelet count ≥100 × 10(9) /l). Responses (including CRs) occurred with both IV and SC administration, at all veltuzumab dose levels, and regardless of ITP duration. Responders with ITP ≤1 year had a longer median time to relapse (14·4 months) than those with ITP >1 year (5·8 months). Three patients have maintained a response for up to 4·3 years. SC injections resulted in delayed and lower peak serum levels of veltuzumab, but B-cell depletion occurred after first administration even at the lowest doses. Eight patients, including 6 responders, developed anti-veltuzumab antibodies following treatment (human anti-veltuzumab antibody, 19·5%). Low-dose SC veltuzumab appears convenient, well-tolerated, and with promising clinical activity in relapsed ITP.(Clinicaltrials.gov identifier: NCT00547066.).

Keywords: CD20; ITP; antibody; hA20; immune thrombocytopenia; subcutaneous therapy.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / blood
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Antigens, CD20 / immunology
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Humans
  • Infusions, Intravenous
  • Injections, Subcutaneous
  • Male
  • Middle Aged
  • Purpura, Thrombocytopenic, Idiopathic / blood
  • Purpura, Thrombocytopenic, Idiopathic / drug therapy*
  • Recurrence
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Antigens, CD20
  • veltuzumab

Associated data

  • ClinicalTrials.gov/NCT00547066