Phase I, multicentre, dose-escalation trial of monotherapy with milatuzumab (humanized anti-CD74 monoclonal antibody) in relapsed or refractory multiple myeloma

Br J Haematol. 2013 Nov;163(4):478-86. doi: 10.1111/bjh.12565. Epub 2013 Sep 25.


CD74, expressed in multiple myeloma (MM), was evaluated as a target for immunotherapy with milatuzumab (a humanized anti-CD74 antibody). In a multicentre dose escalation study, 25 patients with advanced MM received milatuzumab doses of 1.5 (N = 8), 4.0 (N = 9), 8.0 (N = 4) or 16.0 mg/kg (N = 4) administered twice weekly x 4. They had a median of 5 prior treatments (17 post ≥ 1 stem cell transplantation) and were refractory (N = 7) or relapsed (N = 18) with generally short-lived responses to last treatment (median 4.0 months). After increasing prophylactic medications and slowing administration, infusions were well tolerated (National Cancer Institute-Common Terminology Criteria v3 toxicity Grades 1-2) with no dose-limiting toxicity at higher doses. Only one patient developed borderline positive human anti-milatuzumab antibody titres of uncertain clinical significance. Although milatuzumab was rapidly cleared from circulation with little serum accumulation and low trough levels, B-cell levels were moderately decreased with treatment (median decrease, 34%). There were no objective responses by European Group for Blood and Marrow Transplantation criteria, but 5 of 19 patients (26%) who completed treatment in this heavily pretreated and generally refractory group had stable disease for ≥ 3 months post-treatment (one continuing for 17 months). Disease stabilization and evidence of pharmacodynamic activity support further development for use in combination with other agents or as a drug conjugate.

Trial registration: NCT00421525.

Keywords: CD74; antibody; milatuzumab; multiple myeloma; phase 1 clinical trial.

Publication types

  • Clinical Trial, Phase I
  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Antibodies, Monoclonal, Humanized / adverse effects
  • Antibodies, Monoclonal, Humanized / pharmacokinetics
  • Antigens, Differentiation, B-Lymphocyte / immunology
  • Dose-Response Relationship, Drug
  • Female
  • Histocompatibility Antigens Class II / immunology
  • Humans
  • Male
  • Middle Aged
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / metabolism
  • Recurrence


  • Antibodies, Monoclonal, Humanized
  • Antigens, Differentiation, B-Lymphocyte
  • Histocompatibility Antigens Class II
  • invariant chain
  • milatuzumab

Associated data