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

Abstract

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.

• Authors: Jonathan L Kaufman, Ruben Niesvizky, Edward A Stadtmauer, Asher Chanan-Khan, David Siegel, Heather Horne, William A Wegener, David M Goldenberg
• Journal: British journal of haematology (Br J Haematol) Vol. 163 Issue 4 Pg. 478-86 (Nov 2013) ISSN: 1365-2141 [Electronic] England
• PMID: 24112026 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study)
• Copyright: © 2013 John Wiley & Sons Ltd.

Chemical References

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

Topics

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