Phase i study of the anti-CD74 monoclonal antibody milatuzumab (hLL1) in patients with previously treated B-cell lymphomas Academic Article uri icon

Overview

MeSH Major

  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Lymphoma, B-Cell

abstract

  • Milatuzumab (hLL1), a humanized anti-CD74 monoclonal antibody, has activity in preclinical non-Hodgkin lymphoma (NHL) models. We conducted a phase 1 trial in previously treated B-cell malignancies. Dose escalation included four planned dose levels (1.5, 4, 6 and 8 mg/kg) with milatuzumab given twice weekly for 6 weeks. After dose level 1, the schedule was changed to daily (Monday-Friday) for 10 days. Twenty-two patients were treated. The most common possibly related toxicities were infusion reaction, anemia, lymphopenia, neutropenia and thrombocytopenia. Three patients experienced dose-limiting toxicity (neutropenia, neutropenia, rash) at dose levels 1, 2 and 4, respectively. Eight patients had stable disease, with no objective responses. The serum half-life of milatuzumab was ∼2 h. In seven patients, In-111 imaging showed no clear evidence of tumor targeting. The short half-life may reflect CD74 rapid internalization and presence on extratumoral tissues; this antigen sink must be overcome to capitalize on the promising preclinical activity of the drug.

publication date

  • January 2015

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC4855286

Digital Object Identifier (DOI)

  • 10.3109/10428194.2015.1028052

PubMed ID

  • 25754579

Additional Document Info

start page

  • 3065

end page

  • 70

volume

  • 56

number

  • 11