Phase I study of the anti-CD74 monoclonal antibody milatuzumab (hLL1) in patients with previously treated B-cell lymphomas

Leukemia & Lymphoma
Peter MartinJohn P Leonard

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.

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Citations

Oct 19, 2016·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Huiting SuYong Zhao
Feb 22, 2017·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yi ZhouGuo-Ping Shi
Sep 8, 2018·The Journal of Pathology. Clinical Research·Shuchun ZhaoYasodha Natkunam
Feb 7, 2018·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Amanda SparkesBenoît Stijlemans
Jun 21, 2018·PloS One·Lara Valiño-RivasMaria Dolores Sanchez-Niño
Feb 26, 2019·Frontiers in Immunology·Smita Y PatelStephen Jolles
Jun 20, 2020·Journal of Hematology & Oncology·Walter Hanel, Narendranath Epperla
Aug 16, 2021·The Journal of Biological Chemistry·Benjamin SchoepsAchim Krüger

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