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Ref Type Journal Article
PMID (25754579)
Authors Martin P, Furman RR, Rutherford S, Ruan J, Ely S, Greenberg J, Coleman M, Goldsmith SJ, Leonard JP
Title Phase I study of the anti-CD74 monoclonal antibody milatuzumab (hLL1) in patients with previously treated B-cell lymphomas.
Journal Leukemia & lymphoma
Vol 56
Issue 11
Date 2015
URL
Abstract Text 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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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Milatuzumab Milatuzumab 2 0
Drug Name Trade Name Synonyms Drug Classes Drug Description
Milatuzumab IMMU-115|hLL1 CD74 Antibody 3 Milatuzumab (IMMU-115) is a monocloncal antibody to CD74 that induces apoptosis and targets tumor cells with high CD74 expression, such as B-cells (PMID: 25754579, PMID: 28466956).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown hematologic cancer no benefit Milatuzumab Phase I Actionable In a Phase I trial, Milatuzumab (hLL1) treatment of a mixed cohort of B-cell malignancies patients, resulted in stable disease in 35% (8/23), but there was no evidence of tumor shrinkage (PMID: 25754579). 25754579