title: Phase I study of the anti-CD74 monoclonal antibody milatuzumab (hLL1) in patients with previously treated B-cell lymphomas.
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.
authors.affiliation: a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Martin
authors.affiliation: a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
authors.forename: Richard R
authors.initials: RR
authors.lastname: Furman
authors.affiliation: a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
authors.forename: Sarah
authors.initials: S
authors.lastname: Rutherford
authors.affiliation: a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
authors.forename: Jia
authors.initials: J
authors.lastname: Ruan
authors.affiliation: b Pathology and Laboratory Medicine, Weill Cornell Medical College , New York , NY , USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Ely
authors.affiliation: a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
authors.forename: June
authors.initials: J
authors.lastname: Greenberg
authors.affiliation: a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
authors.forename: Morton
authors.initials: M
authors.lastname: Coleman
authors.affiliation: c Department of Radiology , Weill Cornell Medical College , New York , NY , USA.
authors.forename: Stanley J
authors.initials: SJ
authors.lastname: Goldsmith
authors.affiliation: a Department of Medicine , Weill Cornell Medical College , New York , NY , USA.
authors.forename: John P
authors.initials: JP
authors.lastname: Leonard
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000494:pharmacology / Q000627:therapeutic use*; D000944:Antigens, Differentiation, B-Lymphocyte / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000175:diagnosis / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D012008:Recurrence; D019233:Retreatment; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000944:Antigens, Differentiation, B-Lymphocyte; D000970:Antineoplastic Agents; D015415:Biomarkers; D000949:Histocompatibility Antigens Class II; C045084:invariant chain; C540932:milatuzumab
keywords: Antibody-based immunotherapy; immunotherapy; lymphoid leukemia; lymphoma and Hodgkin disease