title: The combination of milatuzumab, a humanized anti-CD74 antibody, and veltuzumab, a humanized anti-CD20 antibody, demonstrates activity in patients with relapsed and refractory B-cell non-Hodgkin lymphoma.
abstract: As a result of the anti-tumour activity observed in vitro and in vivo with combined anti-CD20 and anti-CD74 antibodies, we initiated a phase I/II trial of veltuzumab and milatuzumab in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (NHL). Patients received an induction of veltuzumab 200 mg/m(2) weekly combined with escalating doses of milatuzumab at 8, 16 and 20 mg/kg weekly for 4 weeks. Patients without disease progression could receive an extended induction with treatment on weeks 12, 20, 28 and 36. A total of 35 patients enrolled on the study. Median age was 63 years, median number of prior therapies was 3, and 63% of patients were rituximab refractory. No dose-limiting toxicities were observed in the phase I study. Related grade 3-4 toxicities included lymphopenia, leucopenia, neutropenia, anaemia, infusion reactions, hyperglycaemia, fatigue and atrial tachycardia. Median weeks of therapy was 12 and 29% of patients completed all 36 weeks of therapy. The overall response rate was 24%, median duration of response was 12 months, and responses were observed at all dose levels and in 50% of patients refractory to rituximab. Combination therapy with veltuzumab and milatuzumab demonstrated activity in a population of heavily pre-treated patients with relapsed or refractory indolent NHL.
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Beth A
authors.initials: BA
authors.lastname: Christian
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: Ming
authors.initials: M
authors.lastname: Poi
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Jones
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Porcu
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Kami
authors.initials: K
authors.lastname: Maddocks
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Flynn
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Don M
authors.initials: DM
authors.lastname: Benson
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.|College of Pharmacy, The Ohio State University, Columbus, OH, USA.
authors.forename: Mitch A
authors.initials: MA
authors.lastname: Phelps
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Lai
authors.initials: L
authors.lastname: Wei
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: John C
authors.initials: JC
authors.lastname: Byrd
authors.affiliation: Clinical Research, Immunomedics, Inc., Morris Plains, NJ, USA.
authors.forename: William A
authors.initials: WA
authors.lastname: Wegener
authors.affiliation: Clinical Research, Immunomedics, Inc., Morris Plains, NJ, USA.|Center for Molecular Medicine and Immunology, Garden State Cancer Center, Morris Plains, NJ, USA.
authors.forename: David M
authors.initials: DM
authors.lastname: Goldenberg
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Baiocchi
authors.affiliation: Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA.
authors.forename: Kristie A
authors.initials: KA
authors.lastname: Blum
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000493:pharmacokinetics; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000473:pathology*; D005260:Female; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C540932:milatuzumab; C493846:veltuzumab
keywords: extended dosing; milatuzumab; monoclonal antibody; non-Hodgkin lymphoma; veltuzumab
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