Safety, pharmacokinetics, and preliminary clinical activity of inotuzumab ozogamicin, a novel immunoconjugate for the treatment of B-cell non-Hodgkin's lymphoma: results of a phase I study.

Abstract

PURPOSE Inotuzumab ozogamicin (CMC-544) is an antibody-targeted chemotherapy agent composed of a humanized anti-CD22 antibody conjugated to calicheamicin, a potent cytotoxic agent. This was a phase I study to determine the maximum-tolerated dose (MTD), safety, and preliminary efficacy of inotuzumab ozogamicin in an expanded MTD cohort of patients with relapsed or refractory CD22(+) B-cell non-Hodgkin's lymphoma (NHL). PATIENTS AND METHODS Inotuzumab ozogamicin was administered intravenously as a single agent once every 3 or 4 weeks at doses ranging from 0.4 to 2.4 mg/m(2). Outcomes included MTD, safety, pharmacokinetics, response, progression-free survival (PFS), and overall survival. Results Seventy-nine patients were enrolled. The MTD was determined to be 1.8 mg/m(2). Common adverse events at the MTD were thrombocytopenia (90%), asthenia (67%), and nausea and neutropenia (51% each). The objective response rate at the end of treatment was 39% for the 79 enrolled patients, 68% for all patients with follicular NHL treated at the MTD, and 15% for all patients with diffuse large B-cell lymphoma treated at the MTD. Median PFS was 317 days (approximately 10.4 months) and 49 days for patients with follicular NHL and diffuse large B-cell lymphoma, respectively. CONCLUSION Inotuzumab ozogamicin has demonstrated efficacy against CD22(+) B-cell NHL, with reversible thrombocytopenia as the main toxicity.

• Authors: Anjali Advani, Bertrand Coiffier, Myron S Czuczman, Martin Dreyling, James Foran, Eva Gine, Christian Gisselbrecht, Nicolas Ketterer, Sunita Nasta, Ama Rohatiner, Ingo G H Schmidt-Wolf, Martin Schuler, Jorge Sierra, Mitchell R Smith, Gregor Verhoef, Jane N Winter, Joseph Boni, Erik Vandendries, Mark Shapiro, Luis Fayad
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 28 Issue 12 Pg. 2085-93 (Apr 20 2010) ISSN: 1527-7755 [Electronic] United States
• PMID: 20308665 (Publication Type: Clinical Trial, Phase I, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents
• CD22 protein, human
• Immunotoxins
• Sialic Acid Binding Ig-like Lectin 2
• Inotuzumab Ozogamicin

Topics

• Adult
• Aged
• Aged, 80 and over
• Antibodies, Monoclonal (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Agents (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Disease-Free Survival
• Europe
• Female
• Humans
• Immunotoxins (administration & dosage, adverse effects, pharmacokinetics, therapeutic use)
• Infusions, Intravenous
• Inotuzumab Ozogamicin
• Kaplan-Meier Estimate
• Lymphoma, Follicular (drug therapy, immunology, mortality)
• Lymphoma, Large B-Cell, Diffuse (drug therapy, immunology, mortality)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Pilot Projects
• Sialic Acid Binding Ig-like Lectin 2 (immunology)
• Time Factors
• Treatment Outcome