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

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

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232 Scopus citations

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/m2. 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/m2. 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.

Original languageEnglish (US)
Pages (from-to)2085-2093
Number of pages9
JournalJournal of Clinical Oncology
Volume28
Issue number12
DOIs
StatePublished - Apr 20 2010

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Advani, A., Coiffier, B., Czuczman, M. S., Dreyling, M., Foran, J., Gine, E., Gisselbrecht, C., Ketterer, N., Nasta, S., Rohatiner, A., Schmidt-Wolf, I. G. H., Schuler, M., Sierra, J., Smith, M. R., Verhoef, G., Winter, J. N., Boni, J., Vandendries, E., Shapiro, M., & Fayad, L. (2010). 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. Journal of Clinical Oncology, 28(12), 2085-2093. https://doi.org/10.1200/JCO.2009.25.1900