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 M 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

Research output: Contribution to journalArticle

216 Citations (Scopus)

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
Externally publishedYes

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Immunoconjugates
Maximum Tolerated Dose
B-Cell Lymphoma
Non-Hodgkin's Lymphoma
Pharmacokinetics
Safety
Follicular Lymphoma
Lymphoma, Large B-Cell, Diffuse
Thrombocytopenia
Therapeutics
Disease-Free Survival
Antibodies, Monoclonal, Humanized
Asthenia
Cytotoxins
Inotuzumab Ozogamicin
Neutropenia
Nausea
Anti-Idiotypic Antibodies
Drug Therapy
Survival

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

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. / Advani, Anjali; Coiffier, Bertrand; Czuczman, Myron S.; Dreyling, Martin; Foran, James M; Gine, Eva; Gisselbrecht, Christian; Ketterer, Nicolas; Nasta, Sunita; Rohatiner, Ama; Schmidt-Wolf, Ingo G H; Schuler, Martin; Sierra, Jorge; Smith, Mitchell R.; Verhoef, Gregor; Winter, Jane N.; Boni, Joseph; Vandendries, Erik; Shapiro, Mark; Fayad, Luis.

In: Journal of Clinical Oncology, Vol. 28, No. 12, 20.04.2010, p. 2085-2093.

Research output: Contribution to journalArticle

Advani, A, Coiffier, B, Czuczman, MS, Dreyling, M, Foran, JM, Gine, E, Gisselbrecht, C, Ketterer, N, Nasta, S, Rohatiner, A, Schmidt-Wolf, IGH, Schuler, M, Sierra, J, Smith, MR, Verhoef, G, Winter, JN, 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, vol. 28, no. 12, pp. 2085-2093. https://doi.org/10.1200/JCO.2009.25.1900
Advani, Anjali ; Coiffier, Bertrand ; Czuczman, Myron S. ; Dreyling, Martin ; Foran, James M ; Gine, Eva ; Gisselbrecht, Christian ; Ketterer, Nicolas ; Nasta, Sunita ; Rohatiner, Ama ; Schmidt-Wolf, Ingo G H ; Schuler, Martin ; Sierra, Jorge ; Smith, Mitchell R. ; Verhoef, Gregor ; Winter, Jane N. ; Boni, Joseph ; Vandendries, Erik ; Shapiro, Mark ; Fayad, Luis. / 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. In: Journal of Clinical Oncology. 2010 ; Vol. 28, No. 12. pp. 2085-2093.
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AU - Schmidt-Wolf, Ingo G H

AU - Schuler, Martin

AU - Sierra, Jorge

AU - Smith, Mitchell R.

AU - Verhoef, Gregor

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AU - Vandendries, Erik

AU - Shapiro, Mark

AU - Fayad, Luis

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