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Incidence of sinusoidal obstruction syndrome following Mylotarg (gemtuzumab ozogamicin): a prospective observational study of 482 patients in routine clinical practice

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Abstract

The purpose of this prospective observational study was to determine the incidence of hepatic sinusoidal obstruction syndrome (SOS), following gemtuzumab ozogamicin (GO) therapy in routine clinical practice. Patients receiving GO for acute myeloid leukemia (AML) were eligible. Assessments were requested to be performed weekly for 6 weeks after the start of GO therapy or 4 weeks after the last dose (whichever was later), and after 6 months. The primary outcome variable was the incidence of SOS as judged by a panel of independent experts. A total of 512 patients were enrolled at 54 US centers and 482 were evaluable. The incidence of SOS in this study population was 9.1 % (44/482; 95 % confidence interval 6.9–12.0 %). Of the 44 patients classified as having SOS, 8 were mild, 17 moderate, and 19 severe; 33 died within 6 months (20 of disease progression and 13 of SOS and multiorgan failure). Most (68 %) patients in the study died within 6 months; most of these deaths (73 %) were due to progression of AML. Serious adverse events occurred in 85 % of patients, most (81 %) due to AML, febrile neutropenia, pyrexia, and sepsis. GO administered in routine clinical practice carries an overall 9.1 % risk of SOS and a 2.7 % risk of death from SOS and multiorgan failure. No risk factors were identified for the development of SOS.

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Acknowledgments

This study was sponsored by Wyeth Pharmaceuticals. Medical writing support was provided by Marcia Skoglund, PhD, at Healthcare Consulting and was funded by Wyeth. Wyeth was acquired by Pfizer Inc. in October 2009. This research was supported by Wyeth Pharmaceuticals.

Author information

Authors and Affiliations

  1. Memorial Sloan Kettering Cancer Center, Weill Cornell Medical College, 1275 York Ave., Box 381, New York, NY, 10065, USA

    Martin S. Tallman

  2. Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, WA, USA

    George B. McDonald

  3. Division of Gastrointestinal and Liver Diseases, University of Southern California Keck School of Medicine, Los Angeles, CA, USA

    Laurie D. DeLeve

  4. Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA

    Maria R. Baer

  5. Pfizer, Collegeville, PA, USA

    Michael N. Cook, G. Jay Graepel & Carl Kollmer

Authors
  1. Martin S. Tallman
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  2. George B. McDonald
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  3. Laurie D. DeLeve
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  4. Maria R. Baer
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  5. Michael N. Cook
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  6. G. Jay Graepel
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  7. Carl Kollmer
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Corresponding author

Correspondence to Martin S. Tallman.

Additional information

For the Mylotarg Study Group.

List of physicians that were part of the Mylotarg Study Group are given in the Appendix.

Appendix

Appendix

The following physicians were part of the Mylotarg Study Group:

David A. Rizzieri—Duke University Medical Center, Durham, NC.

Bayard Powell—Wake Forest University School of Medicine, Winston-Salem, NC.

David F. Claxton—Penn State Cancer Institute, Penn State College of Medicine, Hershey, PA.

Harry Erba—University of Michigan, Ann Arbor, MI.

Richard Larson—University of Chicago, Chicago, IL.

Harold Chung—Bone Marrow Transplant Unit MCV, Richmond, VA.

Ronald Sobecks—Cleveland Clinic Foundation-Hematology and Medical Oncology Cleveland, OH.

Maureen Cooper—Hematology Consultants, Indianapolis, IN.

Gary Schiller—UCLA, Los Angeles, CA.

Delong Liu—New York Medical College, Dept. of Oncology/Hematology, Valhalla, NY.

John D. Swanson—Fox Valley Hematology/Oncology, Appleton, WI.

Gwen Nichols—Div. Of Hem/Onc.650 W. 168 St. Suite BB20, New York, NY 10032.

Solveig Ericson—University of West Virginia Mary Babb Randolph Cancer Center, Morgantown, WV.

Lee Schwartzberg—West Cancer Clinic, Memphis, TN.

Madan Jagasia—The Vanderbilt Clinic, Vanderbilt University, Nashville, TN.

Thomas Martin—University of California at San Francisco, San Francisco, CA.

Raymond Hohl—University of Iowa Hospitals and Clinics, Iowa City, IA.

Frank Beardell—4735 Ogletown-Stanton Rd., Newark, DE.

Gloria Mattiuzzi—MD Anderson Cancer Center, Houston, TX.

Kanti Rai—Long Island Jewish Medical Center, New Hyde Park, NY.

Richard T. Maziarz-Oregon Health Services University, Portland, OR.

John Lister—Western Pennsylvania Hospital Cancer Institute, Pittsburg, PA.

Ronald Hoffman—University of Illinois at Chicago, Chicago IL.

Dianna Howard-University of Kentucky Markey Cancer Center, Lexington, KY.

Geoffrey Herzig—University of Louisville Brown Cancer Center, Louisville, KY.

Michael Lilly—Loma Linda University Cancer Institute, Loma Linda, CA.

Parameswaran Venugopal—Rush Cancer Institute, Chicago, IL.

Bipinkumar Amin—Clinical Research Center, St. Alexius/Prime Care Medical Arts Plaza, Bismarck, ND.

Romeo Mandanas—Cancer Care Association, Oklahoma City, OK.

Alan Campbell—Spectrum Health—Cook Research Dept., Grand Rapids, MI.

Andrew Haas—Akron General Medical Center, Akron, OH.

Glenn Mills, Feist-Weiller Cancer Center, Shrevport, LA.

Mike Perry—Ellis Fischel, Columbia, MD.

Leland Powell—Division of Hematology, Depart. Medicine, UCLA Medical Center, Sylmar, CA.

Jeffery Letzer—Kalamazoo Hematology/Oncology, Kalamazoo, MI.

Mark Brunvand—Rock Mountain Cancer Center, Denver, CO.

Mark Holguin—Scott White Clinic, Temple TX.

Prashant Patel—Martin Memorial Cancer Center, Stuart, FL.

Leonard White—Arch Medical Group, LLC, St Louis, MO.

R. Seth Cooper—St. Thomas Research Institute, Nashville, TN.

Edward Stadtmauer—University of Pennsylvania, Philadelphia, PA.

Kenneth Nahum—Jersey Shore University Medical Center, Neptune, NJ.

Luis Isola—Mt. Sinai Hospital, New York, NY.

Raymond Load—West Michigan Cancer Center and Institution for Blood Disorders, Kalamazoo, MI.

Neal Flomenberg—Thomas Jefferson University Blood Marrow Transplant, Philadelphia, PA.

Peter Wiernik—Our Lady of Mercy Cancer Center, Bronx, NY.

Richard Guidice—New Mexico Oncology Hematology Consultants, Albuquerque, NM.

Joseph Eid, New Brunswick, NJ.

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Tallman, M.S., McDonald, G.B., DeLeve, L.D. et al. Incidence of sinusoidal obstruction syndrome following Mylotarg (gemtuzumab ozogamicin): a prospective observational study of 482 patients in routine clinical practice. Int J Hematol 97, 456–464 (2013). https://doi.org/10.1007/s12185-013-1275-2

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  • DOI: https://doi.org/10.1007/s12185-013-1275-2

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