Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence

Authors

  • Richard A. Larson M.D.,

    Corresponding author
    1. Department of Medicine, University of Chicago, Chicago, Illinois
    • Section of Hematology/Oncology, The University of Chicago, MC-21155841 S. Maryland Avenue, Chicago, IL 60637
    Search for more papers by this author
    • Fax: (773) 702-3002

  • Eric L. Sievers M.D.,

    1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    2. Department of Pediatrics, University of Washington, Seattle, Washington
    Search for more papers by this author
  • Edward A. Stadtmauer M.D.,

    1. Hematologic Malignancies Program, University of Pennsylvania Cancer Center, Philadelphia, Pennsylvania
    Search for more papers by this author
  • Bob Löwenberg M.D.,

    1. Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
  • Elihu H. Estey M.D.,

    1. Department of Leukemia, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    Search for more papers by this author
  • Hervé Dombret M.D.,

    1. Hospital Saint Louis, Paris, France
    Search for more papers by this author
  • Matthias Theobald M.D.,

    1. Department of Hematology, Johannes Gutenberg University, Mainz, Germany
    Search for more papers by this author
  • Dimitris Voliotis M.D.,

    1. Department of Oncology, University Hospital Cologne, Cologne, Germany
    Search for more papers by this author
  • John M. Bennett M.D.,

    1. University of Rochester Medical Center, Rochester, New York
    Search for more papers by this author
    • Dr. Bennett is a consultant for morphology review for Wyeth Pharmaceuticals.

  • Maria Richie B.S.,

    1. Wyeth Research, Collegeville, Pennsylvania
    Search for more papers by this author
    • Dr. Richie was employed by Wyeth Research during her participation in this project. She currently is employed by Glaxo SmithKline and has no financial interest in Wyeth.

  • Lance H. Leopold M.D.,

    1. Wyeth Research, Collegeville, Pennsylvania
    Search for more papers by this author
    • Dr. Leopold previously was employed by Wyeth Pharmaceuticals.

  • Mark S. Berger M.D.,

    1. Wyeth Research, Collegeville, Pennsylvania
    Search for more papers by this author
    • Dr. Berger previously was employed by Wyeth Pharmaceuticals and owns stock in Wyeth Pharmaceuticals.

  • Matthew L. Sherman M.D.,

    1. Wyeth Research, Collegeville, Pennsylvania
    Search for more papers by this author
    • Dr. Sherman previously was employed by Wyeth Pharmaceuticals.

  • Michael R. Loken Ph.D.,

    1. Hematologics Inc., Seattle, Washington
    Search for more papers by this author
  • Jacques J. M. van Dongen M.D., Ph.D.,

    1. Department of Immunology, Erasmus University Medical Center, Rotterdam, The Netherlands
    Search for more papers by this author
    • Dr. van Dongen has received payment for laboratory diagnostics for the European patients on the CD33 treatment protocol.

  • Irwin D. Bernstein M.D.,

    1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    2. Department of Pediatrics, University of Washington, Seattle, Washington
    Search for more papers by this author
    • Dr. Bernstein is employed by the Fred Hutchinson Cancer Research Center, which is the owner of the anti-CD33 antibody used in the development of gemtuzumab ozogamicin (Mylotarg), an agent used to treat patients with acute myeloid leukemia (AML). Under the Fred Hutchinson Cancer Research Center's Patents and Inventions Policy, as an inventor of the antibody, Dr. Bernstein is entitled to a share of any royalties that the Fred Hutchinson Cancer Research Center received from Wyeth-Ayerst Research under the Exclusive License Agreement dated December 1, 1994, between American Cyanamid (now Wyeth-Ayerst) and the Fred Hutchinson Cancer Research Center.

  • Frederick R. Appelbaum M.D.,

    1. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington
    Search for more papers by this author
  • Mylotarg Study Group

    Search for more papers by this author
    • Additional investigators in the Mylotarg Study Group are M. Boogaerts, Universitair Ziekenhuis Gasthuisberg, Leuven Belgium; S. Castaigne, Hôpital A. Mignot, Le Chesday, France; P. Huijgens, Academisch Ziekenhuis VU, Amsterdam, The Netherlands; R. Spielberger, City of Hope National Medical Center, Duarte, CA; M. Tallman, Northwestern University Feinberg School of Medicine, Chicago, IL; C. Bernasconi. Istituto di Ematolgia, Policlinico S. Matteo, Pavia, Italy; J.-L. Harousseau, C.H.U. Nantes-Hotel Dieu, Nantes, France; C. Karanes, Karmanos Cancer Institute, Wayne State University, Detroit, MI; A. List, Arizona Cancer Center, Tucson, AZ; D.-C. Roy, Hôpital Maisonneuve-Rosemont, Montreal, Quebec, Canada; A. Goldstone, University College Hospital, London, United Kingdom; F. Mandelli, Azienda Policlinico Universitario, Roma, Italy; M. Schuster, Weill Medical College of Cornell University, New York, NY; M. Gobbi, Universitá degli Studi di Genova, Genova, Italy; P. Mineur, Hôpital St. Joseph, Charlerloi, Belgium; S. Tarantolo, University of Nebraska Medical Center, Omaha, NE; M. Andre, Clinique Notre-Dame-Reine Fabiola, Charleroi, Belgium; A. Burnett, University of Wales, Cardiff, United Kingdom; N. Cambier, Centre Hospitalier Regional et Universitair de Lille, Lille, France; P. Cassileth, University of Miami, Miami, FL; J. Esteve, Hospital Clinic, Barcelona, Spain; M. Gramatzki, University Hospital Erlangen-Nuremberg, Erlangen, Germany; G. Heil, Medizinische Hoschule Hannover, Hannover, Germany; G. Juliusson, University of Linköping, Linköping, Sweden; S. Tura, Istituto di Ematologia e Oncologia, Policlinico S. Orsola-Malpighi, Bologna, Italy; G. Ehninger, University Hospital Dresden, Dresden, Germany; G. A. Granena, Hospital Duran I Reynals, Barcelona, Spain; J. Karp, University of Maryland, Baltimore, MD; J.-P. Marie, Hotel Dieu, Paris, France; A. Parreira, Institutio Português de Oncologia, Lisboa, Portugal; C. Paul, Hematologkliniken, Huddinge, Huddinge, Sweden; K. Rai, Long Island Jewish Medical Center, New Hyde Park, NY; G. Schiller, University of California-Los Angeles Center for Health Science, Los Angeles, CA; J. Sierra; Hospital de la Santa Creu I San Pau, Barcelona, Spain; B. Simonsson, Akademiska Hospital, Uppsala, Sweden; L. Stenke, Karolinska Hospital, Danderyd, Sweden; M. Wernli, Cantonal Hospital, Aarau, Switzerland; R. Willemze, Leiden University Medical Center, Leiden, The Netherlands; M. Aglietta, Ospedale Mauriziano Umberto, Torino, Italy; D. Clausen, University Medical Center at Stony Brook, Stony Brook, NY; J. Conde, Hospital Clinico Universitario de Valencia, Valencia, Spain; S. Coutre, Stanford University Medical Center, Stanford, CA; M.-N. Fernãndez, Hospital Puerta de Hierro, Madrid, Spain; D. Fiere, Hospital Edouard Herriot, Lyon, France; U. Hess, Cantonal Hospital, St. Gallen, Switzerland; H.-A. Horst, University Hospital, Kiel, Germany; W. Linkesch, University Hospital, Graz, Austria; D. Mediavilla, Hospital Clinico San Carlos, Madrid, Spain; M. Minden, Princess Margaret Hospital, Toronto, Ontario, Canada; F. Nobile, Ospedali Riuniti di Reggio Calabria, Calabria, Italy; D. Schenkein, New England Medical Center, Boston, MA; A. Wahlin, Norrlands University Hospital, Umea, Sweden.


Abstract

BACKGROUND

In this study, the authors analyzed the efficacy and safety of gemtuzumab ozogamicin (GO) (Mylotarg®), an antibody-targeted chemotherapy for CD33-positive acute myeloid leukemia (AML).

METHODS

Patients with CD33-positive AML in first recurrence were entered in 3 open-label, single-arm, Phase II studies. Patients received monotherapy with GO 9 mg/m2 as a 2-hour intravenous infusion in 2 doses separated by 2 weeks. Patients were evaluated for remission, survival, and treatment-emergent adverse events.

RESULTS

Two hundred seventy-seven patients (median age, 61 yrs) were treated with GO, and 71 patients (26%) achieved remission, which was defined as ≤ 5% blasts in the bone marrow without leukemic blasts in the peripheral blood, neutrophil recovery to ≥ 1500/μL, hemoglobin ≥ 9 g/dL, and independence from red blood cell and platelet transfusions. Complete remission (CR) with platelet recovery (≥ 100,000/μL) or without full platelet recovery (< 100,000/μL) (CRp) was observed in 35 patients (13%) and 36 patients (13%), respectively. The median recurrence-free survival was 6.4 months for patients who achieved CR and 4.5 months for patients who achieved CRp. Although expected incidences of Grade 3 or 4 neutropenia (98%) and thrombocytopenia (99%) were observed, the incidence of Grade 3 or 4 sepsis (17%) and pneumonia (8%) was relatively low. Grade 3 or 4 hyperbilirubinemia and hepatic aspartate aminotransferase and alanine aminotransferase elevations were reported in 29%, 18%, and 9% of patients, respectively; 0.9% of patients who did not undergo prior or subsequent hematopoietic stem cell transplantation developed hepatic venoocclusive disease after GO treatment.

CONCLUSIONS

When it was administered to patients with CD33-positive AML in first recurrence, single-agent GO induced a 26% remission rate with a generally acceptable safety profile. Cancer 2005. © 2005 American Cancer Society.

Ancillary