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Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin)

Leukemia volume 16, pages 1627–1636 (2002)Cite this article

Abstract

We analyzed the safety and efficacy of Mylotarg (gemtuzumab ozogamicin, an antibody-targeted chemotherapy consisting of a humanized anti-CD33 antibody linked to calicheamicin, a potent antitumor antibiotic) in the treatment of 101 patients ≥60 years of age with acute myeloid leukemia (AML) in untreated first relapse in three open-label trials. Mylotarg is administered as a 2-h intravenous infusion at 9 mg/m2 for two doses with 14 days between doses. The overall remission rate was 28%, with complete remission (CR) in 13% of patients and complete remission with incomplete platelet recovery (CRp) in 15%. Median survival was 5.4 months for all patients and 14.5 months and 11.8 months for patients achieving CR and CRp, respectively. CD33 antigen is present on normal hematopoietic progenitor cells; thus, an expected high incidence of grade 3 or 4 neutropenia (99%) and thrombocytopenia (99%) was observed. The incidences of grade 3 or 4 elevations of bilirubin and hepatic transaminases were 24% and 15%, respectively. There was a low incidence of grade 3 or 4 mucositis (4%) and infections (27%) and no treatment-related cardiotoxicity, cerebellar toxicity, or alopecia. Mylotarg is an effective treatment for older patients with CD33-positive AML in first relapse and has acceptable toxicity.

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Acknowledgements

We thank Matthew Sherman for study guidance, Beth Ford, Chantal Lejeune, Laura Manley, Allegra Stone, and Joanne Vanak for study management, Vincent van der Velden for laboratory analysis, Lance Leopold for the literature review, Nadine Dodge for clinical programming, Robert Herbertson and Denise Sarkozy for biostatistical analysis, and Susan Leinbach for manuscript preparation. We also thank all the patients and clinical personnel who participated in these studies. This study was supported in part by research funding from Wyeth-Ayerst Research to RAL, MB, EE, CK, EAS, ELS, PM, JMB, MRL, JJMvD, IDB, and FRA.

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Authors and Affiliations

  1. Department of Medicine, University of Chicago, Chicago, IL, USA

    RA Larson

  2. Department of Hematology, Universitair Ziekenhuis Gasthuisberg, Leuven, Belgium

    M Boogaerts

  3. MD Anderson Cancer Center, Houston, TX, USA

    E Estey

  4. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    C Karanes

  5. Hematologic Malignancies Program, University of Pennsylvania Cancer Center, Philadelphia, PA, USA

    EA Stadtmauer

  6. Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA

    EL Sievers, ID Bernstein & FR Appelbaum

  7. Department of Pediatrics, University of Washington, Seattle, WA, USA

    EL Sievers & ID Bernstein

  8. Department of Hemato-Oncology, Hospital Saint Joseph, Gilly-Charlerloi, Belgium

    P Mineur

  9. University of Rochester Medical Center, Rochester, NY, USA

    JM Bennett

  10. Wyeth-Ayerst Research, Collegeville, PA, USA

    MS Berger, CB Eten & M Munteanu

  11. Hematologics Inc., Seattle, WA, USA

    MR Loken

  12. Department of Immunology, Erasmus University Medical Center Rotterdam, Rotterdam, The Netherlands

    JJM van Dongen

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Appendix

Appendix

Additional investigators in the Mylotarg Study Group are: H Dombret, Hospital Saint Louis, Paris, France; J-L Harousseau, Centre Hospitalier Régional, Nantes Cedex, France; M Schuster, New York Hospital, Cornell Medical Center, New York, NY; M Tallman, Northwestern School of Medicine, Chicago, IL; M Theobald, Johannes Gutenberg University, Mainz, Germany; S Castaigne, Hospital A Mignot, Le Chesday, France; G Ehninger, University Hospital Dresden, Dresden, Germany; M Gramatzki, University Hospital Erlangen-Nuremberg, Erlangen, Germany; A Granena, Hospital Duran I Reynals, Barcelona, Spain; P Huijgens, Academisch Ziekenhuis VU, Amsterdam, The Netherlands; G Juliusson, University of Linköping, Linköping, Sweden; B Löwenberg, University Hospital Rotterdam, Rotterdam, The Netherlands; D-C Roy, Hospital Maisonneuve-Rosemont, Montreal, Quebec, Canada; R Spielberger, City of Hope National Medical Center, Duarte, CA; L Stenke, Karolinska Hospital, Stockholm, Sweden; D Voliotis, University Hospital Cologne, Cologne, Germany; M Aglietta, Ospedasle Mauriziano Umberto, Torino, Italy; A Burnett, University of Wales, Cardiff, United Kingdom; N Cambier, University of Lille, Lille Cedex, France; P Cassileth, University of Miami, Miami, FL; DD Clausen, University Medical Center at Stony Brook, Stony Brook, NY; S Coutre, Stanford University Medical Center, Stanford, CA; H Erba, University of Michigan Medical Center, Ann Arbor, MI; J Esteve, Hospital Clinic I Provincial, Barcelona, Spain; M Gobbi, Universitá degli Studi di Genova, Genova, Italy; A Goldstone, University College Hospital, London, United Kingdom; G Heil, Medizinische Hoschule Hannover, Hannover, Germany; H-A Horst, Städt Krankenhaus, Kiel, Germany; A List, Arizona Cancer Center, Tucson, AZ; JD Mediavilla, Hospital Clinico San Carlos, Madrid, Spain; M Minden, Princess Margaret Hospital, Toronto, Ontario, Canada; F Nobile, Ospedali Riuniti di Reggio Calabria, Reggio Calabria, Italy; BABS Parreira, Institutio Portugues de Oncologia, Lisboa-Codex, Portugal; C Paul, Huddinge sjh, Huddinge, Sweden; K Rai, Long Island Jewish Medical Center, New Hyde Park, NY; D Schenkein, New England Medical Center, Boston, MA; G Schiller, UCLA Center for Health Science, Los Angeles, CA; B Simonsson, Akademiska Hospital, Uppsala, Sweden; S Tarantolo, University of Nebraska Medical Center, Omaha, NE.

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Larson, R., Boogaerts, M., Estey, E. et al. Antibody-targeted chemotherapy of older patients with acute myeloid leukemia in first relapse using Mylotarg (gemtuzumab ozogamicin). Leukemia 16, 1627–1636 (2002). https://doi.org/10.1038/sj.leu.2402677

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