Mylotarg: antibody-targeted chemotherapy comes of age

  title={Mylotarg: antibody-targeted chemotherapy comes of age},
  author={Eric L. Sievers and Michael L. Linenberger},
  journal={Current Opinion in Oncology},
Mylotarg (gemtuzumab ozogamicin, CMA-676; Wyeth-Ayerst Laboratories, Philadelphia, PA) recently was approved by the US Food and Drug Administration for the treatment of patients with CD33-positive acute myeloid leukemia in first relapse, age 60 years or older, who are not considered candidates for other types of cytotoxic chemotherapy. In combined phase II studies of 142 patients with CD33-positive acute myeloid leukemia in first relapse, Mylotarg monotherapy was associated with a 30% overall… 

Gemtuzumab Ozogamicin (CMA-676, Mylotarg) for the treatment of CD33+ acute myeloid leukemia.

Future phase III trials will show the most suitable place of GO in the treatment of AML, with the most frequent adverse effect observed is myelotoxicity, with prolonged neutropenia and thrombocytopenia.

Immunobiologic therapies for myelodysplastic syndrome.

  • F. Appelbaum
  • Biology, Medicine
    Best practice & research. Clinical haematology
  • 2004

Gemtuzumab Ozogamicin

Gemtuzumab ozogamicin is a valuable new treatment option for patients aged ≥60 years with CD33-positive AML in first relapse for whom other cytotoxic chemotherapy is not considered appropriate; patients with a first CR (CR1) of >12 months are likely to have the best outcome.

Gemtuzumab Ozogamicin (Mylotarg®) in Children with Refractory or Relapsed Acute Myeloid Leukemia

Gemtuzumab ozogamicin therapy can induce blast reduction in children who have no further conventional treatment options and seems to be feasible for children with a sufficient general condition.

Gemtuzumab ozogamicin: first clinical experiences in children with relapsed/refractory acute myeloid leukemia treated on compassionate-use basis.

Clinical efficacy of GO is demonstrated in a subset of relapsed/refractory pediatric CD33(+) AML patients and suggests that intensive postremission therapy after remission induction by GO may result in durable responses in some patients, although follow-up is still short.

Target Therapy in Hematological Malignancies

The most recent 15 years has encountered a rapidly broadening interest and acknowledg-ment that leukemic stem cells, including an enhanced capacity to target them, may hold the way to enhanced reaction and diminished relapse rates over both lymphoid and myeloid disorders.

Efficient Elimination of B-Lineage Lymphomas by Anti-CD20–Auristatin Conjugates

Data indicate that anti-CD20–based antibody-drug conjugates are effective antitumor agents when prepared with a stable, enzyme-cleavable peptide linkage to highly potent cytotoxic agents such as MMAE.

Differential response of human acute myeloid leukemia cells to gemtuzumab ozogamicin in vitro: role of Chk1 and Chk2 phosphorylation and caspase 3.

Investigation of the effects of GO on human myeloid leukemia lines of different French-American-British (FAB) types suggests that the different molecular pathways induced by the drug in vitro may reflect the variable response to GO obtained in vivo.

Targeted therapy for hematologic malignancies.

  • P. Kuriakose
  • Medicine, Biology
    Cancer control : journal of the Moffitt Cancer Center
  • 2005
Targeted therapy of hematologic malignancies seems to be an effective and less toxic approach to the treatment of such disorders.



Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse.

  • E. SieversR. Larson F. Appelbaum
  • Medicine, Biology
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2001
Administration of the antibody-targeted chemotherapy agent Mylotarg to patients with CD33-positive acute myeloid leukemia in first relapse induces complete remissions with what appears to be a favorable safety profile.

Supersaturating infusional humanized anti-CD33 monoclonal antibody HuM195 in myelogenous leukemia.

These studies suggest that high doses of HuM195 achieve a long serum half-life, with tolerable toxicity and without immunogenicity, and one patient with acute myelogenous leukemia achieved a complete remission, lasting > 32 months, at the first dose level.

Targeting of the CD33-calicheamicin immunoconjugate Mylotarg (CMA-676) in acute myeloid leukemia: in vivo and in vitro saturation and internalization by leukemic and normal myeloid cells.

Data indicate that Mylotarg is rapidly and specifically targeted to CD33(+) cells, followed by internalization and subsequent induction of cell death, which is a promising therapy in patients with acute myeloid leukemia.

Multidrug-resistance phenotype and clinical responses to gemtuzumab ozogamicin.

Expression of multidrug resistance (MDR) features by acute myeloid leukemia (AML) cells predicts a poor response to many treatments. The MDR phenotype often correlates with expression of

Calicheamicin-conjugated humanized anti-CD33 monoclonal antibody (gemtuzumab zogamicin, CMA-676) shows cytocidal effect on CD33-positive leukemia cell lines, but is inactive on P-glycoprotein-expressing sublines

A dose-dependent, selective cytotoxic effect of CMA-676 was observed in cell lines that expressed CD33, and was dependent on the amount of CD33 and the proliferative speed of the cells.

Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model.

A nude mouse xenograft model using the human acute leukemia cell line, HEL, is developed and results indicate that this model system will be useful in evaluating the interaction of radiolabeled antibodies with human acute myeloid leukemia cells in an in vivo setting.

Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression.

  • T. DavisD. CzerwinskiR. Levy
  • Medicine, Biology
    Clinical cancer research : an official journal of the American Association for Cancer Research
  • 1999
This is the first identified case of loss of CD20 expression in a lymphoma that has relapsed after rituximab therapy, although several other cases have since been identified.

A stratification system for evaluating and selecting therapies in patients with relapsed or primary refractory acute myelogenous leukemia.

A system that stratifies patients by probability of response to previous salvage agents and may be useful when comparing new salvage regimens and when considering which patients might be candidates for phase I studies is developed.


The feasibility of using a radiolabeled antimyeloid antibody as part of a marrow transplant preparative regimen is demonstrated and a major limitation of using conventionally labeled anti-CD33 is highlighted—namely, the short residence time in marrow.