Mylotarg: antibody-targeted chemotherapy comes of age

@article{Sievers2001MylotargAC,
  title={Mylotarg: antibody-targeted chemotherapy comes of age},
  author={E. Sievers and M. Linenberger},
  journal={Current Opinion in Oncology},
  year={2001},
  volume={13},
  pages={522-527}
}
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… Expand
Gemtuzumab Ozogamicin (CMA-676, Mylotarg) for the treatment of CD33+ acute myeloid leukemia.
TLDR
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. Expand
Immunobiologic therapies for myelodysplastic syndrome.
  • F. Appelbaum
  • Medicine
  • Best practice & research. Clinical haematology
  • 2004
TLDR
The clearest example of successful immunotherapy for MDS (and AML) is the use of the graft-versus-tumor effect associated with allogeneic hematopoietic cell transplantation. Expand
Gemtuzumab Ozogamicin
TLDR
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. Expand
Gemtuzumab Ozogamicin (Mylotarg®) in Children with Refractory or Relapsed Acute Myeloid Leukemia
TLDR
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. Expand
Gemtuzumab ozogamicin: first clinical experiences in children with relapsed/refractory acute myeloid leukemia treated on compassionate-use basis.
TLDR
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. Expand
Target Therapy in Hematological Malignancies
TLDR
The most recent 15 years has encountered a rapidly broadening interest and acknowledgment 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. Expand
Efficient Elimination of B-Lineage Lymphomas by Anti-CD20–Auristatin Conjugates
TLDR
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. Expand
Differential response of human acute myeloid leukemia cells to gemtuzumab ozogamicin in vitro: role of Chk1 and Chk2 phosphorylation and caspase 3.
TLDR
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. Expand
Targeted therapy for hematologic malignancies.
  • P. Kuriakose
  • Medicine
  • Cancer control : journal of the Moffitt Cancer Center
  • 2005
TLDR
Targeted therapy of hematologic malignancies seems to be an effective and less toxic approach to the treatment of such disorders. Expand
Mechanism of action and resistance to monoclonal antibody therapy.
TLDR
Induction of apoptosis, antibody-dependent cell cytotoxicity, and complement-mediated cell death (CDC) is the proposed mechanism of action of these antibodies. Expand
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 29 REFERENCES
Efficacy and safety of gemtuzumab ozogamicin in patients with CD33-positive acute myeloid leukemia in first relapse.
TLDR
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. Expand
Supersaturating infusional humanized anti-CD33 monoclonal antibody HuM195 in myelogenous leukemia.
TLDR
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. Expand
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.
TLDR
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. Expand
A phase III comparison of high dose ARA-C (HIDAC) versus HIDAC plus mitoxantrone in the treatment of first relapsed or refractory acute myeloid leukemia Southwest Oncology Group Study.
TLDR
In this randomized trial, the addition of mitoxantrone to high-dose cytarabine was associated with a trend toward a higher CR rate and there was less evidence for an advantage in disease-free or overall survival, although any such conclusion is limited by the size of the study. Expand
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 ofExpand
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
TLDR
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. Expand
Localization of radiolabeled antimyeloid antibodies in a human acute leukemia xenograft tumor model.
TLDR
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. Expand
Therapy of B-cell lymphoma with anti-CD20 antibodies can result in the loss of CD20 antigen expression.
TLDR
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. Expand
A stratification system for evaluating and selecting therapies in patients with relapsed or primary refractory acute myelogenous leukemia.
TLDR
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. Expand
THE USE OF RADIOLABELED ANTI‐CD33 ANTIBODY TO AUGMENT MARROW IRRADIATION PRIOR TO MARROW TRANSPLANTATION FOR ACUTE MYELOGENOUS LEUKEMIA
TLDR
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. Expand
...
1
2
3
...