Gemtuzumab ozogamicin
Encyclopedia
Gemtuzumab ozogamicin is a drug-linked monoclonal antibody that was used to treat acute myelogenous leukemia from 2000-2010. It was withdrawn from market in June 2010 when a clinical trial showed the drug increased patient death and added no benefit over conventional cancer therapies.
Gemtuzumab is a monoclonal antibody to CD33
linked to a cytotoxic agent from the class of calicheamicin
s. CD33 is expressed in most leukemic blast cells but also in normal hematopoietic cells, the intensity diminishing with maturation of stem cells. In the United States, it was approved under an accelerated-approval process by the FDA in 2000 for use in patients over the age of 60 with relapsed acute myelogenous leukemia (AML); or those who are not considered candidates for standard chemotherapy.
Within the first year after approval, the FDA required a black box warning be added to Gemtuzumab packaging. The drug was noted to increase the risk of veno-occlusive disease in the absence of bone marrow transplantation. Later the onset of VOD was shown to occur at increased frequency in Gemtuzumab patients even following bone marrow transplantation. The drug was discussed in a 2008 JAMA article, which criticized the inadequacy of postmarketing surveillance of biologic agents.
Common side effects of administration included shivering, fever
, nausea
and vomiting.
Serious side effects included severe myelosuppression (suppressed activity of bone marrow
, which is involved in formation of various blood cell
s [found in 98% of patients]), disorder of the respiratory system
, tumor lysis syndrome
, Type III hypersensitivity, venous occlusion, and death.
In June 2010, Pfizer withdrew Mylotarg from the market at the request of the US FDA.
Gemtuzumab is a monoclonal antibody to CD33
CD33
CD33 or Siglec-3 is a transmembrane receptor expressed on cells of myeloid lineage. It is usually considered myeloid-specific, but it can also be found on some lymphoid cells.It binds sialic acids, therefore is a member of the SIGLEC family of lectins....
linked to a cytotoxic agent from the class of calicheamicin
Calicheamicin
The calicheamicins are a class of enediyne antibiotics derived from the bacterium Micromonospora echinospora, with calicheamicin γ1 being the most notable. It was isolated originally from a rock collected by a Scripps Research Institute chemist while hiking in Waco, Texas. It is extremely toxic to...
s. CD33 is expressed in most leukemic blast cells but also in normal hematopoietic cells, the intensity diminishing with maturation of stem cells. In the United States, it was approved under an accelerated-approval process by the FDA in 2000 for use in patients over the age of 60 with relapsed acute myelogenous leukemia (AML); or those who are not considered candidates for standard chemotherapy.
Within the first year after approval, the FDA required a black box warning be added to Gemtuzumab packaging. The drug was noted to increase the risk of veno-occlusive disease in the absence of bone marrow transplantation. Later the onset of VOD was shown to occur at increased frequency in Gemtuzumab patients even following bone marrow transplantation. The drug was discussed in a 2008 JAMA article, which criticized the inadequacy of postmarketing surveillance of biologic agents.
Common side effects of administration included shivering, fever
Fever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
, nausea
Nausea
Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...
and vomiting.
Serious side effects included severe myelosuppression (suppressed activity of bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
, which is involved in formation of various blood cell
Blood cell
A blood cell, also called a hematocyte, is a cell normally found in blood. In mammals, these fall into three general categories:* red blood cells — Erythrocytes* white blood cells — Leukocytes* platelets — Thrombocytes...
s [found in 98% of patients]), disorder of the respiratory system
Respiratory system
The respiratory system is the anatomical system of an organism that introduces respiratory gases to the interior and performs gas exchange. In humans and other mammals, the anatomical features of the respiratory system include airways, lungs, and the respiratory muscles...
, tumor lysis syndrome
Tumor lysis syndrome
In medicine , tumor lysis syndrome is a group of metabolic complications that can occur after treatment of cancer, usually lymphomas and leukemias, and sometimes even without treatment...
, Type III hypersensitivity, venous occlusion, and death.
Withdrawal from market
A randomized phase 3 comparative controlled trial (SWOG S0106) was initiated in 2004 by Wyeth in accordance with the FDA accelerated-approval process. The study was stopped prior to completion due to worrisome outcomes. Among the patients evaluated, fatal toxicity rate was significantly higher in the gemtuzumab combination therapy group vs the standard therapy group. Mortality was 5.7% with gemtuzumab and 1.4% without the agent (16/283 = 5.7% vs 4/281 = 1.4%; P = .01).In June 2010, Pfizer withdrew Mylotarg from the market at the request of the US FDA.