Brand Name Drug: Mylotarg
Active Ingredient Drug: gemtuzumab ozogamicin
Indication: Treatment of patients aged 60 or older with CD33-positive relapsed acute myeloid leukemia
Company Name: American Home Products Corporation, Wyeth-Ayerst Laboratories division
Availability: Approved by FDA on May 18, 2000.
Acute myeloid leukemia (AML) is the most common type afflicting adults, with some 9,700 new cases predicted to be diagnosed in the US this year. Current treatment regimens center on non-specific combinations of chemotherapeutic drugs, as well as bone marrow transplants in some patients. Even with these treatments, about half of AML patients continue to harbor residual cancer cells or relapse, and only about 20% survive five years or more.
A new highly targeted drug developed by the Wyeth-Ayerst Laboratories division of American Home Products Corporation may help those AML patients age 60 and over who have relapsed following previous chemotherapeutic regimens: Mylotarg (gemtuzumab ozogamicin). The FDA’s Oncologic Drugs Advisory Committee recommended accelerated approval of Mylotarg for this patient group – which makes up 75% of AML patients – on March 17, 2000. Mylotarg consists of an anticancer drug attached to a monoclonal antibody that homes in on AML cells. If approved, American Home Products notes that Mylotarg would be the first chemotherapy agent targeted directly to cancerous cells using monoclonal antibody technology.
How It Works
Mylotarg (gemtuzumab ozogamicin) is a humanized recombinant monoclonal antibody linked to a potent antitumor antibiotic called calicheamicin, a substance isolated from a bacterium in caliche clay, a soil found in the desert southwest. The anticancer activity of calicheamicin is attributed to its ability to induce double-stranded DNA breaks. The antibody portion of Mylotarg is specific for the CD33 antigen, a glycoprotein commonly expressed by myeloid leukemia cells. The antibody zeroes in on AML cells and delivers calicheamicin directly to these cells, where it can exert its cytotoxic activity.
Because CD33 is absent from the surfaces of normal hematopoietic stem cells, these cells are spared from the toxic effects of calicheamicin, making Mylotarg more tolerable than conventional forms of chemotherapy used to treat AML.
Mylotarg (gemtuzumab ozogamicin): Clinical Study Results
In a phase I dose-escalation study, 40 patients with relapsed or refractory CD33(+) AML were treated with Mylotarg (referred to as CMA-676 in clinical studies). Leukemia was eliminated from the blood and marrow of 8 (20%) of the 40 patients; blood counts returned to normal in three (8%) patients. Mylotarg was generally well tolerated, with fever and chills being the most common side effects. Two patients who were treated at the highest dose level (9 mg/m2) were neutropenic more than 5 weeks after the last dose of Mylotarg.
Preliminary results of phase II clinical trials of Mylotarg (gemtuzumab ozogamicin) were presented at the 1999 annual meeting of the American Society of Clinical Oncology. A group of AML patients who had relapsed following initial chemotherapy treatment were given Mylotarg in two intravenous infusions 14 days apart. Remission was achieved by 36% of patients – a rate comparable to that of standard combination chemotherapy agents, but with far fewer side effects, due largely to the specific action of the drug.
A phase III study has been performed involving patients with AML in first relapse. An interim analysis of the first 23 patients found that in 10, treatment with Mylotarg resulted in elimination of blasts from peripheral blood and marrow.
What the Patient Should Know
Fever and chills following the infusion of Mylotarg (gemtuzumab ozogamicin) were the primary side effects associated with the drug. Some patients may develop neutropenia. This side effects profile is especially attractive for treating older patients, who are less likely to tolerate the organ damage, mouth sores, and gastrointestinal lesions associated with standard chemotherapy regimens. Patients may be also able to receive the drug on an outpatient basis.