FDA Approval: Gemtuzumab ozogamicin (Mylotarg) for Leukemia

A drug that was approved, withdrawn, and came back

Most cancer drug histories run in one direction. Gemtuzumab ozogamicin, sold as Mylotarg, did not.

The FDA's own record of withdrawn accelerated approvals lists it. The original approval, dated May 17, 2000, covered patients with CD33-positive acute myeloid leukemia in first relapse who were 60 years of age or older and not candidates for cytotoxic chemotherapy. The withdrawal date recorded on that same FDA page is November 28, 2011.

The drug is on the market today, and its label carries an Initial U.S. Approval date of 2000. What changed was the dose schedule and the evidence behind it, not the molecule.

That history is the most useful thing about this approval. It is a worked example of what accelerated approval is for, and what happens when the confirmatory evidence does not hold up.

What the drug is

The label calls it a CD33-directed antibody and cytotoxic drug conjugate. That construction is worth unpacking.

An antibody-drug conjugate is two things joined together. One part is a monoclonal antibody, a lab-made protein that finds a specific target. Here the target is CD33, a protein carried on the surface of AML cells in most patients. The other part is a cell-killing chemotherapy payload attached to that antibody.

The idea is delivery. The antibody carries the toxin to cells that display CD33, rather than releasing it everywhere. Our page on targeted therapy covers the wider family of drugs built on this logic.

What the current label covers

Two indications:

• Newly diagnosed CD33-positive AML, in adults and in children aged 1 month and older.
• Relapsed or refractory CD33-positive AML, in adults and in children aged 2 years and older. Refractory means the disease did not respond to treatment.

Dosing is fractionated, meaning split into smaller doses rather than given all at once. For newly diagnosed AML in adults, induction is given on days 1, 4, and 7 alongside daunorubicin and cytarabine, at an amount worked out from body size and capped at a single vial. Consolidation is a single day-1 infusion, again with daunorubicin and cytarabine.

The fractionated schedule is the practical difference between the drug that was withdrawn and the drug in use now.

The warning that dominates monitoring

The label carries a boxed warning for hepatotoxicity, meaning liver injury. It names hepatic veno-occlusive disease, or VOD, also called sinusoidal obstruction syndrome, or SOS, and states that severe or fatal cases have been reported with this drug.

VOD happens when the small veins draining the liver become blocked. The liver swells, fluid builds up, and the organ can fail. It is a recognized complication of some intensive leukemia treatments and of stem cell transplant.

The signs to report immediately are rapid weight gain, swelling of the abdomen, pain in the upper right side of the abdomen, and yellowing of the skin or the whites of the eyes. Liver blood tests are monitored throughout treatment.

When to get checked

AML develops quickly. NCI names fever, feeling tired, and easy bruising or bleeding as the signs of AML. Smoking, previous chemotherapy, and radiation exposure raise risk.

For someone with a known or suspected leukemia, call the care team the same day for:

• Fever of 100.4 degrees Fahrenheit, or 38 degrees Celsius, or higher.
• Shaking chills.
• Bleeding that will not stop, or bruising with no cause.
• Small flat red spots under the skin.
• New shortness of breath, chest pain, or confusion.
• Rapid weight gain or swelling of the abdomen while on treatment.

There is no screening program for AML. It is found through blood tests, usually prompted by symptoms.

How CD33 status is established

Nobody receives this drug without a laboratory result. Diagnosis of AML uses tests of the blood and bone marrow. A bone marrow sample is taken and examined by a pathologist.

The same sample is then tested for cell surface markers, including CD33, and for gene changes. AML is not staged the way solid tumors are. Instead the subtype, the marker profile, and the gene changes define the risk group and the treatment plan.

Induction, consolidation, and supportive care

NCI describes AML treatment in two phases. Remission induction therapy comes first, aiming to clear leukemia cells from blood and bone marrow. Consolidation therapy follows, aiming to kill cells that remain and could cause relapse. Gemtuzumab ozogamicin is dosed across both phases.

Supportive care runs throughout. Myelosuppression, meaning fewer red cells, white cells, and platelets, comes from the leukemia itself and from the chemotherapy. NCI lists red cell and platelet transfusions, plus antibiotics and antifungals to prevent or treat infection.

Our page on leukemia sets AML alongside the other types, and immunotherapy covers the antibody-based approaches this drug borrows from.

Where AML outcomes stand

These SEER figures describe the whole US population and predict nothing for one person.

For acute myeloid leukemia, five-year relative survival is 33.4 percent for cases from 2016 to 2022. An estimated 22,720 new cases and 11,500 deaths are projected for 2026. Median age at diagnosis is 70. AML is not staged like a solid tumor, so SEER publishes no stage breakdown for it.

The long trend is worth seeing next to that figure. In 1975 the five-year relative survival recorded by SEER was 5.45 percent.

What the withdrawal teaches

Accelerated approval trades certainty for speed. A drug reaches patients sooner, on evidence that is reasonably likely to predict benefit, and the sponsor must then confirm that benefit.

Sometimes it does not confirm. The FDA maintains a public list of cancer accelerated approvals that were withdrawn, and this drug is on it. That list is not a scandal. It is the system doing the second half of its job.

What this approval cannot tell you

The current label is a different proposition from the 2000 one: a different dose schedule, a wider age range, and a defined place inside combination chemotherapy. Whether it fits one person depends on CD33 status, age, liver function, other treatments, and the risk group the leukemia falls into.

Sources

• FDA, Withdrawn: Cancer Accelerated Approvals — https://www.fda.gov/drugs/resources-information-approved-drugs/withdrawn-cancer-accelerated-approvals
• DailyMed, MYLOTARG (gemtuzumab ozogamicin) label, Initial U.S. Approval 2000 — https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=32fd2bb2-1cfa-4250-feb8-d7956c794e05
• NCI, Gemtuzumab Ozogamicin — https://www.cancer.gov/about-cancer/treatment/drugs/gemtuzumabozogamicin
• NCI PDQ, Acute Myeloid Leukemia Treatment (Patient Version) — https://www.cancer.gov/types/leukemia/patient/adult-aml-treatment-pdq
• SEER Cancer Stat Facts, Acute Myeloid Leukemia — https://seer.cancer.gov/statfacts/html/amyl.html

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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