Gemtuzumab ozogamicin (Mylotarg)

General information

Class/mechanism: Antibody-cytotoxic agent conjugate. Gemtuzumab ozogamicin is comprised of a recombinant humanized IgG4 kappa antibody against CD33--an adhesion protein expressed on the surface of leukemic blasts and immature normal cells of myelomonocytic lineage, but not on normal hematopoietic stem cells--conjugated with a cytotoxic agent, calicheamicin. The antibody-cytotoxic agent is internalized after binding, and the calicheamicin derivative binds to DNA in the minor groove, causing DNA double strand breaks and cell death.^[1]^[2]
Route: IV
Extravasation: no information

For conciseness and simplicity, HemOnc.org currently will focus on treatment regimens and not list information such as: renal/hepatic dose adjustments, metabolism (including CYP450), excretion, monitoring parameters (although this will be considered for checklists), or manufacturer. Instead, for the most current information, please refer to your preferred pharmacopeias such as Micromedex, Lexicomp, UpToDate (courtesy of Lexicomp), or the prescribing information.^[1]

Diseases for which it is established

Acute myeloid leukemia

Diseases for which it is used

Acute promyelocytic leukemia

Patient drug information

History of changes in FDA indication

2000-05-17: Granted accelerated approval for the treatment of patients with CD33 positive acute myeloid leukemia in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. (Based on GO study 1, GO study 2, and GO study 3)
- 2011-11-28: Accelerated approval for acute myeloid leukemia withdrawn. (Based on SWOG S0106)
2017-09-01: New approval for the treatment of newly-diagnosed CD33-positive acute myeloid leukemia (AML) in adults. Gemtuzumab ozogamicin may be used in combination with daunorubicin and cytarabine for adults with newly-diagnosed AML. (Based on ALFA-0701 and EORTC/GIMEMA AML-19)
2017-09-01: New approval for treatment of relapsed or refractory CD33-positive AML in adults and in pediatric patients 2 years and older. (Based on MyloFrance-1)
2020-06-16: Approved for newly-diagnosed CD33-positive acute myeloid leukemia (AML) to include pediatric patients 1 month and older. (Approval expanded to pediatric patients 1 month and older; based on COG AAML0531)

History of changes in EMA indication

2018-04-19: Marketing authorisation (unclear if this is initial or re-authorisation)
Uncertain date: Mylotarg is indicated for combination therapy with daunorubicin (DNR) and cytarabine (AraC) for the treatment of patients age 15 years and above with previously untreated, de novo CD33-positive acute myeloid leukaemia (AML), except acute promyelocytic leukaemia (APL). (Based on ALFA-0701)

History of changes in Health Canada indication

2019-11-28: Initial notice of compliance

History of changes in PMDA indication

2005-07-25: Initial approval for the treatment of relapsing or intractable CD33 positive acute myeloid leukemia.

Also known as

Brand name: Mylotarg

References

[insert-1] 1.0 ^1.1 ^1.2 Gemtuzumab ozogamicin (Mylotarg) package insert

[2] Gemtuzumab ozogamicin (Mylotarg) package insert (locally hosted backup)

[3] Gemtuzumab ozogamicin (Mylotarg) patient drug information (Chemocare)

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