MYLOTARG

What it is

MYLOTARG contains gemtuzumab ozogamicin . It is a powder for injection . Each single-dose vial contains 5 mg gemtuzumab ozogamicin . Gemtuzumab ozogamicin is a CD33-directed antibody–drug conjugate comprised of a humanised immunoglobulin class G subtype 4 (IgG4) antibody which specifically recognises human CD33 . This medicinal product is subject to additional monitoring in Australia .

Approved indications

— Combination therapy with standard anthracycline 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) .

Dosing overview

The recommended dose of MYLOTARG is 3 mg/m² per dose (up to a maximum of one 5 mg vial) infused over a 2-hour period on Days 1, 4, and 7 of the induction chemotherapy cycle . If a second induction is required, MYLOTARG should not be administered during second induction therapy; only standard anthracycline and cytarabine should be administered during the second induction cycle . For patients experiencing a complete remission following induction, the recommended dose of MYLOTARG is 3 mg/m² per dose (up to a maximum dose of one 5 mg vial) infused over a 2-hour period on Day 1 of the consolidation chemotherapy cycle .

Key safety warnings

Hepatotoxicity, including life-threatening and sometimes fatal hepatic venoocclusive disease/sinusoidal obstruction syndrome (VOD/SOS) events, was reported in association with the use of MYLOTARG as a single agent and as part of a combination chemotherapy regimen, in patients without a history of liver disease or haematopoietic stem cell transplant . Monitor closely for signs and symptoms of VOD/SOS; these may include elevations in alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin, and alkaline phosphatase, which should be monitored prior to each dose of MYLOTARG, hepatomegaly (which may be painful), rapid weight gain, and ascites . In clinical studies with MYLOTARG, infusion-related reactions, including anaphylaxis were reported, and there have been reports of fatal infusion reactions in the postmarketing setting . Signs and symptoms of infusion-related reactions may include fever and chills, and less frequently hypotension, tachycardia, and respiratory symptoms that may occur during the first 24 hours after administration . Premedication with a corticosteroid, antihistamine, and acetaminophen (or paracetamol) is recommended 1 hour prior to MYLOTARG dosing to help ameliorate infusion-related symptoms . In clinical studies with MYLOTARG, neutropenia, thrombocytopenia, anaemia, leukopenia, febrile neutropenia, lymphopenia, and pancytopenia, some of which were life-threatening or fatal, were reported; complications associated with neutropenia and thrombocytopenia may include infections and bleeding/haemorrhagic events, respectively, and these were reported with some being life-threatening or fatal . Monitor complete blood counts prior to each dose of MYLOTARG and monitor patients for signs and symptoms of infection, bleeding/haemorrhage, or other effects of myelosuppression during treatment . In clinical studies with MYLOTARG, tumour lysis syndrome was reported, and fatal reports of tumour lysis syndrome complicated by acute renal failure have been reported in the postmarketing setting . Appropriate measures to help prevent the development of tumour lysis-related hyperuricaemia such as hydration, administration of antihyperuricaemic agents (for example, allopurinol) or other agents for treatment of hyperuricaemia (for example, rasburicase) must be taken .

Contraindications

MYLOTARG is contraindicated in patients with hypersensitivity to the active substance or to any of the excipients .

PBS listing

MYLOTARG 5 mg powder for injection is listed on the PBS with 4 items, authority required restriction, and an ex-manufacturer price of A$9167.00 .

Regulatory history

MYLOTARG gemtuzumab ozogamicin 5 mg powder for injection vial was first listed on the ARTG on 2020-04-09 . The TGA approved MYLOTARG on 2020-04-08 for combination therapy with standard anthracycline and cytarabine for the treatment of patients age 15 years and above with previously untreated, de novo CD33-positive acute myeloid leukaemia, except acute promyelocytic leukaemia . In March 2021, the PBAC recommended against MYLOTARG for acute myeloid leukaemia in patients with an unfavourable cytogenetic profile and for de novo CD33-positive AML generally; in November 2021, the PBAC recommended MYLOTARG for acute myeloid leukaemia .