KYPROLIS

What it is

Kyprolis is a modified tetrapeptidyl epoxide supplied as powder for injection for intravenous infusion. Kyprolis is available as a single-use vial containing 10 mg, 30 mg or 60 mg of carfilzomib. Kyprolis is supplied as a sterile, white to off-white lyophilised powder.

Approved indications —

Relapsed or refractory multiple myeloma in patients who have received at least one prior therapy, in combination with dexamethasone. — Relapsed or refractory multiple myeloma in patients who have received at least one prior therapy, in combination with lenalidomide and dexamethasone. — Relapsed or refractory multiple myeloma in patients who have received at least one prior therapy, in combination with daratumumab and dexamethasone. — Relapsed or refractory multiple myeloma in patients who have received at least one prior therapy, in combination with isatuximab and dexamethasone.

Dosing overview

Kyprolis is administered intravenously as a 10 minute or a 30 minute infusion either once or twice weekly based on the selected regimen. The dose is calculated using the patient's baseline body surface area. Patients with a body surface area greater than 2.2 m² should receive a dose based upon a body surface area of 2.2 m². Treatment may be continued until disease progression or until unacceptable toxicity occurs.

Key safety warnings

New or worsening cardiac failure, myocardial ischaemia and infarction have occurred following administration of Kyprolis. Death due to cardiac arrest has occurred within a day of Kyprolis administration and fatal outcomes have been reported with cardiac failure and myocardial infarction. The risk of cardiac failure is increased in elderly patients aged 75 years and over, and in Asian patients. Acute respiratory distress syndrome, acute respiratory failure and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving Kyprolis. Some of these events have been fatal. Pulmonary hypertension has been reported in patients treated with Kyprolis. Some of these events have been fatal. Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with Kyprolis. Some of these events have been fatal. Cases of acute renal failure have been reported in patients administered Kyprolis. Some of these events have been fatal. Tumour lysis syndrome has been reported with Kyprolis use, including some fatal cases. Patients with a high tumour burden should be considered to be at greater risk for tumour lysis syndrome. There have been cases of haemorrhage such as gastrointestinal, pulmonary and intracranial haemorrhage reported in patients treated with Kyprolis, often associated with thrombocytopenia. Some of these events have been fatal. There have been cases of hepatic failure, including fatal cases, reported in patients administered Kyprolis. Since Kyprolis can cause elevations of serum transaminases, liver enzymes should be monitored regularly, regardless of baseline values.

Contraindications

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

PBS listing

Kyprolis 30 mg powder for injection is listed on the PBS with a streamlined restriction at an ex-manufacturer price of A$602.75.

Regulatory history

Kyprolis was first registered on the ARTG on 19 December 2016 for the 30 mg and 60 mg powder for injection vials, with the 10 mg vial registered on 27 February 2018. In November 2014, Kyprolis was not recommended by the PBAC for treatment of relapsed and refractory multiple myeloma due to uncertain clinical benefit and high cost. In July 2017, the PBAC recommended Kyprolis for use in combination with dexamethasone in patients with relapsed or refractory multiple myeloma, based on superior comparative effectiveness over bortezomib in combination with dexamethasone. In March 2018, a Section 100 listing was approved for the 10 mg vial form, in July 2020 the once weekly 70 mg/m² dosing regimen was added, and in March 2022 the combination with lenalidomide and dexamethasone was recommended. An AusPAR was issued on 17 February 2023 approving an extension of indications for Kyprolis for treatment of patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.