What is ixazomib (Ninlaro®)?
Ixazomib is the first oral proteasome inhibitor used to treat adults with myeloma. It is prescribed together with lenalidomide and dexamethasone in adults with relapsed or refractory myeloma who has received at least one prior treatment. The Food and Drug Administration (FDA) approved it in the US in November 2015. In September 2016, the European Medicines Agency (EMA) granted conditional approval. This means that the drug has been authorised for marketing under the condition that the company collect further information about the risks and benefits of this drug.
How does ixazomib work?
Ixazomib targets a part of cells called proteasomes. It works by slowing down or blocking proteasomes from doing their job of digesting proteins when they are no longer needed in normal cells. In myeloma, blocking this natural process can actually help. When the proteins in myeloma cells are not broken down, the cancer cells are damaged and they eventually die.
What are the benefits of ixazomib?
Ixazomib has been proven in a study to help some patients live longer without their myeloma getting worse.
A clinical trial of 722 people whose myeloma had come back or stopped responding to prior therapy compared ixazomib with a placebo (a dummy treatment), both taken together with lenalidomide and dexamethasone. It measured the length of time a patient lived without their disease getting worse (progression-free survival).
The combination of ixazomib plus lenalidomide and dexamethasone increased the length of progression-free survival by about six months, or 40 per cent.
Ixazomib is currently being studied in clinical trials in relapsed and/or refractory myeloma, in newly diagnosed patients, and as maintenance therapy.
What are the side effects?
The most common side effects in the clinical trial were:
- thrombocytopaenia (low blood platelet counts)
- peripheral neuropathy (nerve damage in the hands and feet causing tingling or numbness)
- peripheral oedema (swelling, especially of the ankles and feet),
- back pain
Serious adverse reactions reported in ≥ 2% of patients included low blood platelet counts (2%) and diarrhoea (2%).
How and when is ixazomib given?
Ixazomib is taken along with lenalidomide and dexamethasone. It is available as capsules (2.3, 3 and 4 mg) to be taken at least one hour before or two hours after food. The initial recommended dose is 4 mg. This is taken once a week (on the same day of the week) for 3 weeks in a row followed by a week with no ixazomib treatment (for example days 1, 8, and 15 of a 28-day treatment cycle). This 4-week cycle should be continued until the disease gets worse or side effects become unacceptable.
People taking ixozomib should avoid taking strong CYP3A inducers (such as rifampin, phenytoin, carbamazepine, and St. John’s Wort).
- The Multiple Myeloma Research Foundation (MMRF). https://www.themmrf.org/multiple-myeloma-knowledge-center/myeloma-drugs-guide/ninlaro-ixazomib
- Food and Drug Administration. Approved Drugs. https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm473804.htm
- Manufacturer’s product information. https://www.ninlaro.com/patient-information.pdf
- European Medicines Agency. Ninlaro (ixazomib) European public assessment report (EPAR) – last updated 07/12/2016