Ninlaro® (ixazomib) is an oral prescription medicine used to treat multiple myeloma in combination with the medicines Revlimid® (lenalidomide) and dexamethasone, in people who have received at least one prior treatment. It belongs to a class of drugs known as proteasome inhibitors. Ixazomib was granted orphan drug designation for MM in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. Ixazomib received "Breakthrough Therapy" status from the U.S. Food and Drug Administration (FDA) for relapsed and/or refractory AL amyloidosis in 2014.
How Does It Work?
Ninlaro (ixazomib) is the first and only oral proteasome inhibitor. Both normal cells and cancer cells contain proteasomes, enzyme complexes that break down damaged and unwanted proteins into smaller components. These smaller components are then used to create new proteins required by the cell. Proteasomes can be thought of as crucial to the cell’s “recycling” of proteins. Myeloma cells are particularly sensitive to proteasome inhibition. When their protein recycling system is shut down, myeloma cells die.
Possible Side Effects
Thrombocytopenia (low platelet count)
Thrombocytopenia is a lowered level of platelets in the blood. Platelets help blood to clot; fewer platelets can lead to bruising, bleeding, and slower healing. Both Ninlaro and Revlimid can cause platelet counts to drop. During treatment with Ninlaro. Revlimid, and dexamethasone, the platelet count reaches its lowest point on days 14–21 of each 28-day cycle, but usually recovers to baseline by the beginning of the next cycle. (For this reason, there is no Ninlaro dose during week four of each cycle.)
Diarrhea that may occur with the Ninlaro, Revlimid, and dexamethasone regimen is manageable but can be severe. Dizziness, lightheadedness, or fainting may occur due to dehydration caused by either excessive or persistent diarrhea.
Prevention is the key to managing constipation, which is defined as having fewer than three bowel movements a week. Chronic constipation is defined as infrequent bowel movements or difficult passage of stools that persists for several weeks or longer. Sometimes constipation is the flip side of diarrhea, with patients cycling back and forth between these two uncomfortable states. Talk to your healthcare providers about strategies to regulate your bowel health.
Nausea and vomiting
About one fourth of the patients in clinical trials with Ninlaro had nausea and vomiting, none of which is life-threatening. Dehydration may occur with vomiting, causing dizziness, lightheadedness, or fainting. Be sure to drink plenty of fluids. If symptoms are severe, seek medical advice. Your doctor may prescribe medication or give you intravenous (IV, or into a vein) hydration.
Peripheral neuropathy (PN) is a serious condition in which treatment affects nerves in the hands, feet, legs, and/or arms. Symptoms of PN include numbness, tingling, cramping, burning, weakness, or pain in the hands, feet, legs, and/or arms. Some patients may have experienced PN from the effects of the multiple myeloma itself and/or from previous treatments for myeloma. If you begin taking Ninlaro with peripheral neuropathy as a pre-existing condition, it is especially important that you pay attention to any increase in your discomfort. Report a worsening of your condition to your doctor immediately. If detected and managed appropriately, your neuropathy should not become worse. If these signs and symptoms are new to you, dealing with them promptly may prevent them from becoming a long-term problem.
Peripheral edema is accumulation of fluid that causes swelling, usually in the ankles, feet, and legs. This swelling is the result of the accumulation of excess fluid under the skin in the spaces within the tissues, or “interstitial” spaces.
Peripheral edema can be a side effect of long-term use of anti-inflammatory medications (such as dexamethasone), which increase fluid pressure from sodium and water retention, and thereby upset the balance of inflow and drainage of interstitial fluid. Peripheral edema can also result from many other causes, including the following:
- varicose veins,
- cardiac, kidney or liver dysfunction,
- gastrointestinal disorders,
- medications for diabetes such as insulin and pioglitazone, and
- non-steroidal anti-inflammatories such as ibuprofen and naproxen.
Usually peripheral edema affects both legs/ankles/feet. If you have swelling in one leg only, tell your healthcare team immediately. This swelling might signal the presence of a blood clot.
While most rashes that patients experience on the Ninlaro, Revlimid, anddexamethasone regimen are mild, rash can be a serious concern. It is potentially dangerous, as a rash may be mild initially and then escalate in severity. Drug rashes vary in severity from mild redness with tiny bumps over a small area to peeling of the entire skin. Rashes may appear suddenly within minutes after a person takes a drug, or they may be delayed for hours or days.
Liver toxicity (hepatotoxicity)
The liver plays an important role in transforming and clearing chemicals in the body. Medications sometimes cause harm to the liver. Signs of liver toxicity include yellowing of your skin or the whites of your eyes and/or pain in your right upper-stomach area. Your doctor will monitor your liver enzymes with regular blood tests while you're being treated with Ninlaro, Revlimid, and dexamethasone to make sure that your dose of Ninlaro is well tolerated and doesn't need to be reduced.
Some of the patients in clinical trials with the Ninlaro, Revlimid and dexamethasone experienced eye problems such as blurred vision, dry eye, and conjunctivitis (pink eye).
Based on findings with animals, Ninlaro can cause fetal harm when administered to a pregnant woman. There are no adequate or well-controlled studies in pregnant women, but studies in rats and rabbits that were exposed to the medication at slightly higher levels than those observed in patients caused embryo-fetal toxicity. Women of childbearing potential should not become pregnant while taking Ninlaro. Animal studies indicated that there were no effects due to Ninlaro on male or female reproductive organs.
NINLARO® (ixazomib) is the first and only oral medication of its kind, a proteasome inhibitor, that you can take at home. A study showed that adding NINLARO to REVLIMID® (lenalidomide) and dexamethasone improved median progression-free survival (PFS) by nearly 6 months (20.6 months with the NINLARO regimen and 14.7 months with the placebo regimen).
Takeda Oncology is committed to helping you get access to NINLARO® (ixazomib) whenever possible. NINLARO 1Point offers comprehensive programs that can assist with the financial concern, cost, and other day-to-day needs associated with your treatment.
A Study of Oral Ixazomib Citrate (MLN9708) Maintenance Therapy in Patients with Multiple Myeloma Following Autologous Stem Cell Transplant
In this phase III study, patients who have had any type of positive response to induction therapy followed by high-dose therapy with stem cell transplant will be randomly assigned by a computer to receive either a placebo (a capsule that looks like ixazomib but has no active ingredient) or ixazomib, an oral proteasome inhibitor, as maintenance therapy. This is a double-blind study, meaning that neither the patient, nor the caregiver, nor the doctor, nor those who evaluate the trial outcome know if the patient is receiving ixazomib or placebo.
Ixazomib Plus Lenalidomide and Dexamethasone Versus Placebo Plus Lenalidomide and Dexamethasone in Adult Patients with Newly Diagnosed Myeloma
A phase III multicenter study in which patients are randomly assigned by a computer to receive either a placebo (a capsule that looks like ixazomib but has no active ingredient) plus lenalidomide and dexamethasone, or ixazomib (an oral proteasome inhibitor) plus lenalidomide and dexamethasone. This is a double-blind study, meaning that neither the patient, nor the caregiver, nor the doctor, nor those who evaluate the trial outcome know which treatment regimen the patient is receiving. This trial is for patients with newly diagnosed myeloma who are not eligible for stem cell transplant.
The Oral Combination of Ixazomib with Cyclophosphamide and Dexamethasone in Patients with Newly Diagnosed or Relapsed and/or Refractory Multiple Myeloma
A phase II trial for approximately 148 patients with either newly diagnosed or relapsed and/or refractory myeloma in which response rates and safety of the all-oral combination therapy of ixazomib (an oral proteasome inhibitor), cyclophosphamide (an alkylating chemotherapy agent), and dexamethasone (a synthetic steroid) will be assessed. Newly diagnosed patients will be randomly assigned by a computer to receive one of two different dosing regimens (only the dose of cyclophosphamide will vary), and relapsed/refractory patients will be assigned to a third group.
ClinicalTrials.gov is a registry of federally and privately supported clinical trials conducted in the United States and around the world. ClinicalTrials.gov gives you information about a trial's purpose, who may participate, locations, and phone numbers for more details. This information should be used in conjunction with advice from health care professionals.