Ninlaro®

What is Ninlaro?

Ninlaro, also known as ixazomib, is a second-generation proteasome inhibitor in the same class of drugs as Velcade (bortezomib, Takeda Oncology) and Kyprolis (carfilzomib, Amgen). Ninlaro is manufactured by Takeda Oncology.

The Multiple Myeloma Research Consortium (MMRC) played an integral role in the development of Ninlaro, facilitating a clinical trial for newly diagnosed patients that studied Ninlaro in combination with Revlimid (lenalidomide, Celgene) and dexamethasone. The MMRC has initiated six additional trials examining Ninlaro in patients with relapsed or refractory myeloma; as maintenance therapy following autologous stem cell transplant; and as a treatment for patients with plasma cell leukemia or extramedullary disease..


How is Ninlaro used?

Ninlaro is approved for use in combination with Revlimid and low-dose dexamethasone (IRd) for patients with multiple myeloma who have received at least one prior therapy.

What types of patients can benefit from Ninlaro?

Ninlaro has been studied in a variety of patients with multiple myeloma, including:

  • Patients who received one or two prior therapies
  • Patients who have received three or more prior therapies (heavily pretreated)
  • Patients who were refractory to their previous treatment(s)
  • Patients who previously received high-dose chemotherapy and stem cell transplant
  • Both younger and older patients
  • Patients with reduced liver function (hepatic impairment)
  • Patients with reduced kidney function (renal impairment) and patients on dialysis

How does Ninlaro work?

Proteasomes are proteins found in cells, and they play an important role in regulating cell function and cell growth. Ninlaro disrupts a cancer cell’s ability to survive by blocking the proteasome and disrupting protein metabolism. Myeloma cells may be uniquely sensitive to proteasome inhibitors.

Laboratory and animal studies show that Ninlaro inhibits the growth of myeloma cells, including those that are resistant to Velcade and other anti-myeloma therapies. Ninlaro also induces myeloma cell death (apoptosis


How is Ninlaro administered?

Ninlaro is an oral medication that is available as 4 mg, 3 mg, and 2.3 mg capsules.

The recommended starting dose of Ninlaro is 4 mg once a week on days 1, 8, and 15 of each 4-week cycle along with Revlimid and dexamethasone.

Patients with moderately or severely reduced liver function (hepatic impairment) or kidney function (renal impairment) and patients receiving dialysis  typically receive a lower (3 mg) starting dose of Ninlaro.

Revlimid (25 mg) is taken daily on days 1 to 21 of each cycle and dexamethasone (40 mg) is taken on days 1, 8, 15, and 22 of each cycle. In addition, a blood thinner such as aspirin is typically taken along with Revlimid-dexamethasone to reduce the chance of developing a blood clot.

Patients receive IRd until the multiple myeloma progresses or they experience unacceptable side effects.

Ninlaro should be taken with water once a week on the same day and at approximately the same time. It should be taken at least 1 hour before or at least 2 hours after eating, separately from dexamethasone, which should be taken with food.

If you are late in taking a dose of Ninlaro or you miss a dose, take this dose if your next scheduled dose is at least 72 hours (3 days) away. Do not take this dose if your next dose is scheduled within 3 days. Do not take a double dose to make up for a missed dose.

If you vomit after taking Ninlaro, do not take another dose. Wait until your next scheduled dose to resume Ninlaro


What are Ninlaro side effects?

The most common side effects seen in a clinical study with IRd included:

  • Gastrointestinal effects (diarrhea, constipation, nausea, or vomiting)
  • Low white blood cell count (neutropenia) or platelet count (thrombocytopenia)
  • Pain, numbness, or tingling in hands and feet (peripheral neuropathy)
  • Swelling of the hands or feet (peripheral edema)
  • Back pain

In this study, the most common serious side effects included:

  • Low white blood cell count (neutropenia) or platelet count (thrombocytopenia)
  • Diarrhea

Women should avoid becoming pregnant while taking Ninlaro, as it caused fetal harm in animal studies.

How are side effects of Ninlaro managed?

Patients who experience new or worsening side effects should contact their health care provider. Most side effects can be managed with supportive care measures, other medications, temporarily stopping treatment, or dose modifications.

Patients who experience low platelet or neutrophil counts may have their next dose of Ninlaro and Revlimid held until their counts go back up. At that point, Revlimid is resumed at a lower dose (according to its recommended prescribing information) and the same dose of Ninlaro is taken. Patients experiencing neutropenia may also receive medication to stimulate the production of neutrophils.

If the platelet or neutrophil counts fall again, both Ninlaro and Revlimid are again withheld until the counts go up. Ninlaro is then resumed at a lower dose and Revlimid is resumed at its most recent dose. For any subsequent instances of low platelet or neutrophil counts, any dosing modifications will alternate between Revlimid and Ninlaro.

Patients who experience side effects such as rash, peripheral neuropathy, or other severe toxicities may also have their next dose of Ninlaro and/or Revlimid held until the symptoms improve. When dosing is resumed, one agent may be administered at a lower dose, depending on the side effect seen. IRd may be stopped in cases of life-threatening or disabling side effects.


What have Ninlaro clinical trials shown?

  • Ninlaro has been evaluated alone and in combination with other myeloma agents in both relapsed and/or refractory multiple myeloma and newly diagnosed disease.

    Patients Who Have Received at Least One Prior Therapy

    The approval of Ninlaro was based on results from the phase 3 TOURMALINE-MM1 trial, which included patients with relapsed and/or refractory multiple myeloma who had received one to three prior therapies. In this trial 722 patients received IRd or Revlimid-low-dose dexamethasone alone (Rd).

    On average, patients receiving IRd lived significantly longer without their disease worsening compared to patients receiving Rd (20.6 months vs 14.7 months).

    How is Ninlaro currently being studied in myeloma?

    Ninlaro is being evaluated in several phase 3 clinical trials in the U.S. in relapsed and/or refractory myeloma, in newly diagnosed disease, and as maintenance therapy.

    • A comparison of Ninlaro-dexamethasone to Pomalyst (pomalidomide, Celgene)-dexamethasone in relapsed/refractory MM (NCT03170882)
    • In combination with Revlimid and dexamethasone (IRd) in patients with newly diagnosed myeloma (TOURMALINE-MM2; NCT01850524)
    • As maintenance therapy in patients who have achieved a partial response or better to their initial therapy and who have (NCT02181413) or have not undergone autologous stem cell transplantation (ASCT) (NCT02312258)

    Interested in learning more about Ninlaro clinical trials? Talk to an MMRF Nurse Patient Navigator  to learn more or use our clinical trials finder:

    FIND CLINICAL TRIALS

    Updated April 2019

    Please visit the sponsor’s official patient site for up-to-date information on Ninlaro.