NINLARO® (ixazomib): Durable Strength When Navigating the Difficulties of Multiple Myeloma in the Real World1-5

INDICATION AND USAGE

Indication: NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Limitations of Usage: NINLARO is not recommended for the use of the maintenance setting or in newly diagnosed multiple myeloma in combination with lenalidomide and dexamethasome outside of controlled clinical trials.

Please see Important Safety Information below and full Prescribing Information.
INDICATION AND USAGE

Indication: NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.

Limitations of Usage: NINLARO is not recommended for use in the maintenance setting or in newly diagnosed multiple myeloma in combination with lenalidomide and dexamethasone outside of controlled clinical trials.

IMPORTANT SAFETY INFORMATION
WARNINGS AND PRECAUTIONS

  • Thrombocytopenia Thrombocytopenia has been reported with NINLARO. Platelet nadirs typically occurred between Days 14-21 of each 28-day cycle and recovered to baseline by the start of the next cycle. Grade 3 thrombocytopenia was reported in 17% of patients in the NINLARO regimen and Grade 4 thrombocytopenia was reported in 13% in the NINLARO regimen. During treatment, monitor platelet counts at least monthly, and consider more frequent monitoring during the first three cycles. Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines.
  • Gastrointestinal Toxicities, including diarrhea, constipation, nausea and vomiting were reported with NINLARO and may occasionally require the use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea resulted in the discontinuation of one or more of the three drugs in 3% of patients in the NINLARO regimen and 2% of patients in the placebo regimen. Adjust dosing for Grade 3 or 4 symptoms.
  • Peripheral Neuropathy was reported with NINLARO. The most commonly reported reaction was peripheral sensory neuropathy (24% and 17% in the NINLARO and placebo regimens, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (<1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 4% of patients in the NINLARO regimen and <1% of patients in the placebo regimen. During treatment, monitor patients for symptoms of neuropathy and consider adjusting dosing for new or worsening peripheral neuropathy.
  • Peripheral Edema was reported with NINLARO. Evaluate for underlying causes and provide supportive care, as necessary. Adjust dosing of NINLARO for Grade 3 or 4 symptoms or dexamethasone per its prescribing information.
  • Cutaneous Reactions: including a fatal case of Stevens-Johnson syndrome, were reported with NINLARO. If Stevens-Johnson syndrome occurs, discontinue NINLARO and manage as clinically indicated. Rash, most commonly maculo-papular and macular rash, was reported with NINLARO. Rash resulted in discontinuation of one or more of the three drugs in <1% of patients in both regimens. Manage rash with supportive care or with dose modification if Grade 2 or higher.
  • Thrombotic Microangiopathy: has been reported with NINLARO. Fatal cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/ hemolytic uremic syndrome (TTP/HUS), have been reported in patients who received NINLARO. Monitor for signs and symptoms of TTP/HUS. If the diagnosis is suspected, stop NINLARO and evaluate. If the diagnosis of TTP/HUS is excluded, consider restarting NINLARO. The safety of reinitiating NINLARO therapy in patients previously experiencing TTP/HUS is not known.
  • Hepatotoxicity has been reported with NINLARO. Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in <1% of patients treated with NINLARO. Hepatotoxicity has been reported (10% in the NINLARO regimen and 9% in the placebo regimen). Monitor hepatic enzymes regularly and adjust dosing for Grade 3 or 4 symptoms.
  • Embryo-fetal Toxicity: NINLARO can cause fetal harm. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective non-hormonal contraception during treatment with NINLARO and for 90 days following the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with NINLARO and for 90 days following the last dose.
  • Increased Mortality in Patients Treated with NINLARO in the Maintenance Setting: In two prospective randomized clinical trials in multiple myeloma in the maintenance setting, treatment with NINLARO resulted in increased deaths. Treatment of patients with NINLARO for multiple myeloma in the maintenance setting is not recommended outside of controlled trials.
ADVERSE REACTIONS

The most common adverse reactions (≥ 20%) in the NINLARO regimen compared to placebo in combination with lenalidomide plus dexamethasone, respectively were thrombocytopenia (85%, 67%; pooled from adverse event and laboratory data), neutropenia (74%, 70%; pooled from adverse event and laboratory data), diarrhea (52%, 43%), constipation (35%, 28%), peripheral neuropathy (32%, 24%), nausea (32%, 23%), edema peripheral (27%, 21%), rash (27%, 16%), vomiting (26%, 13%), and bronchitis (22%, 17%). Serious adverse reactions reported in ≥ 2% of patients in the NINLARO regimen included diarrhea (3%), thrombocytopenia (2%), and bronchitis (2%).

DRUG INTERACTIONS: Avoid concomitant administration of NINLARO with strong CYP3A inducers.
USE IN SPECIAL POPULATIONS
  • Lactation: Advise women not to breastfeed during treatment with NINLARO and for 90 days after the last dose.
  • Hepatic Impairment: Reduce the NINLARO starting dose to 3 mg in patients with moderate or severe hepatic impairment.
  • Renal Impairment: Reduce the NINLARO starting dose to 3 mg in patients with severe renal impairment or end-stage renal disease requiring dialysis. NINLARO is not dialyzable.

Please see NINLARO (ixazomib) full Prescribing Information.

Speaker Information:

Dr. Ehsan Malek

Dr. Ehsan Malek

Assistant Professor
Case Comprehensive Cancer Center Director, Multiple Myeloma Program

M.Yair Levy, MD

M.Yair Levy, MD

Director, Hematology
Malignancies Research
Baylor University Medical Center

Program Objectives

discuss

Discuss

how real-world evidence may be leveraged to complement clinical trial results

discuss

Review

NINLARO® (ixazomib) clinical efficacy and safety data from TOURMALINE-MM1 trial

discuss

Explore

real-world evidence for NINLARO® (ixazomib)

References: 1. NINLARO (ixazomib) (prescribing information). Cambridge, MA: Takeda Pharmaceutical Company Limited; March 2021.2. Moreau P et al. N Engl J Med. 2016;374(17):1621-1634. 3. Terpos E, et al. Ann Hematol. 2020;99:1049-1061. 4. Hájek R, et al. [published online March 26, 2021]. Future Oncol. doi:10.2217/fon-2020-1225. 5. Minarik J, et al. BMC Cancer. 2021;21:73.