Discover how the NINLARO® (ixazomib) regimen* real-world evidence (RWE) can complement clinical trial results1-5

Download RWE Brochure

*The NINLARO regimen included NINLARO+lenalidomide+dexamethasone.1

RWE PROVIDES DATA ABOUT PATIENT OUTCOMES FROM ROUTINE CLINICAL PRACTICE

Randomized, controlled trials (RCTs) are the gold standard for measuring efficacy and safety, however:

  • Up to 72% of real-world patients with relapsed and/or refractory multiple myeloma (RRMM)† do not meet eligibility criteria for clinical trials6
  • Real-world studies include a broader range of patients with RRMM who are underrepresented in clinical trials3,7

†Receiving routine care in the United States.6

THE TOURMALINE-MM1 PIVOTAL TRIAL EVALUATED EFFICACY AND SAFETY FOR THE NINLARO REGIMEN*

TOURMALINE-MM1 was a global, phase 3, randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of NINLARO+lenalidomide+dexamethasone vs placebo+lenalidomide+dexamethasone in patients with RRMM who had received at least one prior line therapy (N=722).1,2 Explore MM1 efficacy Explore MM1 safety

*The NINLARO regimen included NINLARO+lenalidomide+dexamethasone.1

CONSISTENT EFFICACY AND SAFETY WERE DEMONSTRATED WITH THE NINLARO REGIMEN* IN 3 REAL-WORLD STUDIES1-5

Real-world study designs3-5

Terpos et al: A multicenter, retrospective analysis of NINLARO+Rd in relapsed or refractory multiple myeloma. Patients received a median of 1 prior therapy, the same as the TOURMALINE-MM1 study.

Hájek et al: A global retrospective analysis of NINLARO+Rd in patients with relapsed or refractory multiple myeloma who had received a median of 2 prior therapies vs a median of 1 prior therapy in the TOURMALINE-MM1 study.

Minařik et al: A prospective analysis of NINLARO+Rd vs Rd in relapsed or refractory multiple myeloma. Patients received a median of 1 prior therapy, the same as the TOURMALINE-MM1 study.

Consistent PFS was seen with the NINLARO regimen* in the real
world1-5

Discover results from 3 different real-world studies that evaluated RRMM patients outside of clinical trials.

ARs seen in real-world settings were consistent with the known safety profile4,5,8,9

The NINLARO regimen* demonstrated a safety profile comparable to the NINLARO arm in TOURMALINE-MM1 for patients with relapsed/refractory multiple myeloma.1-5

*The NINLARO regimen included NINLARO+lenalidomide+dexamethasone.1
ARs=adverse reactions; PFS=median progression-free survival; Rd=lenalidomide+dexamethasone.

  • Cross-trial comparisons are potentially confounded by differences in trial design and study population. Observational, retrospective analyses are not intended for direct comparison with clinical trials.6

REAL-WORLD STUDY LIMITATIONS

Real-world analyses are often nonrandomized, observational, retrospective studies that may have unobserved treatment-selection biases as well as other limitations that should be considered when comparing results with clinical trials. Outcomes should be interpreted with caution because of small sample size, limited follow-up, and limited maturity of data.4 Learn more about study limitations>

 

IMPORTANT SAFETY INFORMATION AND INDICATION

Expand+

WARNINGS AND PRECAUTIONS

  • 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 SPECIFIC 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.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-844-217-6468 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see NINLARO (ixazomib) 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 Use: 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 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 SPECIFIC 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.

To report SUSPECTED ADVERSE REACTIONS, contact Takeda Pharmaceuticals at 1-844-217-6468 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Please see NINLARO (ixazomib) 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 Use: 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.

Show References
REFERENCES: 1.NINLARO. Prescribing information. Takeda Pharmaceuticals America, Inc.; 5/2022. 2. Moreau P, Masszi T, Grzasko N, et al; for TOURMALINE-MM1 Study Group. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374(17):1621-1634. 3.Terpos E, Ramasamy K, Maouche N, et al. Real-world effectiveness and safety of ixazomib-lenalidomide-dexamethasone in relapsed/refractory multiple myeloma. Ann Hematol.2020;99(5):1049-1061. 4. Hájek R, Minařik J, Straub J, et al. Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma. Future Oncol. 2021;17(19):2499-2512. doi:10.2217/fon-2020-1225 5. Minařik J, Pika T, Radocha J, et al. Survival benefit of ixazomib, lenalidomide and dexamethasone (IRD) over lenalidomide and dexamethasone (Rd) in relapsed and refractory multiple myeloma patients in routine clinical practice. BMC Cancer. 2021;21(1):73. 6. Chari A, Romanus D, Palumbo A, et al. Randomized clinical trial representativeness and outcomes in real-world patients: comparison of 6 hallmark randomized clinical trials of relapsed/refractory multiple myeloma.Clin Lymphoma Myeloma Leuk. 2020;20(1):8-17.e16. 7. Richardson PG, San Miguel JF, Moreau P, et al. Interpreting clinical trial data in multiple myeloma: translating findings to the real-world setting. Blood Cancer J. 2018;8(11):109. 8. Hájek R, Minařik J, Straub J, et al. Ixazomib-lenalidomide-dexamethasone in routine clinical practice: effectiveness in relapsed/refractory multiple myeloma. Future Oncol, Supplemental material. Published online March 26, 2021. Accessed June 17, 2022. https://www.futuremedicine.com/doi/suppl/10.2217/fon-2020-1225 9. Data on File. Takeda Pharmaceuticals U.S.A., Inc.; 2022.