**Offer Durable Strength With the NINLARO^® (ixazomib) Regimen for Multiple Myeloma Patients at First Relapse*^1,2**

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

MM1 CLINICAL TRIAL DESIGN & RESULTS

TOURMALINE-MM1 was a global, phase 3, randomized, double-blind, placebo-controlled clinical trial that evaluated the all-oral NINLARO regimen* vs Rd regimen* in 722 patients with relapsed and/or refractory multiple myeloma who had received at least one prior line of therapy.^1,2

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

The NINLARO regimen* was shown to significantly extend PFS compared to the Rd regimen (primary analysis)*^1,2

Median PFS of 20.6 months achieved with NINLARO® (ixazomib) regimen vs 14.7 months with Rd regimen.

CI=confidence interval; HR=hazard ratio; mPFS=median progression-free survival; NE=not evaluable; PFS=progression-free survival.

Final OS Analysis
With a median follow-up of ~85 months, median OS in the ITT population was 53.6 months for patients receiving the NINLARO regimen* and 51.6 months for patients receiving the Rd regimen* (HR=0.94 [95% CI, 0.78-1.13]).¹

The NINLARO triplet regimen* demonstrated a safety profile comparable to the Rd regimen*¹

Most common adverse reactions
The most common adverse reactions (≥20%) are thrombocytopenia, neutropenia, diarrhea, constipation, peripheral neuropathy, nausea, peripheral edema, rash, vomiting, and bronchitis.¹

Serious adverse reactions
Serious ARs reported in ≥2% of patients in the NINLARO regimen* included diarrhea (3%), thrombocytopenia (2%), and bronchitis (2%).¹

Learn more about different patient profiles, like those in your practice, who may benefit from NINLARO

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EXPLORE PATIENT PROFILES

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.

**Offer Durable Strength With the NINLARO^® (ixazomib) Regimen for Multiple Myeloma Patients at First Relapse*^1,2**

MM1 CLINICAL TRIAL DESIGN & RESULTS

The NINLARO regimen* was shown to significantly extend PFS compared to the Rd regimen (primary analysis)*^1,2

The NINLARO triplet regimen* demonstrated a safety profile comparable to the Rd regimen*¹

Learn more about different patient profiles, like those in your practice, who may benefit from NINLARO

IMPORTANT SAFETY INFORMATION AND INDICATION

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

DRUG INTERACTIONS:

USE IN SPECIFIC POPULATIONS

INDICATION AND USAGE

MM1 CLINICAL TRIAL DESIGN & RESULTS

The NINLARO regimen* was shown to significantly extend PFS compared to the Rd regimen (primary analysis)*1,2

The NINLARO triplet regimen* demonstrated a safety profile comparable to the Rd regimen*1

Learn more about different patient profiles, like those in your practice, who may benefit from NINLARO

IMPORTANT SAFETY INFORMATION AND INDICATION

The NINLARO regimen* was shown to significantly extend PFS compared to the Rd regimen (primary analysis)*^1,2

The NINLARO triplet regimen* demonstrated a safety profile comparable to the Rd regimen*¹