Multiple Myeloma Treatment Trends

Multiple myeloma is complex, and continuous therapy has been shown to improve outcomes.^1-3

CONTINUOUS THERAPY VS FIXED DURATION THERAPY

Continuous therapy doubled median PFS vs fixed-duration therapy³
Results from Palumbo et al pooled analysis of three phase 3 studies^*

Chart showing that continuous therapy doubled median PFS vs fixed-duration therapy. PFS was 16 months with fixed-duration therapy, and 32 months with continuous therapy. Results from Palumbo et al pooled analysis of three phase 3 studies. — Adapted from Palumbo et al, 2015.³
*Patients received ASCT and/or immunomodulatory drugs in various combinations with proteasome inhibitors, chemotherapy, or CSTs.⁴
ASCT=autologous stem-cell transplantation; CI=confidence interval; CST=corticosteroid therapy; CT=continuous treatment; FDT=fixed-duration treatment: HR=hazard ratio; PFS=progression-free survival.

Proteasome inhibition remains a cornerstone of multiple myeloma treatment with optimal outcomes^1,5

Proteasome inhibition has been a standard of care in the treatment of multiple myeloma for >15 years⁵
Triplet regimens, including those containing a PI, have demonstrated superior efficacy vs doublet regimens^1,2

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) recommend triplet regimens for patients with multiple myeloma²

NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

Treatment with injectable PIs can be difficult to continue because of⁶:

Adverse Reactions^7,8

Burden of Repeated IV or SQ Administration Impacting Patients' HRQOL⁹

Restricted Mobility⁹

Desire to Remain Outside of a Hospital or Clinic⁹

HRQOL=health-related quality of life; IV=intravenous; SC=subcutaneous.

NINLARO patient profiles

Different patient types with relapsed multiple myeloma may benefit from the NINLARO triplet regimen.

Discover Appropriate Patients

NINLARO clinical trial data

The TOURMALINE-MM1 clinical trial evaluated efficacy and safety of the all-oral NINLARO regimen vs Rd regimen in relapsed patients with multiple myeloma.

Find Trial Results

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. Stevens-Johnson syndrome and toxic epidermal necrolysis, including fatal cases, have been reported with NINLARO. If Stevens-Johnson syndrome or toxic epidermal necrolysis 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.

Multiple Myeloma Treatment Trends

CONTINUOUS THERAPY VS FIXED DURATION THERAPY

Continuous therapy doubled median PFS vs fixed-duration therapy³
Results from Palumbo et al pooled analysis of three phase 3 studies^*

Proteasome inhibition remains a cornerstone of multiple myeloma treatment with optimal outcomes^1,5

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) recommend triplet regimens for patients with multiple myeloma²

Treatment with injectable PIs can be difficult to continue because of⁶:

NINLARO patient profiles

NINLARO clinical trial data

IMPORTANT SAFETY INFORMATION, INDICATION, AND USAGE

WARNINGS AND PRECAUTIONS

ADVERSE REACTIONS

DRUG INTERACTIONS:

USE IN SPECIFIC POPULATIONS

INDICATION AND USAGE

CONTINUOUS THERAPY VS FIXED DURATION THERAPY

Continuous therapy doubled median PFS vs fixed-duration therapy3 Results from Palumbo et al pooled analysis of three phase 3 studies*

Proteasome inhibition remains a cornerstone of multiple myeloma treatment with optimal outcomes1,5

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend triplet regimens for patients with multiple myeloma2

Treatment with injectable PIs can be difficult to continue because of6:

NINLARO patient profiles

NINLARO clinical trial data

IMPORTANT SAFETY INFORMATION, INDICATION, AND USAGE

Continuous therapy doubled median PFS vs fixed-duration therapy³
Results from Palumbo et al pooled analysis of three phase 3 studies^*

Proteasome inhibition remains a cornerstone of multiple myeloma treatment with optimal outcomes^1,5

NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) recommend triplet regimens for patients with multiple myeloma²

Treatment with injectable PIs can be difficult to continue because of⁶: