SAFETY
Indication: NINLARO® (ixazomib) 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.
Warnings and Precautions
- Warnings and Precautions associated with NINLARO include thrombocytopenia, gastrointestinal toxicities, peripheral neuropathy, peripheral edema, cutaneous reactions, thrombotic microangiopathy, hepatotoxicity, embryo-fetal toxicity, and Increased Mortality in Patients Treated with NINLARO in the Maintenance Setting
- For additional details about these Warnings and Precautions, see the Important Safety Information below.
Selected safety profile
| NINLARO+Rd* (n=361) | Rd* (n=359) | |||||
|---|---|---|---|---|---|---|
| AR | All grades | Grade 3 | Grade 4 | All grades | Grade 3 | Grade 4 |
| Diarrhea | 52% | 10% | 0 | 43% | 3% | 0 |
| Constipation | 35% | <1% | 0 | 28% | <1% | 0 |
| Peripheral neuropathies† | 32% | 2% | 0 | 24% | 2% | 0 |
| Nausea | 32% | 2% | 0 | 23% | 0 | 0 |
| Edema peripheral | 27% | 2% | 0 | 21% | 1% | 0 |
| Back pain‡ | 27% | <1% | 0 | 24% | 3% | 0 |
| Rash† | 27% | 3% | 0 | 16% | 2% | 0 |
| Upper respiratory tract infection‡ | 27% | 1% | 0 | 23% | 1% | 0 |
| Vomiting | 26% | 1% | 0 | 13% | <1% | 0 |
| Bronchitis | 22% | 2% | 0 | 17% | 2% | <1% |
Additional safety information
- Serious ARs reported in ≥2% of patients included diarrhea (3%), thrombocytopenia (2%), and bronchitis (2%)1
- Incidence of thrombocytopenia in patients in the NINLARO and Rd regimens, respectively: any grade, 85% vs 67%; grades 3-4, 30% vs 14%1
- Incidence of neutropenia in the NINLARO and Rd regimens, respectively: any grade, 74% vs 70%; grades 3-4, 34% vs 37%1
- *The NINLARO regimen included NINLARO+lenalidomide+dexamethasone. The Rd regimen included placebo+lenalidomide+dexamethasone.
- †Represents a pooling of preferred terms.
- ‡At the time of the final analysis, these adverse reactions no longer met the criterion for a ≥ 5% difference between the NINLARO + Rd regimen and Rd regimen.
- AR=adverse reaction.
The NINLARO® (ixazomib) regimen demonstrated a safety profile appropriate to treatment to disease progression1
Safety in high-risk† patient population
- The overall safety profiles in the high-risk and standard-risk cytogenetics patients in each group are consistent with data reported for the overall population8
- As seen in the overall population, in both high-risk and standard-risk cytogenetics patients, common adverse events were primarily of grade 1 or 2 severity and included diarrhea, constipation, neutropenia, and anemia8
- *The NINLARO regimen included NINLARO+lenalidomide+dexamethasone. The Rd regimen included placebo+lenalidomide+dexamethasone.
- †Defined as patients with del(17p), t(4;14), and/or t(14;16).
The majority of patients continued at the starting dose of NINLARO without dose reduction7
of patients receiving the NINLARO regimen in TOURMALINE-MM1 continued on their starting NINLARO dose
- The median dose intensity for NINLARO and placebo was high and similar in the NINLARO and Rd regimens‡: 97.4% and 98.2%, respectively
- Relative dose intensity was calculated as 100 x (total amount of dose taken/total planned dose over treated cycles)
- ‡The NINLARO regimen included NINLARO+lenalidomide+dexamethasone. The Rd regimen included placebo+lenalidomide+dexamethasone.
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%).