rm, a significant (P = .012) difference (hazard ratio, 0.74; 95% confidence interval).
The median time to response was months with ixazomib compared with 1.9 months with placebo. In the response eva luable population, the median duration of response was 20.5 months versus 15 months, respectively.
After a median follow-up of 23 months, a planned interim analysis of overall survival (OS) was conducted with 35% of the required number of deaths for the final OS analysis; an OS benefit was not demonstrated.
Adverse Events
Among patients receiving the ixazomib combination regimen in TOURMALINE-MM1, the most common adverse reactions (all grades) reported at a rate of ≥20% compared with the placebo arm included thrombocytopenia (78% vs 54%), neutropenia (67% vs 66%), diarrhea (42% vs 36%), constipation (34% vs 25%), peripheral neuropathies (a pooled term; 28% vs 21%), nausea (26% vs 21%), peripheral edema (25% vs 18%), vomiting (22% vs 11%), and back pain (21% vs 16%).
Serious adverse reactions reported in ≥2% of patients receiving the active regimen included thrombocytopenia (2%) and diarrhea (2%).For each of these adverse reactions, ≥1 of the 3 drugs was discontinued in ≤1% of patients receiving ixazomib plus lenalidomide and dexamethasone.
Various eye disorders were reported in 26% of patients receiving the ixazomib combination regimen compared with 16% of patients in the placebo arm.The most common eye disorders that were more common with ixazomib than with placebo included blurred vision (6% vs 3%, respectively), dry eye (5% vs 1%, respectively), and conjunctivitis (6% vs 1%, respectively). Grade 3 eye disorders were reported in 2% of patients receiving the ixazomib combination and in 1% of patients receiving the placebo combination.
Ixazomib does not have any contraindications.
Drug Interactions
Ixazomib should not be used concomitantly with strong cytochrome P3A inducers (ie, rifampin, phenytoin, carbamazepine, and St. John’s wort).
Warnings and Precautions
Thrombocytopenia
Platelet nadirs associated with ixazomib therapy typically occurred between days and 21 of each 28-day cycle and recovered to baseline levels by the beginning of the next cycle.The discontinuation of ≥1 of the 3 drugs in the regimen because of thrombocytopenia occurred in <1% of patients who received the ixazomib combination and in 2% of patients who received the placebo combination.
Platelet counts should be eva luated at least monthly during treatment with ixazomib.
Gastrointestinal toxicities
Diarrhea, constipation, nausea, and vomiting occasionally required the use of antidiarrheal and antiemetic medications.
Peripheral neuropathy
The majority of peripheral neuropathy reactions were grade 1 or 2.12 Grade 3 peripheral neuropathy was reported in 2% of patients receiving both regimens. Patients taking ixazomib should be monitored for symptoms of neuropathy.
Peripheral edema
The majority of peripheral edema reactions observed with ixazomib were grade 1 or 2.12 Ixazomib dosing should be adjusted if grade 3 or 4 peripheral edema occurs.
Cutaneous reactions
Grade 3 rash—typically maculopapular and macular—was reported in 3% of patients receiving ixazomib and in 1% of patients receiving placebo.Supportive care and dose modification should be considered if grade ≥2 rash occurs with ixazomib.
Hepatotoxicity
Drug-induced liver injury, hepatocellular injury, hepati |
