c steatosis, hepatitis cholestatic, and hepatotoxicity have each been reported in <1% of patients taking ixazomib. Patients receiving ixazomib should be tested for hepatic enzymes regularly, and the ixazomib dose should be adjusted if grade 3 or 4 events are observed.
Specific Populations
Pregnancy
Ixazomib can cause fetal harm when administered during pregnancy. Women should avoid becoming pregnant while taking ixazomib.Females of reproductive potential should be advised to use effective contraception during treatment with ixazomib and for 90 days after the final dose.
Lactation
It is not known whether ixazomib or its metabolites are present in human milk. Women taking ixazomib should discontinue nursing.
Men and women of reproductive potential
Effective contraceptives should be used while taking ixazomib and for 90 days after treatment with ixazomib.
Pediatric use
The safety and effectiveness of ixazomib have not been established in children.
Geriatric use
Of the patients with multiple myeloma in clinical studies of ixazomib, 55% were aged ≥65 years and 17% were aged ≥75 years.No differences in safety were observed between the younger and older cohorts.
Hepatic impairment
In patients with moderate or severe hepatic impairment, blood levels of ixazomib increased by 20% compared with patients with normal liver function.The starting dose of ixazomib should be reduced in this patient population.
Renal impairment
In patients with severe renal impairment or end-stage renal disease requiring dialysis, blood levels of ixazomib increased by 39% compared with normal renal function.12 The starting dose of ixazomib should be reduced in this patient population. Because ixazomib is not dialyzable, it can be administered without regard to dialysis timing.12
Conclusion
Ixazomib is the first oral proteasome inhibitor to demonstrate clinical benefit and an acceptable safety profile in patients with relapsed or refractory multiple myeloma. The TOURMALINE-MM1 study demonstrated that adding ixazomib to lenalidomide and dexamethasone significantly enhanced PFS compared with placebo plus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. The combination of ixazomib plus lenalidomide and dexamethasone represents the first all-oral triple therapy for patients with relapsed or refractory multiple myeloma.
In addition to the TOURMALINE-MM1 clinical trial, 4 global phase 3 trials are ongoing for ixazomib, including TOURMALINE-AL1, ixazomib plus dexamethasone in patients with relapsed or refractory amyloid light-chain amyloidosis; TOURMALINE-MM2, ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with newly diagnosed multiple myeloma; TOURMALINE-MM3, ixazomib versus placebo as maintenance therapy in patients with newly diagnosed multiple myeloma after induction therapy and autologous stem-cell transplantation; and TOURMALINE-MM4, ixazomib versus placebo as maintenance therapy in patients with newly diagnosed multiple myeloma who have not undergone autologous stem-cell transplantation.
临床试验结果
此次获批是基于一项国际、随机、双盲临床试验的结果。该试验共纳入722例多发性骨髓瘤复发患者。受试者分别接受Ninlaro+来那度胺+地塞米松和安慰剂+来那度胺+地塞米松治疗。与服用安慰剂的患者相比，服用了Ninlaro的患者的无疾病恶化期更长，分别为14.7个月和20.6个月。
武田Ninlaro（ixazomib）-为FDA批准第三个治疗多发性骨髓瘤创新药物
2015年11月23日，由日本制药巨头武田（Takeda）开发的一款口服抗癌药Ninlaro（ixazomib）近日喜获F |
