近日，武田宣布，有关口服蛋白酶体抑制剂Ninlaro（ixazomib）的一项关键性III期临床研究（TOURMALINE-MM1）的数据已发表于国际顶级医学期刊《新英格兰医学杂志》（NEJM）。该研究结果表明，Ninlaro+来那度胺+地塞米松，这种全口服三联疗法对复发性和/或难治性多发性骨髓瘤（MM）群体而言是一种有效的、可耐受的口服治疗方案，同时具有可管理的安全性。
去年底，FDA根据TOURMALINE-MM1研究的数据，批准Ninlaro联合Revlimid（lenalidomide，来那度胺）及地塞米松（dexamethasone），用于既往已接受过至少一种治疗方案的多发性骨髓瘤（MM）患者。
Ninlaro是FDA批准的首个也是唯一一个口服蛋白酶体抑制剂，之前已收获治疗复发性或难治性多发性骨髓瘤（R/R MM）的孤儿药地位和优先审查资格。Ninlaro能够阻断多发性骨髓瘤细胞的酶，进而阻碍其生长及生存的能力。此外，FDA也已授予Ninlaro治疗复发性或难治性系统性轻链淀粉样变性（AL）的突破性药物资格，这是另一种超罕见疾病。
TOURMALINE-MM1研究是一项国际性、随机、双盲、安慰剂对照III期研究，在722例复发性和/或难治性多发性骨髓瘤（MM）患者中开展，评估了Ninlaro+来那度胺+地塞米松组合疗法，相对于安慰剂+来那度胺+地塞米松组合疗法的疗效和安全性。
数据显示，与安慰剂+来那度胺+地塞米松联合治疗组相比，Ninlaro+来那度胺+地塞米松联合治疗组无进展生存期（PFS：20.6个月 vs 14.7个月，p=0.01）显著延长，更重要的是，在横跨预先设定的各亚组中均观察到PFS受益，包括预后极差的群体，如老年患者群体、既往已接受2或3种疗法的患者群体、晚期疾病患者群体，以及伴有高风险细胞遗传学异常的患者群体。
此外，Ninlaro治疗组总缓解率（ORR）为78%，至少极佳部分缓解率（VGPR）最佳部分缓解率为48%，安慰剂组分别为72%和39%。Ninlaro治疗组实现缓解的中位时间间隔为1.1个月，安慰剂组为1.9个月；Ninlaro治疗组缓解持续时间（DoR）为20.5个月，安慰剂组为15.0个月。
安全性方面，Ninlaro治疗组和安慰剂组在严重不良事件发生率（47% vs 49%）、在研究中的死亡率（4% vs 6%）相似，2组分别有74%和69%的患者经历≥3级不良事件。3级和4级血小板减少症，Ninlaro治疗组（12%和7%）发生率高于安慰剂组（5%和4%）。此外，皮疹在Ninlaro治疗组更频发（36% vs 23%），胃肠道不良反应Ninlaro治疗组略高，主要是低级不良反应。外周神经病变Ninlaro治疗组略高于安慰剂组（27% vs 22%）。
美国FDA批准Ninlaro（ixazomib）与两款其它药物合并用于治疗多发性骨髓瘤患者。Ninlaro(ixazomib)胶囊，供口服使用。推荐起始剂量4mg口服在28-天疗程的第1，8，和15天。剂量应被服用食物前至少一小时或后至少2小时。
INDICATION AND IMPORTANT SAFETY INFORMATION FOR NINLARO® (ixazomib)
Uses of NINLARO
NINLARO is a prescription medicine used to treat multiple myeloma in combination with the medicines REVLIMID® (lenalidomide) and dexamethasone, in people who have received at least one prior treatment for their multiple myeloma.
It is not known if NINLARO is safe and effective in children.
NINLARO may cause serious side effects, including:
•Low platelet counts (thrombocytopenia) are common with NINLARO and can sometimes be serious. You may need platelet transfusions if your counts are too low. Tell your healthcare provider if you have any signs of low platelet counts, including bleeding and easy bruising.
•Stomach and intestinal (gastrointestinal) problems. Diarrhea, constipation, nausea, and vomiting are common with NINLARO and can sometimes be severe. Call your healthcare provider if you get any of these symptoms and they do not go away during treatment with NINLARO. Your healthcare provider may prescribe medicine to help treat your symptoms.
•Nerve problems are common with NINLARO and may also be severe. Tell your healthcare provider if you get any new or worsening symptoms including: tingling, numbness, pain, a burning feeling in your feet or hands, or weakness in your arms or legs.
•Swelling is common with NINLARO and can sometimes be severe. Tell your healthcare provider if you develop swelling in your arms, hands, legs, ankles, or feet, or if you gain weight from swelling.
•Skin Reactions. Tell your healthcare provider if you get a new or worsening rash.
•Liver problems. Tell your healthcare provider if you get these signs of a liver problem: yellowing of your skin or the whites of your eyes; pain in your right upper-stomach area.
Back pain is also common with NINLARO.
These are not all the possible side effects of NINLARO. Talk to your healthcare provider for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
Before taking NINLARO, tell your healthcare provider about all your medical conditions, including if:
•You have liver problems or kidney problems or are on dialysis.
•You are pregnant or plan to become pregnant, as NINLARO can harm your unborn baby. Avoid becoming pregnant during treatment with NINLARO. Females, and males with a female partner who is able to become pregnant, must use effective birth control during treatment and for 90 days after the final dose of NINLARO.
•You are breastfeeding or plan to breastfeed. Do not breastfeed during treatment with NINLARO.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=fcef9088-ebab-4bd8-933f-c35f9c8bd50b