医学
伊扎莫布
安慰剂
临床终点
内科学
多发性骨髓瘤
危险系数
外科
移植
不利影响
随机化
维持疗法
自体干细胞移植
随机对照试验
蛋白酶体抑制剂
化疗
置信区间
Carfilzomib公司
替代医学
病理
作者
Meletios A. Dimopoulos,Ivan Špıčka,Hang Quach,Albert Oriol,Roman Hájek,Mamta Garg,Meral Beksaç,Sara Bringhen,Eirini Katodritou,Wee‐Joo Chng,Xavier Leleu,Shinsuke Iida,María‐Victoria Mateos,Gareth J. Morgan,Alexander Vorog,Richard Labotka,Bingxia Wang,Antônio Palumbo,Sagar Lonial
摘要
Maintenance therapy prolongs progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM) not undergoing autologous stem cell transplantation (ASCT) but has generally been limited to immunomodulatory agents. Other options that complement the induction regimen with favorable toxicity are needed.The phase III, double-blind, placebo-controlled TOURMALINE-MM4 study randomly assigned (3:2) patients with NDMM not undergoing ASCT who achieved better than or equal to partial response after 6-12 months of standard induction therapy to receive the oral proteasome inhibitor (PI) ixazomib or placebo on days 1, 8, and 15 of 28-day cycles as maintenance for 24 months. The primary endpoint was PFS since time of randomization.Patients were randomly assigned to receive ixazomib (n = 425) or placebo (n = 281). TOURMALINE-MM4 met its primary endpoint with a 34.1% reduction in risk of progression or death with ixazomib versus placebo (median PFS since randomization, 17.4 v 9.4 months; hazard ratio [HR], 0.659; 95% CI, 0.542 to 0.801; P < .001; median follow-up, 21.1 months). Ixazomib significantly benefitted patients who achieved complete or very good partial response postinduction (median PFS, 25.6 v 12.9 months; HR, 0.586; P < .001). With ixazomib versus placebo, 36.6% versus 23.2% of patients had grade ≥ 3 treatment-emergent adverse events (TEAEs); 12.9% versus 8.0% discontinued treatment because of TEAEs. Common any-grade TEAEs included nausea (26.8% v 8.0%), vomiting (24.2% v 4.3%), and diarrhea (23.2% v 12.3%). There was no increase in new primary malignancies (5.2% v 6.2%); rates of on-study deaths were 2.6% versus 2.2%.Ixazomib maintenance prolongs PFS with no unexpected toxicity in patients with NDMM not undergoing ASCT. To our knowledge, this is the first PI demonstrated in a randomized clinical trial to have single-agent efficacy for maintenance and is the first oral PI option in this patient population.
科研通智能强力驱动
Strongly Powered by AbleSci AI