Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.
Department of Cancer Prevention, Silesian Medical University, Katowice, Poland.
Eur J Cancer. 2019 Jan;106:89-98. doi: 10.1016/j.ejca.2018.09.011. Epub 2018 Nov 22.
Novel efficacious treatments with long-term tolerability are needed for transplant-ineligible, newly diagnosed multiple myeloma (NDMM) patients. This phase 2 study evaluated the safety and efficacy of all-oral ixazomib-cyclophosphamide-dexamethasone (ICd) followed by single-agent ixazomib maintenance.
Patients were randomised (1:1) to receive 4.0 mg of ixazomib, 300 (Arm A) or 400 (Arm B) mg/m of cyclophosphamide (days 1, 8, and 15), and 40 mg of dexamethasone (days 1, 8, 15, and 22) as induction (up to 13 × 28-day cycles), followed by single-agent ixazomib maintenance (28-day cycles) until progressive disease, death, or unacceptable toxicity. Primary end-point was complete response (CR) + very good partial response (VGPR) rate for ICd induction.
Seventy patients were enrolled (n = 36 Arm A; n = 34 Arm B); median age was 73 years (range, 61-87). At data cut-off, 66% of patients had completed 13 induction cycles followed by ixazomib maintenance. Median overall treatment duration was 19 cycles (range, 1-29); 21% of patients discontinued treatment during induction and 3% during maintenance due to adverse events (AEs). During induction, among 67 response-evaluable patients, CR+VGPR rate was 25%, and overall response rate (ORR) was 73%. Including the maintenance phase, CR+VGPR rate was 33%, and ORR was 76%. Median progression-free survival was 23.5 months (median follow-up: 26.1 months). The most common all-grade AE was neutropenia (31%). Grade ≥3 AEs were reported by 73% of patients. Five on-study deaths occurred (not treatment-related).
ICd treatment followed by ixazomib maintenance is tolerable and active in elderly, transplant-ineligible NDMM patients.
NCT02046070.
对于不适合移植的新诊断多发性骨髓瘤（NDMM）患者，需要具有长期耐受性的新型有效治疗方法。这项 2 期研究评估了全口服伊沙佐米联合环磷酰胺和地塞米松（ICd）治疗后，再用伊沙佐米单药维持治疗的安全性和疗效。
患者按 1:1 随机分组，分别接受 4.0mg 伊沙佐米、300mg（A 组）或 400mg（B 组）环磷酰胺（第 1、8 和 15 天）和 40mg 地塞米松（第 1、8、15 和 22 天）诱导治疗（最多 13 个 28 天周期），然后接受伊沙佐米单药维持治疗（28 天周期），直至疾病进展、死亡或不可接受的毒性。主要终点为 ICd 诱导的完全缓解（CR）+非常好的部分缓解（VGPR）率。
70 例患者入组（n=36 例 A 组；n=34 例 B 组）；中位年龄为 73 岁（范围，61-87 岁）。数据截止时，66%的患者已完成 13 个诱导周期，随后接受伊沙佐米维持治疗。中位总治疗时间为 19 个周期（范围，1-29 个）；21%的患者因不良事件（AE）在诱导期停药，3%的患者在维持期停药。在诱导期，67 例可评价疗效的患者中，CR+VGPR 率为 25%，总缓解率（ORR）为 73%。包括维持期，CR+VGPR 率为 33%，ORR 为 76%。中位无进展生存期为 23.5 个月（中位随访时间：26.1 个月）。最常见的所有级别 AE 是中性粒细胞减少症（31%）。73%的患者发生了≥3 级的 AE。5 例患者发生了研究相关死亡。
在不适合移植的新诊断多发性骨髓瘤患者中，ICd 治疗后用伊沙佐米维持治疗是耐受的且有效的。
NCT02046070。
