1 University of Pennsylvania, Philadelphia, PA.
2 Medical College of Wisconsin, Milwaukee, WI.
J Clin Oncol. 2019 Mar 1;37(7):589-597. doi: 10.1200/JCO.18.00685. Epub 2019 Jan 17.
Single-cycle melphalan 200 mg/m and autologous hematopoietic cell transplantation (AHCT) followed by lenalidomide (len) maintenance have improved progression-free survival (PFS) and overall survival (OS) for transplantation-eligible patients with multiple myeloma (MM). We designed a prospective, randomized, phase III study to test additional interventions to improve PFS by comparing AHCT, tandem AHCT (AHCT/AHCT), and AHCT and four subsequent cycles of len, bortezomib, and dexamethasone (RVD; AHCT + RVD), all followed by len until disease progression.
Patients with symptomatic MM within 12 months from starting therapy and without progression who were age 70 years or younger were randomly assigned to AHCT/AHCT + len (n = 247), AHCT + RVD + len (n = 254), or AHCT + len (n = 257). The primary end point was 38-month PFS.
The study population had a median age of 56 years (range, 20 to 70 years); 24% of patients had high-risk MM, 73% had a triple-drug regimen as initial therapy, and 18% were in complete response at enrollment. The 38-month PFS rate was 58.5% (95% CI, 51.7% to 64.6%) for AHCT/AHCT + len, 57.8% (95% CI, 51.4% to 63.7%) for AHCT + RVD + len, and 53.9% (95% CI, 47.4% to 60%) for AHCT + len. For AHCT/AHCT + len, AHCT + RVD + len, and AHCT + len, the OS rates were 81.8% (95% CI, 76.2% to 86.2%), 85.4% (95% CI, 80.4% to 89.3%), and 83.7% (95% CI, 78.4% to 87.8%), respectively, and the complete response rates at 1 year were 50.5% (n = 192), 58.4% (n = 209), and 47.1% (n = 208), respectively. Toxicity profiles and development of second primary malignancies were similar across treatment arms.
Second AHCT or RVD consolidation as post-AHCT interventions for the up-front treatment of transplantation-eligible patients with MM did not improve PFS or OS. Single AHCT and len should remain as the standard approach for this population.
单周期美法仑 200mg/m2 和自体造血细胞移植（AHCT）后接受来那度胺（len）维持治疗，可改善适合移植的多发性骨髓瘤（MM）患者的无进展生存期（PFS）和总生存期（OS）。我们设计了一项前瞻性、随机、III 期研究，通过比较 AHCT、串联 AHCT（AHCT/AHCT）和 AHCT 以及随后的 4 个周期来那度胺、硼替佐米和地塞米松（RVD；AHCT+RVD），来测试额外干预措施以改善 PFS，所有这些治疗后均接受 len 治疗，直至疾病进展。
在开始治疗后 12 个月内出现症状且无进展的 70 岁以下有症状 MM 患者被随机分配至 AHCT/AHCT+len（n=247）、AHCT+RVD+len（n=254）或 AHCT+len（n=257）组。主要终点为 38 个月 PFS。
研究人群的中位年龄为 56 岁（范围 20 至 70 岁）；24%的患者具有高危 MM，73%的患者初始治疗采用三药方案，18%的患者在入组时达到完全缓解。AHCT/AHCT+len、AHCT+RVD+len 和 AHCT+len 的 38 个月 PFS 率分别为 58.5%（95%CI，51.7%至 64.6%）、57.8%（95%CI，51.4%至 63.7%）和 53.9%（95%CI，47.4%至 60%）。AHCT/AHCT+len、AHCT+RVD+len 和 AHCT+len 的 OS 率分别为 81.8%（95%CI，76.2%至 86.2%）、85.4%（95%CI，80.4%至 89.3%）和 83.7%（95%CI，78.4%至 87.8%），1 年完全缓解率分别为 50.5%（n=192）、58.4%（n=209）和 47.1%（n=208）。各治疗组的毒性谱和第二原发性恶性肿瘤的发生情况相似。
在适合移植的 MM 患者的一线治疗中，作为 AHCT 后干预的二次 AHCT 或 RVD 巩固治疗并未改善 PFS 或 OS。单次 AHCT 和 len 仍应作为该人群的标准治疗方法。
