Myeloma Unit, Division of Hematology, University of Torino, Azienda Ospedaliero-Universitaria Città della Salute e della Scienza di Torino, Torino, Italy.
Division of Hematology, Department of Translational Medicine, University of Eastern Piedmont, Novara, Italy.
Blood. 2021 Jun 3;137(22):3027-3036. doi: 10.1182/blood.2020009507.
Lenalidomide-dexamethasone (Rd) is standard treatment for elderly patients with multiple myeloma (MM). In this randomized phase 3 study, we investigated efficacy and feasibility of dose/schedule-adjusted Rd followed by maintenance at 10 mg per day without dexamethasone (Rd-R) vs continuous Rd in elderly, intermediate-fit newly diagnosed patients with MM. Primary end point was event-free survival (EFS), defined as progression/death from any cause, lenalidomide discontinuation, or hematologic grade 4 or nonhematologic grade 3 to 4 adverse event (AE). Of 199 evaluable patients, 101 received Rd-R and 98 continuous Rd. Median follow-up was 37 months. EFS was 10.4 vs 6.9 months (hazard ratio [HR], 0.70; 95% confidence interval [CI], 0.51-0.95; P = .02); median progression-free survival, 20.2 vs 18.3 months (HR, 0.78; 95% CI, 0.55-1.10; P = .16); and 3-year overall survival, 74% vs 63% (HR, 0.62; 95% CI, 0.37-1.03; P = .06) with Rd-R vs Rd, respectively. Rate of ≥1 nonhematologic grade ≥3 AE was 33% vs 43% (P = .14) in Rd-R vs Rd groups, with neutropenia (21% vs 18%), infections (10% vs 12%), and skin disorders (7% vs 3%) the most frequent; constitutional and central nervous system AEs mainly related to dexamethasone were more frequent with Rd. Lenalidomide was discontinued for AEs in 24% vs 30% and reduced in 45% vs 62% of patients receiving Rd-R vs Rd, respectively. In intermediate-fit patients, switching to reduced-dose lenalidomide maintenance without dexamethasone after 9 Rd cycles was feasible, with similar outcomes to standard continuous Rd. This trial was registered at www.clinicaltrials.gov as #NCT02215980.
来那度胺-地塞米松（Rd）是治疗老年多发性骨髓瘤（MM）患者的标准疗法。在这项随机 3 期研究中，我们研究了剂量/方案调整后的 Rd 随后维持 10 毫克/天而不使用地塞米松（Rd-R）与连续 Rd 在老年、中等体能新发 MM 患者中的疗效和可行性。主要终点是无事件生存（EFS），定义为任何原因的进展/死亡、来那度胺停药、或血液学 4 级或非血液学 3 级至 4 级不良事件（AE）。在 199 例可评估的患者中，101 例接受了 Rd-R，98 例接受了连续 Rd。中位随访时间为 37 个月。EFS 为 10.4 个月 vs 6.9 个月（风险比[HR]，0.70；95%置信区间[CI]，0.51-0.95；P =.02）；中位无进展生存期为 20.2 个月 vs 18.3 个月（HR，0.78；95%CI，0.55-1.10；P =.16）；3 年总生存率为 74% vs 63%（HR，0.62；95%CI，0.37-1.03；P =.06）Rd-R 组分别比 Rd 组。Rd-R 组≥1 例非血液学 3 级及以上 AE 发生率为 33%，Rd 组为 43%（P =.14），其中中性粒细胞减少症（21% vs 18%）、感染（10% vs 12%）和皮肤疾病（7% vs 3%）最为常见；与地塞米松相关的主要与来那度胺有关的躯体和中枢神经系统 AE 更为常见。由于 AE，Rd-R 组中有 24%的患者停止使用来那度胺，45%的患者减少了来那度胺的剂量，而 Rd 组中分别有 30%和 62%的患者停止使用来那度胺。在中等体能患者中，在接受 9 个 Rd 周期后，转换为无地塞米松的低剂量来那度胺维持治疗是可行的，其结果与标准连续 Rd 相似。该试验在 www.clinicaltrials.gov 上注册为 #NCT02215980。
