Hematology Department, Mianyang Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No 12. Changjia Alley, Jingzhong Street, Fucheng District, Mianyang, 621000, China.
Clin Exp Med. 2023 Sep;23(5):1573-1580. doi: 10.1007/s10238-022-00879-0. Epub 2022 Sep 12.
The aim of this study is to analyze the efficacy and safety of sequential therapy with bortezomib-based triplet regimens without lenalidomide (PXD, including VTD, PAD, and VCD) followed by continuous lenalidomide and dexamethasone (Rd) or bortezomib and dexamethasone (Vd) treatment. The main objective is to evaluate the advantages of PXD followed by Rd compared to the combinations of bortezomib-lenalidomide-dexamethasone (VRd) in newly diagnosed multiple myeloma (NDMM). Fifty-eight nontransplant NDMM patients who were admitted to our department from 2017 to 2019 were included in this study. Bortezomib-based triplet regimens were initially selected and followed by Rd or Vd as continuous treatment once the patients achieved partial remission (PR) or better response. The efficacy and safety of the patients were observed. The Rd continuous treatment cohort was compared with historical data from the EVOLUTION trial on continuous VRd treatment. In our cohort, the overall survival rate was 100%, and progression-free survival (PFS) was 38.5% after a median of 19 (4-36) cycles of Rd continuous therapy was applied. During the follow-up period, the best outcome assessments achieved were 53.8% complete response (CR) and 84.6% excellent partial response (VGPR). A total of 23.1% had grade 3-4 or higher drug-related adverse reactions, mainly hematological toxicity, and no patients died of adverse reactions. Compared with the Vd group, the Rd group had a better PFS and VGPR rate (2-year PFS: 92.3% vs. 56.3%, P = 0.002; 3-year PFS: 69.2% vs. 8.0%, P < 0.001; VGPR: 84.6% vs. 69.2%, P = 0.02). No significant differences were found in ORR (100% vs. 92.3%) or CR (53.8% vs. 35.7%, P = 0.082). Compared with the EVOLUTION study, patients in the Rd group had a more advanced disease stage (stage III rate of 40% vs. 19%, P = 0.039) and worse physical status (KPS 50-60 rate of 25.0% vs. 2.0%, P = 0.000). However, a higher proportion of ORR (100% vs. 73.0%, P < 0.001), VGPR or better (75.0% vs. 32.0%, P < 0.001), and PFS at 12 months (90.0% vs. 68%, P = 0.011) were achieved. Sequential administration of bortezomib-based triplet regimens without lenalidomide as an initial therapy followed by Rd as a continuous treatment may not be inferior to VRd for first-line treatment in NDMM patients.
本研究旨在分析不使用来那度胺的硼替佐米三联方案(PXD,包括 VTD、PAD 和 VCD)序贯治疗后,连续应用来那度胺和地塞米松(Rd)或硼替佐米和地塞米松(Vd)治疗的疗效和安全性。主要目的是评估 PXD 序贯 Rd 治疗与新诊断多发性骨髓瘤(NDMM)中硼替佐米-来那度胺-地塞米松(VRd)联合治疗相比的优势。本研究纳入了 2017 年至 2019 年期间在我科就诊的 58 例非移植 NDMM 患者。患者初始选择硼替佐米三联方案,达到部分缓解(PR)或更好反应后,再应用 Rd 或 Vd 作为连续治疗。观察患者的疗效和安全性。将 Rd 连续治疗组与 EVOLUTION 试验中 VRd 连续治疗的历史数据进行比较。在本队列中,Rd 连续治疗 19(4-36)个周期后,患者的总生存率为 100%,无进展生存率(PFS)为 38.5%。在随访期间,最佳疗效评估结果为 53.8%完全缓解(CR)和 84.6%非常好的部分缓解(VGPR)。共发生 23.1%的 3-4 级或更高的药物相关不良反应,主要为血液学毒性,无患者因不良反应死亡。与 Vd 组相比,Rd 组的 PFS 和 VGPR 率更好(2 年 PFS:92.3%比 56.3%,P=0.002;3 年 PFS:69.2%比 8.0%,P<0.001;VGPR:84.6%比 69.2%,P=0.02)。两组患者的总缓解率(100%比 92.3%)或 CR(53.8%比 35.7%,P=0.082)无显著差异。与 EVOLUTION 研究相比,Rd 组患者的疾病分期更晚(III 期比例为 40%比 19%,P=0.039),一般状况更差(KPS 50-60 比例为 25.0%比 2.0%,P=0.000)。然而,Rd 组患者的总缓解率(100%比 73.0%,P<0.001)、VGPR 或更好(75.0%比 32.0%,P<0.001)和 12 个月时的 PFS(90.0%比 68%,P=0.011)更高。不使用来那度胺的硼替佐米三联方案作为初始治疗序贯治疗,然后用 Rd 作为连续治疗,可能与 VRd 一线治疗 NDMM 患者疗效相当。