Moreau Philippe, Hulin Cyrille, Zweegman Sonja, Hashim Mahmoud, Hu Yannan, Heeg Bart, de Boer Carla, Vanquickelberghe Veronique, Kampfenkel Tobias, He Jianming, Lam Annette, Cote Sarah, Sonneveld Pieter
Nantes University Hospital Hôtel-Dieu Nantes France.
Hospital Center University De Bordeaux Bordeaux France.
EJHaem. 2020 Nov 7;2(1):66-80. doi: 10.1002/jha2.129. eCollection 2021 Feb.
Traditional bortezomib, thalidomide, and dexamethasone (VTd) regimens for patients with newly diagnosed multiple myeloma (NDMM) include doses of thalidomide up to 200 mg/day (VTd-label). Clinical practice has evolved to use a lower dose (100 mg/day) to reduce toxicity (VTd-mod), which was evaluated in the phase III CASSIOPEIA study, without or with daratumumab (D-VTd; an anti-CD38 monoclonal antibody). We used propensity score matching to compare efficacy and safety for VTd-mod and D-VTd with VTd-label.
Patient-level data for VTd-mod and D-VTd from CASSIOPEIA (NCT02541383) and data for VTd-label from the PETHEMA/GEM study (NCT00461747) were analyzed. Propensity scores were estimated using logistic regression, and nearest-neighbor matching procedure was used. Outcomes included overall survival (OS), progression-free survival (PFS), time to progression (TTP), postinduction and posttransplant responses, as well as rate of treatment discontinuation and grade 3/4 peripheral neuropathy.
VTd-mod was noninferior to VTd-label for OS, PFS, TTP, postinduction very good partial response or better (≥VGPR) and overall response rate (ORR). VTd-mod was significantly better for posttransplant ≥VGPR and ORR versus VTd-label. VTd-mod safety was not superior to VTd-label despite the lower thalidomide dose. D-VTd was significantly better than VTd-label for OS, PFS, TTP, postinduction and posttransplant ≥VGPR and ORR, and was noninferior to VTd-label for safety outcomes.
In transplant-eligible patients with NDMM, D-VTd had superior efficacy compared with VTd-label. Despite a lower dose of thalidomide, VTd-mod was noninferior to VTd-label for safety and was significantly better for posttransplant ≥VGPR/ORR. These data further support the first-line use of daratumumab plus VTd.
用于新诊断的多发性骨髓瘤（NDMM）患者的传统硼替佐米、沙利度胺和地塞米松（VTd）方案包括高达200毫克/天的沙利度胺剂量（VTd标准方案）。临床实践已发展为使用较低剂量（100毫克/天）以降低毒性（VTd改良方案），该方案在III期CASSIOPEIA研究中进行了评估，该研究纳入或未纳入达雷妥尤单抗（D-VTd；一种抗CD38单克隆抗体）。我们使用倾向评分匹配法比较VTd改良方案和D-VTd方案与VTd标准方案的疗效和安全性。
分析了来自CASSIOPEIA（NCT02541383）的VTd改良方案和D-VTd方案的患者水平数据以及来自PETHEMA/GEM研究（NCT00461747）的VTd标准方案数据。使用逻辑回归估计倾向评分，并采用最近邻匹配程序。结局包括总生存期（OS）、无进展生存期（PFS）、疾病进展时间（TTP）、诱导后和移植后反应，以及治疗中断率和3/4级周围神经病变。
在OS、PFS、TTP、诱导后非常好的部分缓解或更好（≥VGPR）以及总缓解率（ORR）方面，VTd改良方案不劣于VTd标准方案。在移植后≥VGPR和ORR方面，VTd改良方案显著优于VTd标准方案。尽管沙利度胺剂量较低，但VTd改良方案的安全性并不优于VTd标准方案。在OS、PFS、TTP、诱导后和移植后≥VGPR和ORR方面，D-VTd方案显著优于VTd标准方案，在安全性结局方面不劣于VTd标准方案。
在适合移植的NDMM患者中，D-VTd方案与VTd标准方案相比具有更高的疗效。尽管沙利度胺剂量较低，但VTd改良方案在安全性方面不劣于VTd标准方案，且在移植后≥VGPR/ORR方面显著更好。这些数据进一步支持一线使用达雷妥尤单抗联合VTd方案。
