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硼替佐米、沙利度胺和地塞米松与硼替佐米、地塞米松诱导治疗用于拉丁美洲国家适合移植的多发性骨髓瘤患者的真实世界结局:来自阿根廷多发性骨髓瘤组的回顾性队列研究。

Real world outcomes with Bortezomib Thalidomide dexamethasone and Cyclophosphamide Bortezomib dexamethasone induction treatment for transplant eligible multiple myeloma patients in a Latin American country. A Retrospective Cohort Study from Grupo Argentino de Mieloma Múltiple.

机构信息

Hospital Italiano de Buenos Aires - Servicio de Clínica Médica (Sección Hematología), Buenos Aires, Argentina.

Instituto Alexander Fleming - Departamento de Hematología, Buenos Aires, Argentina.

出版信息

Hematol Oncol. 2020 Aug;38(3):363-371. doi: 10.1002/hon.2729. Epub 2020 Apr 20.

Abstract

Data about treatment outcomes and toxicity in Latin America are scarce. There are differences with central countries based on access to healthcare system and socioeconomic status. Argentinean Society of Hematology recommends bortezomib-based triplets for induction treatment of transplant eligible newly diagnosed multiple myeloma patients. Most common options are CyBorD (cyclophosphamide, bortezomib and dexamethasone) and VTD (bortezomib, thalidomide and dexamethasone). Main goal of our retrospective, multicentric study was to compare very good partial response rate (VGPR) or better after induction treatment in a real-world setting in Argentina. Secondary objectives included comparison of complete response (CR) post-induction and after bone marrow transplantation, grade 3-4 adverse events (AEs), progression-free survival (PFS) and overall survival (OS). Three hundred twenty-two patients were included (median age at diagnosis: 57 years; 52% male; 28% had ISS3; 14% with high-risk cytogenetics; median follow up: 34 months). CyBorD was indicated in 74% and 26% received VTD. In VTD arm, 72.62% of patients achieved at least VGPR vs 53.36% receiving CyBorD (odds ratio, OR: 1.96 [95% confidence interval, CI: 1.08-3.57; P = .026] after adjusting by age, ISS [International Staging System], lactate dehydrogenase levels (LDH) and cytogenetic risk. Difference in VGPR was 19.26% (95% CI: 15-24). CR rate were 35.92% (VTD) vs 22.55% (CyBorD) (adjusted OR: 2.13 [95% CI: 1.12-4.05]). Difference in CR was 13.37% (95% CI: 9.6-17.53). Adverse events (AEs) were more common with VTD (69.05% vs 55.46% for CyBorD; P = .030), especially grade 3-4 neuropathy (P = .005) and thrombosis (P = .001). Thromboprophylaxis was inadequate in 20.24% of patients. Hematological AEs were more common with CyBorD, especially thrombocytopenia (P = .017). PFS and OS at 24 months were not different between treatments. In this real-world setting, VTD was associated with better CR and VGPR than CyBorD. Nevertheless, CyBorD continues to be the preferred induction regimen in Argentina, based on safety profile. Frontline autologous stem cell transplantation improves quality of responses, especially in countries with limited access to new drugs.

摘要

关于拉丁美洲的治疗结果和毒性的数据很少。由于获得医疗保健系统和社会经济地位的差异,与中心国家存在差异。阿根廷血液学学会建议为符合移植条件的新诊断多发性骨髓瘤患者推荐硼替佐米为基础的三联方案进行诱导治疗。最常见的选择是 CyBorD(环磷酰胺、硼替佐米和地塞米松)和 VTD(硼替佐米、沙利度胺和地塞米松)。我们回顾性、多中心研究的主要目的是比较阿根廷真实世界环境中诱导治疗后的非常好的部分缓解率(VGPR)或更好。次要目标包括比较诱导后和骨髓移植后的完全缓解(CR)、3-4 级不良事件(AE)、无进展生存期(PFS)和总生存期(OS)。共纳入 322 例患者(中位诊断年龄:57 岁;52%为男性;28%为 ISS3;14%具有高危细胞遗传学;中位随访:34 个月)。74%的患者使用 CyBorD,26%的患者使用 VTD。在 VTD 组中,72.62%的患者至少达到 VGPR,而接受 CyBorD 的患者为 53.36%(调整年龄、ISS(国际分期系统)、乳酸脱氢酶(LDH)和细胞遗传学风险后,比值比为 1.96[95%置信区间:1.08-3.57;P=.026])。VGPR 差异为 19.26%(95%置信区间:15-24)。CR 率为 35.92%(VTD)与 22.55%(CyBorD)(调整比值比为 2.13[95%置信区间:1.12-4.05])。CR 差异为 13.37%(95%置信区间:9.6-17.53)。VTD 的不良事件(AE)更为常见(69.05% vs 55.46% CyBorD;P=.030),尤其是 3-4 级神经病变(P=.005)和血栓形成(P=.001)。20.24%的患者未进行充分的血栓预防。CyBorD 引起的血液学 AE 更为常见,尤其是血小板减少症(P=.017)。24 个月时的 PFS 和 OS 在两种治疗方法之间没有差异。在这种真实环境下,与 CyBorD 相比,VTD 与更好的 CR 和 VGPR 相关。然而,基于安全性特征,CyBorD 仍然是阿根廷首选的诱导方案。一线自体干细胞移植可改善反应质量,尤其是在新药获取有限的国家。

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