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硼替佐米和来那度胺(VR)联合无地塞米松巩固治疗多发性骨髓瘤患者移植后:无双膦酸盐情况下对生存和骨骼结局的影响。

Consolidation therapy with the combination of bortezomib and lenalidomide (VR) without dexamethasone in multiple myeloma patients after transplant: Effects on survival and bone outcomes in the absence of bisphosphonates.

机构信息

Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece.

Department of Hematology, 251 General Air-Force Hospital, Athens, Greece.

出版信息

Am J Hematol. 2019 Apr;94(4):400-407. doi: 10.1002/ajh.25392. Epub 2019 Jan 10.

Abstract

Optimizing consolidation treatment in transplant-eligible newly diagnosed multiple myeloma patients in order to improve efficacy and bone-related outcomes is intriguing. We conducted an open-label, prospective study evaluating the efficacy and safety of bortezomib and lenalidomide (VR) consolidation after ASCT, in the absence of dexamethasone and bisphosphonates. Fifty-nine patients, who received bortezomib-based induction, were given 4 cycles of VR starting on day 100 post-ASCT. After ASCT, 58% of patients improved their response status, while following VR consolidation 39% further deepened their response; stringent complete response rates increased to 51% after VR from 24% post-ASCT. VR consolidation resulted in a significant reduction of soluble receptor activator of nuclear factor-κB ligand/osteoprotegerin ratio and sclerostin circulating levels, which was more pronounced among patients achieving very good partial response or better. After a median follow-up of 62 months, no skeletal-related events (SREs) were observed, despite the lack of bisphosphonates administration. The median TTP after ASCT was 37 months, while median overall survival (OS) has not been reached yet; the probability of 4- and 5-year OS was 81% and 64%, respectively. In conclusion, VR consolidation is an effective, dexamethasone- and bisphosphonate-free approach, which offers long OS with improvements on bone metabolism and no SREs.

摘要

优化适合移植的初诊多发性骨髓瘤患者的巩固治疗,以提高疗效和改善与骨骼相关的结局,这是很有吸引力的。我们进行了一项开放性、前瞻性研究,评估了硼替佐米和来那度胺(VR)巩固治疗在没有地塞米松和双膦酸盐的情况下,在 ASCT 后的疗效和安全性。59 例接受硼替佐米为基础的诱导治疗的患者,在 ASCT 后第 100 天开始接受 4 个周期的 VR。ASCT 后,58%的患者改善了缓解状态,而在接受 VR 巩固治疗后,39%的患者进一步加深了缓解程度;严格的完全缓解率从 ASCT 后的 24%增加到 VR 后的 51%。VR 巩固治疗导致可溶性核因子-κB 配体/骨保护素受体比率和硬化素循环水平显著降低,在达到非常好的部分缓解或更好的患者中更为明显。在中位随访 62 个月后,尽管未使用双膦酸盐,但未观察到骨骼相关事件(SREs)。ASCT 后的中位无进展生存期(TTP)为 37 个月,而中位总生存期(OS)尚未达到;4 年和 5 年 OS 的概率分别为 81%和 64%。总之,VR 巩固治疗是一种有效、无地塞米松和双膦酸盐的方法,可提供长期的 OS,改善骨代谢,且无 SREs。

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