文章：

来那度胺联合地塞米松，加或不加克拉霉素，用于不适合自体移植的多发性骨髓瘤患者：一项随机试验

Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial

原文发布日期：2021-05-21

DOI: 10.1038/s41408-021-00490-8

类型: Article

开放获取: 是

英文摘要：

Although case-control analyses have suggested an additive value with the association of clarithromycin to continuous lenalidomide and dexamethasone (Rd), there are not phase III trials confirming these results. In this phase III trial, 286 patients with MM ineligible for ASCT received Rd with or without clarithromycin until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival (PFS). With a median follow-up of 19 months (range, 0–54), no significant differences in the median PFS were observed between the two arms (C-Rd 23 months, Rd 29 months; HR 0.783, p = 0.14), despite a higher rate of complete response (CR) or better in the C-Rd group (22.6% vs 14.4%, p = 0.048). The most common G3–4 adverse events were neutropenia [12% vs 19%] and infections [30% vs 25%], similar between the two arms; however, the percentage of toxic deaths was higher in the C-Rd group (36/50 [72%] vs 22/40 [55%], p = 0.09). The addition of clarithromycin to Rd in untreated transplant ineligible MM patients does not improve PFS despite increasing the ≥CR rate due to the higher number of toxic deaths in the C-Rd arm. Side effects related to overexposure to steroids due to its delayed clearance induced by clarithromycin in this elderly population could explain these results. The trial was registered in clinicaltrials.gov with the name GEM-CLARIDEX: Ld vs BiRd and with the following identifier NCT02575144. The full trial protocol can be accessed from ClinicalTrials.gov. This study received financial support from BMS/Celgene.
 

摘要翻译： 

虽然病例对照分析提示克拉霉素联合连续来那度胺和地塞米松方案具有叠加价值，但目前尚无III期试验证实这些结果。在这项III期试验中，286名不适合接受自体干细胞移植的多发性骨髓瘤患者被随机分配接受Rd方案联合或不联合克拉霉素治疗，直至疾病进展或出现不可耐受的毒性。主要终点是无进展生存期。中位随访19个月（范围0-54个月）后，尽管C-Rd组的完全缓解或更好缓解率更高，但两组的中位无进展生存期无显著差异。两组最常见的3-4级不良事件相似，但C-Rd组的毒性死亡比例更高。对于未经治疗且不适合移植的多发性骨髓瘤患者，在Rd方案中添加克拉霉素虽可提高完全缓解率，但由于C-Rd组毒性死亡增加，并未改善无进展生存期。这些结果可能与该老年群体中克拉霉素导致类固醇清除延迟从而引发药物过量相关的副作用有关。该试验已注册于临床研究网站，研究方案可在该网站获取。本研究获得了百时美施贵宝/新基公司的资金支持。

原文链接：

Lenalidomide and dexamethasone with or without clarithromycin in patients with multiple myeloma ineligible for autologous transplant: a randomized trial