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.

尽管病例对照分析表明克拉霉素与连续来那度胺和地塞米松 (Rd) 的关联具有附加价值，但尚无 III 期试验证实这些结果。在这项 III 期试验中，286 名不适合进行 ASCT 的 MM 患者接受 Rd 联合或不联合克拉霉素直至疾病进展或出现不可接受的毒性。主要终点是无进展生存期（PFS）。中位随访时间为 19 个月（范围 0-54），尽管两组之间的中位 PFS 没有显着差异（C-Rd 23 个月，Rd 29 个月；HR 0.783，p  = 0.14），尽管C-Rd 组的完全缓解率 (CR) 或更好（22.6% vs 14.4%，p = 0.048）。最常见的 G3-4 级不良事件是中性粒细胞减少症 [12% vs 19%] 和感染 [30% vs 25%]，两组相似；然而，C-Rd 组中毒性死亡的百分比更高（36/50 [72%] vs 22/40 [55%]，p = 0.09)。尽管由于 C-Rd 组中毒性死亡人数增加，≥CR 率增加，但在未经治疗的移植不合格 MM 患者中向 Rd 添加克拉霉素并未改善 PFS。由于克拉霉素在该老年人群中引起的延迟清除，与过度暴露于类固醇相关的副作用可以解释这些结果。该试验在clinicaltrials.gov上注册，名称为GEM-CLARIDEX：Ld vs BiRd，标识符为NCT02575144。完整的试验方案可从 ClinicalTrials.gov 访问。这项研究得到了 BMS/Celgene 的资金支持。