Combination treatment regimens including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and a corticosteroid are standards of care for initial treatment of multiple myeloma (MM). We aimed to evaluate if a sequential treatment program using PI induction followed by IMiD based consolidation and maintenance could achieve similar outcomes with reduced toxicities. This phase 2 study was designed to assess the safety and efficacy of the Car-BiRd regimen: carfilzomib and dexamethasone (Kd) induction until maximum response, followed by lenalidomide, clarithromycin and dexamethasone (BiRd) consolidation until next maximum response, then lenalidomide maintenance in patients with newly diagnosed MM. Seventy-two patients, including both transplant eligible and ineligible patients, were enrolled and evaluated for response. The overall response rate to the Car-BiRd regimen was 94% with 83% of patients achieving a ≥ VGPR and 35% achieving a CR/sCR. The rate of CR/sCR increased from 7% with Kd induction to 21% with BiRd consolidation and 35% with lenalidomide maintenance. These results did not meet the study's target endpoint of a CR rate of 55%. The median PFS using this deferred transplant approach was 37.3 months (95% CI 27.9, 52.7) and median OS was not reached with a median follow-up of 60 months. Toxicities were primarily low grade and manageable. Hematologic toxicities were lower than those expected with a combination PI/IMiD protocol. The sequential Car-BiRd regimen is an effective and safe approach for the upfront treatment of MM including patients unfit for transplant.

中文翻译：

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卡非佐米和地塞米松联合来那度胺、克拉霉素和地塞米松巩固治疗和来那度胺维持治疗新诊断的多发性骨髓瘤

包括蛋白酶体抑制剂 (PI)、免疫调节剂 (IMiD) 和皮质类固醇在内的联合治疗方案是多发性骨髓瘤 (MM) 初始治疗的护理标准。我们旨在评估使用 PI 诱导继以基于 IMiD 的巩固和维持的序贯治疗计划是否可以在降低毒性的情况下实现类似的结果。这项 2 期研究旨在评估 Car-BiRd 方案的安全性和有效性：卡非佐米和地塞米松 (Kd) 诱导直至最大反应，然后是来那度胺、克拉霉素和地塞米松 (BiRd) 巩固直至下一个最大反应，然后是来那度胺维持治疗新诊断的MM患者。包括符合移植条件和不符合移植条件的患者在内的 72 名患者被纳入并评估了反应。Car-BiRd 方案的总体反应率为 94%，83% 的患者达到 ≥ VGPR，35% 的患者达到 CR/sCR。CR/sCR 率从 Kd 诱导的 7% 增加到 BiRd 巩固的 21% 和来那度胺维持的 35%。这些结果没有达到研究的 55% CR 率的目标终点。使用这种延迟移植方法的中位 PFS 为 37.3 个月（95% CI 27.9, 52.7），中位 OS 未达到中位随访 60 个月。毒性主要是低级和可控的。血液学毒性低于联合 PI/IMiD 方案的预期。序贯 Car-BiRd 方案是一种有效且安全的方法，可用于 MM 的前期治疗，包括不适合移植的患者。