University Hospital of Salamanca/IBSAL/CIC, Salamanca, Spain.
University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
Leukemia. 2022 May;36(5):1371-1376. doi: 10.1038/s41375-022-01531-2. Epub 2022 Mar 24.
Despite treatment advances, patients with multiple myeloma (MM) often progress through standard drug classes including proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), and anti-CD38 monoclonal antibodies (mAbs). LocoMMotion (ClinicalTrials.gov identifier: NCT04035226) is the first prospective study of real-life standard of care (SOC) in triple-class exposed (received at least a PI, IMiD, and anti-CD38 mAb) patients with relapsed/refractory MM (RRMM). Patients (N = 248; ECOG performance status of 0-1, ≥3 prior lines of therapy or double refractory to a PI and IMiD) were treated with median 4.0 (range, 1-20) cycles of SOC therapy. Overall response rate was 29.8% (95% CI: 24.2-36.0). Median progression-free survival (PFS) and median overall survival (OS) were 4.6 (95% CI: 3.9-5.6) and 12.4 months (95% CI: 10.3-NE). Treatment-emergent adverse events (TEAEs) were reported in 83.5% of patients (52.8% grade 3/4). Altogether, 107 deaths occurred, due to progressive disease (n = 74), TEAEs (n = 19), and other reasons (n = 14). The 92 varied regimens utilized demonstrate a lack of clear SOC for heavily pretreated, triple-class exposed patients with RRMM in real-world practice and result in poor outcomes. This supports a need for new treatments with novel mechanisms of action.
尽管治疗取得了进展,但多发性骨髓瘤(MM)患者通常会通过标准药物类别进展,包括蛋白酶体抑制剂(PIs)、免疫调节剂(IMiDs)和抗 CD38 单克隆抗体(mAbs)。LocoMMotion(ClinicalTrials.gov 标识符:NCT04035226)是首个针对三药暴露(至少接受过一种 PI、IMiD 和抗 CD38 mAb)复发/难治性 MM(RRMM)患者的真实标准治疗(SOC)的前瞻性研究。患者(N=248;ECOG 表现状态为 0-1,≥3 线既往治疗或对 PI 和 IMiD 双重耐药)接受 SOC 治疗中位数为 4.0 个周期(范围,1-20)。总缓解率为 29.8%(95%CI:24.2-36.0)。中位无进展生存期(PFS)和中位总生存期(OS)分别为 4.6(95%CI:3.9-5.6)和 12.4 个月(95%CI:10.3-NE)。83.5%的患者发生了治疗相关不良事件(TEAEs)(52.8%为 3/4 级)。共有 107 例死亡,原因分别为疾病进展(n=74)、TEAEs(n=19)和其他原因(n=14)。在真实世界实践中,92 种不同的方案用于治疗三药暴露、大量预处理的 RRMM 患者,结果显示 SOC 方案缺乏明确性,导致治疗结局不佳。这支持了需要开发具有新型作用机制的新疗法。