Treatment of relapsed/refractory multiple myeloma (RRMM) is challenging as patients exhaust all available therapies and the disease becomes refractory to standard drug classes. Here we report the final results of LocoMMotion, the first prospective study of real-world clinical practice (RWCP) in triple-class exposed (TCE) patients with RRMM, with a median follow-up of 26.4 months (range, 0.1–35.0). Patients (N = 248) had received median 4 prior LOT (range, 2–13) at enrollment. 91 unique regimens were used in index LOT. Overall response rate was 31.9% (95% CI, 26.1–38.0), median progression-free survival (PFS) was 4.6 months (95% CI, 3.9–5.6) and median overall survival was 13.8 months (95% CI, 10.8–17.0). 152 patients (61.3%) had subsequent LOTs with 134 unique regimens, of which 78 were used in first subsequent LOT. Median PFS2 (from start of study through first subsequent LOT) was 10.8 months (95% CI, 8.4–13.0). 158 patients died on study, 67.7% due to progressive disease. Additional subgroup analyses and long-term safety summaries are reported. The high number of RWCP treatment regimens utilized and poor clinical outcomes confirm a lack of standardized treatment for TCE patients with RRMM, highlighting the need for new treatments with novel mechanisms.

复发/难治性多发性骨髓瘤 (RRMM) 的治疗具有挑战性，因为患者用尽所有可用的疗法并且该疾病对标准药物类别变得难治。在这里，我们报告 LocoMMotion 的最终结果，这是第一个针对三级暴露 (TCE) RRMM 患者的现实临床实践 (RWCP) 前瞻性研究，中位随访时间为 26.4 个月（范围，0.1-35.0） 。患者 ( N = 248) 在入组时接受过中位数 4 次先前 LOT（范围，2-13）。索引 LOT 中使用了 91 种独特的方案。总体缓解率为 31.9%（95% CI，26.1–38.0），中位无进展生存期 (PFS) 为 4.6 个月（95% CI，3.9–5.6），中位总生存期为 13.8 个月（95% CI，10.8– 17.0）。 152 名患者 (61.3%) 接受了包含 134 种独特方案的后续 LOT，其中 78 种用于首次后续 LOT。中位 PFS2（从研究开始到随后的第一次 LOT）为 10.8 个月（95% CI，8.4-13.0）。研究中有 158 名患者死亡，其中 67.7% 死于疾病进展。报告了额外的亚组分析和长期安全性总结。大量使用的 RWCP 治疗方案和不良的临床结果证实了 RRMM 的 TCE 患者缺乏标准化治疗，突出表明需要具有新机制的新治疗方法。