Hartley-Brown Monique A, Weisel Katja, Bitetti Jacopo, Carter John A, McNamara Simon, Purser Molly, Palumbo Antonio, Richardson Paul G
Department of Medical Oncology, Harvard Medical School, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
Division of Hematology, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Br J Haematol. 2024 Sep;205(3):780-797. doi: 10.1111/bjh.19627. Epub 2024 Jul 19.
The growing use of frontline lenalidomide treatment in multiple myeloma (MM) is increasing the proportion of lenalidomide-refractory patients, which may limit the efficacy of subsequent lines of treatment (LOT). This systematic literature review (January 2008-October 2023) of clinical trials (CT) and real-world studies (RW) assessed treatment outcomes in adults with relapsed/refractory MM (RRMM) who were previously treated with ≥1 LOT, progressed and were lenalidomide-refractory. Medline, EMBASE and additional electronic databases were searched for articles published in English. Primary outcomes included progression-free survival (PFS), overall survival (OS) and overall/objective response rate (ORR); 24 CT and 19 RW were included. For CT, the population-weighted mean of median PFS (CT = 14) and OS (CT = 6) were shorter in the lenalidomide-refractory cohort (months: 8.8 [n = 2699] and 21.7 [n = 1066], respectively) than the intent-to-treat population (months: 13.8 [n = 5380] and 35.9 [n = 2264], respectively); the population-weighted (N = 2142) mean ORR for lenalidomide-refractory patients (CT = 18) was 56.0%. RW reported considerable variation in PFS (RW = 7), OS (RW = 8) and ORR (RW = 8); and median PFS (RW = 2; months) was lower in lenalidomide/bortezomib-refractory (5.5/5.5; n = 81/n = 25) versus lenalidomide-refractory (7.3/8.0; n = 81/n = 61) patients. These data provide evidence that clinical trials and real-world outcomes are suboptimal in lenalidomide-refractory patients with RRMM, highlighting the need to improve treatment options for this population.
在多发性骨髓瘤（MM）中，一线来那度胺治疗的使用日益增加，这使得来那度胺难治性患者的比例不断上升，这可能会限制后续治疗线（LOT）的疗效。这项对临床试验（CT）和真实世界研究（RW）进行的系统文献综述（2008年1月至2023年10月）评估了曾接受≥1线治疗、病情进展且对来那度胺难治的复发/难治性MM（RRMM）成年患者的治疗结果。检索了Medline、EMBASE和其他电子数据库中以英文发表的文章。主要结局包括无进展生存期（PFS）、总生存期（OS）和总/客观缓解率（ORR）；纳入了24项CT和19项RW研究。对于CT研究，来那度胺难治性队列的中位PFS（CT = 14）和OS（CT = 6）的人群加权均值（月数：分别为8.8 [n = 2699]和21.7 [n = 1066]）短于意向性治疗人群（月数：分别为13.8 [n = 5380]和35.9 [n = 2264]）；来那度胺难治性患者（CT = 18）的人群加权（N = 2142）平均ORR为56.0%。RW研究报告了PFS（RW = 7）、OS（RW = 8）和ORR（RW = 8）方面的显著差异；来那度胺/硼替佐米难治性患者（5.5/5.5；n = 81/n = 25）的中位PFS（RW = 2；月数）低于来那度胺难治性患者（7.3/8.0；n = 81/n = 61）。这些数据表明，在RRMM的来那度胺难治性患者中，临床试验和真实世界的结局都不理想，凸显了改善这一人群治疗选择的必要性。
