Yong Kwee, Einsele Hermann, Schecter Jordan M, Roccia Tito, Deraedt William, Lendvai Nikoletta, Slaughter Ana, Lonardi Carolina, Connors Kaitlyn, Qi Keqin, Londhe Anil, Carson Robin, Kharat Akshay, Cost Patricia, Valluri Satish, Mendes João, Pacaud Lida, Patel Nitin, Florendo Erika, Dhakal Binod
University College London Cancer Institute, London, UK.
University Hospital of Würzburg, Medizinische Klinik und Poliklinik II, Würzburg, Germany.
Eur J Cancer. 2025 Jan 17;215:115157. doi: 10.1016/j.ejca.2024.115157. Epub 2024 Nov 29.
The introduction of proteasome inhibitors (PIs) and lenalidomide as treatment for newly diagnosed multiple myeloma (MM) has led to an increased population of lenalidomide-refractory patients. Limited data are available characterizing current treatments and outcomes in this difficult-to-treat population.
Individual patient-level data were analyzed from the treatment arms of multiple daratumumab studies, including APOLLO, CASTOR, CANDOR, EQUULEUS, ALCYONE, MAIA, GRIFFIN, POLLUX, and CASSIOPEIA. Included patients were PI exposed and lenalidomide refractory, received 1-3 prior lines of therapy (LOT), and had an Eastern Cooperative Oncology Group performance status < 2. Treatments and outcomes were analyzed by number of prior LOT in the lenalidomide-refractory population. Time to next treatment (TTNT), progression-free survival (PFS), and overall survival (OS) were estimated using the Kaplan-Meier method.
Out of 4764 patients, 915 patients (prior LOT, one [n = 114]; two [n = 462]; three [n = 339]) met inclusion criteria. Median follow-up was 29·7 months (range 28·0-31·7). The overall response rate was 55·4 %. Estimated median TTNT was 9·7 months, median PFS was 10·0 months, and median OS was 27·5 months. Response rates and PFS decreased as number of prior LOT increased. Prognostic factors for response, TTNT, PFS, and OS included International Staging System stage, baseline plasmacytoma status, baseline hemoglobin, anti-CD38-refractory status, and cytogenetic risk status.
Lenalidomide-refractory patients treated with 1-3 prior LOT have poor PFS and OS, which generally worsen with each additional LOT, highlighting the need for new and effective treatments for this population.
蛋白酶体抑制剂（PIs）和来那度胺被引入用于新诊断的多发性骨髓瘤（MM）的治疗，导致来那度胺难治性患者群体增加。关于这一难以治疗的患者群体当前治疗方法和治疗结果的数据有限。
对多个达雷妥尤单抗研究的治疗组进行个体患者水平数据分析，这些研究包括APOLLO、CASTOR、CANDOR、EQUULEUS、ALCYONE、MAIA、GRIFFIN、POLLUX和CASSIOPEIA。纳入的患者曾接受过PI治疗且对来那度胺难治，接受过1 - 3线既往治疗（LOT），东部肿瘤协作组体能状态<2。在来那度胺难治性患者群体中，根据既往LOT的数量对治疗方法和治疗结果进行分析。使用Kaplan - Meier方法估计下次治疗时间（TTNT）、无进展生存期（PFS）和总生存期（OS）。
在4764例患者中，915例患者（既往LOT，一线[n = 114]；二线[n = 462]；三线[n = 339]）符合纳入标准。中位随访时间为29.7个月（范围28.0 - 31.7个月）。总缓解率为55.4%。估计中位TTNT为9.7个月，中位PFS为10.0个月，中位OS为27.5个月。缓解率和PFS随着既往LOT数量的增加而降低。缓解、TTNT、PFS和OS的预后因素包括国际分期系统分期、基线浆细胞瘤状态、基线血红蛋白、抗CD38难治性状态和细胞遗传学风险状态。
接受过1 - 3线既往LOT治疗的来那度胺难治性患者的PFS和OS较差，且通常随着每增加一线治疗而恶化，这凸显了为该患者群体开发新的有效治疗方法的必要性。
