Department of Pharmaceutical Services, University of California, San Francisco, San Francisco, CA, USA.
Department of Pharmacy Services, University of California, Davis, Sacramento, CA, USA.
J Oncol Pharm Pract. 2023 Oct;29(7):1715-1724. doi: 10.1177/10781552221150935. Epub 2023 Feb 2.
For patients with multiple myeloma (MM) who have undergone autologous stem cell transplant (auto-SCT), the immunomodulatory agent lenalidomide is a first-line option for maintenance therapy. Because longer durations of lenalidomide maintenance are associated with improved survival, identifying strategies to avoid premature cessation of maintenance is an important priority in the post-transplant setting.
The primary objective of this analysis was to identify specific clinical predictors of lenalidomide treatment duration that could guide optimal medication management. Key secondary objectives included predictors of intolerable toxicity, rationale for lenalidomide dose reduction/discontinuation, and characterization of dose adjustments.
This retrospective, multi-center cohort study included adults with MM who underwent auto-SCT and initiated maintenance lenalidomide between 01/01/2012 and 02/28/2021. Variables assessed as potential predictors of maintenance duration or intolerable toxicity included age, body mass index (BMI), Eastern Cooperative Oncology Group (ECOG) performance status at time of auto-SCT, renal function, initial lenalidomide dose, use of combination maintenance therapy, and cytogenetic risk category.
Among 299 patients included, the median age at time of auto-SCT was 62 years (range 30-77). The majority of patients had standard-risk cytogenetics (64%) and an ECOG performance status of 0 or 1 (72%). In the overall population, the median duration of maintenance was 1.3 years (range 0.3-8.6 years). The median initial dose of lenalidomide was 10 mg daily (range 2.5-25 mg). During the study period, 35% of patients had a dose reduction due to toxicity, 21% stopped lenalidomide due to disease progression, and 19% stopped due to toxicity. Multivariate linear regression analyses did not identify any significant predictors of lenalidomide duration or discontinuation due to intolerable toxicity. The most frequently reported toxicities leading to discontinuation were cytopenias, rash, and fatigue.
This analysis did not identify any significant risk factors to predict the duration of lenalidomide maintenance or discontinuation for toxicity following auto-SCT in patients with MM. While limited by the retrospective design and relatively small sample size, our findings suggest that lenalidomide dose reductions based on patient co-morbidities or performance status may not substantially affect the duration of lenalidomide maintenance.
对于接受自体干细胞移植（auto-SCT）的多发性骨髓瘤（MM）患者，免疫调节剂来那度胺是维持治疗的一线选择。由于延长来那度胺维持治疗的时间与改善生存相关，因此确定避免提前停止维持治疗的策略是移植后环境中的一个重要优先事项。
本分析的主要目的是确定可指导最佳药物管理的来那度胺治疗持续时间的具体临床预测因素。主要次要目标包括不耐受毒性的预测因素、来那度胺剂量减少/停药的理由以及剂量调整的特征。
这项回顾性、多中心队列研究纳入了 2012 年 1 月 1 日至 2021 年 2 月 28 日期间接受 auto-SCT 并开始维持来那度胺治疗的 MM 成年患者。评估为维持持续时间或不耐受毒性的潜在预测因素包括年龄、体重指数（BMI）、auto-SCT 时的东部合作肿瘤学组（ECOG）表现状态、肾功能、初始来那度胺剂量、联合维持治疗的使用以及细胞遗传学风险类别。
在 299 例患者中，auto-SCT 时的中位年龄为 62 岁（范围 30-77 岁）。大多数患者具有标准风险细胞遗传学（64%）和 ECOG 表现状态为 0 或 1（72%）。在总体人群中，维持治疗的中位持续时间为 1.3 年（范围 0.3-8.6 年）。初始来那度胺剂量的中位数为 10mg 每日（范围 2.5-25mg）。在研究期间，由于毒性，35%的患者减少了剂量，21%的患者因疾病进展而停止了来那度胺治疗，19%的患者因毒性而停止了治疗。多变量线性回归分析未发现任何与来那度胺持续时间或因不耐受毒性而停药相关的显著预测因素。导致停药的最常见毒性包括血细胞减少症、皮疹和疲劳。
本分析未发现任何显著的风险因素来预测多发性骨髓瘤患者自体干细胞移植后来那度胺维持治疗或因毒性而停药的时间。虽然受到回顾性设计和相对较小的样本量的限制，但我们的研究结果表明，根据患者合并症或表现状态进行来那度胺剂量减少可能不会显著影响来那度胺维持治疗的时间。
