Ri Masaki, Iida Shinsuke, Saito Kosuke, Saito Yoshiro, Maruyama Dai, Asano Arisa, Fukuhara Suguru, Tsujimura Hideki, Miyazaki Kana, Ota Shuichi, Fukuhara Noriko, Negoro Eiju, Kuroda Junya, Yoshida Shinichiro, Ohtsuka Eiichi, Norifumi Tsukamoto, Tabayashi Takayuki, Takayama Nobuyuki, Saito Toko, Suzuki Yasuhiro, Harada Yasuhiko, Mizuno Ishikazu, Yoshida Isao, Maruta Masaki, Takamatsu Yasushi, Katsuya Hiroo, Yoshimitsu Makoto, Minami Yosuke, Kanato Keisuke, Munakata Wataru, Nagai Hirokazu
Department of Hematology and Oncology, Nagoya City University Hospital, Nagoya, Japan.
Division of Medicinal Safety Science, National Institute of Health Sciences, Kawasaki, Japan.
Cancer Chemother Pharmacol. 2025 Jan 24;95(1):29. doi: 10.1007/s00280-025-04752-1.
A comprehensive analysis of metabolites (metabolomics) has been proposed as a new strategy for analyzing liquid biopsies and has been applied to identify biomarkers predicting clinical responses or adverse events associated with specific treatments. Here, we aimed to identify metabolites associated with bortezomib (Btz)-related toxicities and response to treatment in newly diagnosed multiple myeloma (MM).
Fifty-four plasma samples from transplant-ineligible MM patients enrolled in a randomized phase II study comparing two less-intensive regimens of melphalan, prednisolone and Btz (MPB) were subjected to the lipidomic profiling analysis. The amount of each lipid metabolite in plasma obtained prior to MPB therapy was compared to toxicity grades and responses to MPB therapy.
High levels of 7 phospholipids (4 lysophosphatidylcholines and 3 phosphatidylcholines) were observed in cases with Btz-induced ≥ grade 2 peripheral neuropathy (BiPN) (n = 11). In addition, low levels of 3 fatty acids (FAs)-FA (18:2), FA (18:1), and FA (22:6)-were observed in patients who developed severe skin disorders ≥ grade 2 (n = 10). No metabolite significantly associated with treatment response was identified.
We conclude that levels of specific plasma lipid metabolites are associated with the severity of BiPN and skin disorders in patients with MM. These metabolites may serve as candidate biomarkers to predict Btz-induced toxicity in patients with MM before initiating Btz-containing therapy.
全面分析代谢物（代谢组学）已被提议作为分析液体活检的一种新策略，并已应用于识别预测与特定治疗相关的临床反应或不良事件的生物标志物。在此，我们旨在识别与硼替佐米（Btz）相关毒性以及新诊断的多发性骨髓瘤（MM）患者治疗反应相关的代谢物。
对参加一项随机II期研究的54例不符合移植条件的MM患者的血浆样本进行脂质组学分析，该研究比较了美法仑、泼尼松龙和Btz（MPB）的两种强度较低的治疗方案。将MPB治疗前获得的血浆中每种脂质代谢物的含量与毒性分级和对MPB治疗的反应进行比较。
在发生Btz诱导的≥2级周围神经病变（BiPN）的病例（n = 11）中观察到7种磷脂（4种溶血磷脂酰胆碱和3种磷脂酰胆碱）水平较高。此外，在发生≥2级严重皮肤疾病的患者（n = 10）中观察到3种脂肪酸（FAs）——FA（18:2）、FA（18:1）和FA（22:6）水平较低。未发现与治疗反应显著相关的代谢物。
我们得出结论，MM患者血浆中特定脂质代谢物的水平与BiPN和皮肤疾病的严重程度相关。这些代谢物可能作为候选生物标志物，在开始含Btz治疗前预测MM患者Btz诱导的毒性。
