Lipidomic profiling of plasma from patients with multiple myeloma receiving bortezomib: an exploratory biomarker study of JCOG1105 (JCOG1105A1).

IF 2.7 4区医学 Q3 ONCOLOGY Cancer Chemotherapy and Pharmacology Pub Date : 2025-01-24 DOI:10.1007/s00280-025-04752-1

Masaki Ri, Shinsuke Iida, Kosuke Saito, Yoshiro Saito, Dai Maruyama, Arisa Asano, Suguru Fukuhara, Hideki Tsujimura, Kana Miyazaki, Shuichi Ota, Noriko Fukuhara, Eiju Negoro, Junya Kuroda, Shinichiro Yoshida, Eiichi Ohtsuka, Tsukamoto Norifumi, Takayuki Tabayashi, Nobuyuki Takayama, Toko Saito, Yasuhiro Suzuki, Yasuhiko Harada, Ishikazu Mizuno, Isao Yoshida, Masaki Maruta, Yasushi Takamatsu, Hiroo Katsuya, Makoto Yoshimitsu, Yosuke Minami, Keisuke Kanato, Wataru Munakata, Hirokazu Nagai

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引用次数: 0

Abstract

Purpose: 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).

Methods: 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.

Results: 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.

Conclusion: 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.

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来源期刊

Cancer Chemotherapy and Pharmacology 医学-药学

CiteScore

6.10

自引率

3.30%

发文量

116

审稿时长

2.5 months

期刊介绍： Addressing a wide range of pharmacologic and oncologic concerns on both experimental and clinical levels, Cancer Chemotherapy and Pharmacology is an eminent journal in the field. The primary focus in this rapid publication medium is on new anticancer agents, their experimental screening, preclinical toxicology and pharmacology, single and combined drug administration modalities, and clinical phase I, II and III trials. It is essential reading for pharmacologists and oncologists giving results recorded in the following areas: clinical toxicology, pharmacokinetics, pharmacodynamics, drug interactions, and indications for chemotherapy in cancer treatment strategy.