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

2025-01-24
Cancer chemotherapy and pharmacology 95(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

PubMed: 39853402
DOI: 10.1007/s00280-025-04752-1

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 11
Population: 54 transplant-ineligible newly diagnosed multiple myeloma patients
Methods: lipidomic profiling of plasma samples obtained prior to MPB therapy; comparison of metabolite levels to toxicity grades and responses
Funding: Unclear

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.