Proteomics-inspired precision medicine for treating and understanding multiple myeloma

ABSTRACT

Introduction: Remarkable progress in molecular characterization methods has led to significant improvements in how we manage multiple myeloma (MM). The introduction of novel therapies has led to significant improvements in overall survival over the past 10 years. However, MM remains incurable and treatment choice is largely based on outdated risk-adaptive strategies that do not factor in improved treatment outcomes in the context of modern therapies.

Areas covered: This review discusses current risk-adaptive strategies in MM and the clinical application of proteomics in the monitoring of treatment response, disease progression, and minimal residual disease (MRD). We also discuss promising biomarkers of disease progression, treatment response, and chemoresistance. Finally, we will discuss an immunomics-based approach to monoclonal antibody (mAb), vaccine, and CAR-T cell development.

Expert opinion: It is an exciting era in oncology with basic scientific knowledge translating in novel therapeutic approaches to improve patient outcomes. With the advent of effective immunotherapies and targeted therapies, it has become crucial to identify biomarkers to aid in the stratification of patients based on anticipated sensitivity to chemotherapy. As a paradigm of diseases highly dependent on protein homeostasis, multiple myeloma provides the perfect opportunity to investigate the use of proteomics to aid in precision medicine.

KEYWORDS:

• Multiple myeloma
• biomarkers
• immunomics
• proteomics
• minimal residual disease
• risk-adaptive strategies

Article highlights

• MM, a highly heterogenous disease with multiple subclones present within the tumor population of an individual patient, remains incurable and treatment choice is largely based on outdated risk-adaptive strategies that do not factor in improved treatment outcomes in the context of modern therapies.

• There are an increasing number of studies exploring the clinical application of proteomic technologies in the monitoring of treatment response, disease progression, and minimal residual disease, and the initial data look very promising.

• Mass spectrometry-based proteomics has identified new biomarker candidates of MM disease progression, treatment response, and chemoresistance.

• Mass spectrometry-based immunomics has led to the discovery of novel MM-specific T-cell epitopes and tumor-associated antigens for T cell and monoclonal antibody-based immunotherapies, respectively.

• The increasing use of proteomics has and will continue to generate huge amounts of data. The challenge moving forwards is to not become lost in the multitude of data but to instead focus on translating ‘big data’ into actionable knowledge to facilitate further progress in MM.

Declaration of Interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.