Perspectives on the Risk-Stratified Treatment of Multiple Myeloma

Abstract

Summary: The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article discusses the principles that can enable the rational and effective development of therapeutic approaches for high-risk multiple myeloma.

Inhibition of PI3K Class IA Kinases Using GDC-0941 Overcomes Cytoprotection of Multiple Myeloma Cells in the Osteoclastic Bone Marrow Microenvironment Enhancing the Efficacy of Current Clinical Therapeutics

“…Multiple myeloma (MM) remains an incurable haematological malignancy despite major advances in the development of new therapeutic agents and the improvement in survival. The battery of drugs and therapeutic combinations available against MM has largely expanded in the last two decades with the introduction of the next generation proteasome inhibitors carfilzomifb and ixazomib, the immunomodulators lenalidomide and pomalidomide, the histone deacetylase inhibitor panobinostat, as well as newly developed antibody based therapies elotuzumab and daratumumab [1][2][3], bispecific antibodies targeting BCMA, GPRC5d, and FcRH5, and cell immunotherapy [4]. However, at present no approved personalised treatment pathways exist based on patterns of genetic abnormalities, the disease stage, and the efficacy of a particular type or sequence of drug treatments [2,3].…”

“…The battery of drugs and therapeutic combinations available against MM has largely expanded in the last two decades with the introduction of the next generation proteasome inhibitors carfilzomifb and ixazomib, the immunomodulators lenalidomide and pomalidomide, the histone deacetylase inhibitor panobinostat, as well as newly developed antibody based therapies elotuzumab and daratumumab [1][2][3], bispecific antibodies targeting BCMA, GPRC5d, and FcRH5, and cell immunotherapy [4]. However, at present no approved personalised treatment pathways exist based on patterns of genetic abnormalities, the disease stage, and the efficacy of a particular type or sequence of drug treatments [2,3]. Additionally, the great majority of MM patients will relapse and undergo progression and currently there are no specific biomarkers that can predict the best therapy to intervene at this disease stage [1,5].…”

Circulating Tumour Cells, Cell Free DNA and Tumour-Educated Platelets as Reliable Prognostic and Management Biomarkers for the Liquid Biopsy in Multiple Myeloma

“…Multiple myeloma (MM) is a malignancy due to the clonal growth of plasma cells (PCs); it is a not curable condition and MM subjects undertake heavy therapies with longer or shorter intervals of remission before a relapse happens, thus making a new therapy to start. With the discovery of new drugs and therapeutical procedures, patients’ survival has increased to 50% (five years) and 29% (ten years) in 2018 with respect to 37% of 5-year-survival between 2005 and 2009 [ 1 , 2 , 3 ].…”

A novel prognostic model based on pyroptosis-related genes for multiple myeloma

“…According to statistics, approximately 100, 000 patients die from MM every year worldwide [3]. To predict patient prognosis more precisely and make an optimal therapy decision, accurate risk strati cation is important, while current MM staging systems lack sensitivity and speci city in a proportion of patients, and uncovering other prognostic factors is of great signi cance [4,5].…”