Past, Present, and a Glance into the Future of Multiple Myeloma Treatment

Abstract

Multiple myeloma (MM) is a challenging hematological cancer which typically grows in bone marrow. MM accounts for 10% of hematological malignancies and 1.8% of cancers. The recent treatment strategies have significantly improved progression-free survival for MM patients in the last decade; however, a relapse for most MM patients is inevitable. In this review we discuss current treatment, important pathways for proliferation, survival, immune suppression, and resistance that could be targeted for future treatments.

Immunotherapy of Multiple Myeloma: Current Status as Prologue to the Future

“…These advances are reflected in the dramatic improvements in the 5-year survival rates for the disease, which had risen gradually from 25% in the 1975-77 period to 32% for 1995-97 but climbed sharply to 58% during 2012-2018 as the impact of these newer modalities began to come into play [2]. The benefits of these therapeutic advances are further evidenced by such measures as accumulated survival and response data and studies demonstrating an improved quality of life [255,256]. The characterization of MM itself has changed over the years, shifting from the traditional CRAB model toward a paradigm that includes molecular and immunologically based factors that may be evidence of the disease before signs and symptoms emerge.…”

New Scaffolds of Proteasome Inhibitors: Boosting Anticancer Potential by Exploiting the Synergy of In Silico and In Vitro Methodologies

“…Six proteasome inhibitors are on the market or have been in clinical use: bortezomib, carfilzomib, ixazomib, marizomib, delanzomib, and oprozomib (Figure 2). Bortezomib has marketing authorization for the treatment of multiple myeloma and mantle cell lymphoma, while carfilzomib and ixazomib are only approved for the treatment of multiple myeloma [37][38][39][40]. The inner β rings are responsible for the proteolytic activity.…”

“…Six proteasome inhibitors are on the market or have been in clinical use: bortezomib, carfilzomib, ixazomib, marizomib, delanzomib, and oprozomib (Figure 2). Bortezomib has marketing authorization for the treatment of multiple myeloma and mantle cell lymphoma, while carfilzomib and ixazomib are only approved for the treatment of multiple myeloma [37][38][39][40]. Despite its slowly reversible mode of action, the formation of a metastable but longlasting covalent inhibitor-proteasome adduct causes an unfavorable pharmacodynamic profile since a large fraction of the intravenously administrated dose is lost due to the inhibition of proteasomes in non-tumor tissues, (e.g., red blood cells, liver, and the vascular endothelium).…”

A Study on Renal Failure Management in Patients Diagnosed With Multiple Myeloma

“…Targeted therapies, immunomodulatory agents, and proteasome inhibitors have shown promise in enhancing patient outcomes and extending survival rates. However, the effect of these treatments in managing renal function remains a subject of ongoing investigation [11]. The delicate balance between achieving optimal disease control and preserving renal health poses a clinical dilemma, further underscoring the need for evidence-based guidelines specific to the Saudi population.…”