Towards Molecular Profiling in Multiple Myeloma: A Literature Review and Early Indications of Its Efficacy for Informing Treatment Strategies

Abstract

Multiple myeloma (MM), the second most common hematologic malignancy, is characterized by the clonal expansion of plasma cells. Despite dramatic improvements in patients′ survival over the past decade due to advances in therapy exploiting novel molecular targets (immunomodulatory drugs, proteasome inhibitors and monoclonal antibodies), the treatment of relapsed and refractory disease remains challenging. Recent studies confirmed complex, dynamic, and heterogeneous genomic alterations without unifying gene mutations in MM patients. In the current review, we survey recent therapeutic strategies, as well as molecular profiling data on MM, with emphasis on relapsed and refractory cases. A critical appraisal of novel findings and of their potential therapeutic implications will be discussed in detail, along with the author’s own experiences/views.

Hematogenous extramedullary relapse in multiple myeloma ‐ a multicenter retrospective study in 127 patients

“…Recently, immune therapies, including bispecific T‐cell engagers and autologous T cells expressing a tumor‐specific chimeric antigen receptor, have also shown promising responses (including a complete response) in relapsed HEMM patients . Importantly, molecular characterization (eg, BRAF, RAS/RAF mutations, etc, reported in some of HEMM relapses) may help guiding therapy . Lastly, the development of new therapies that interfere with cell homing and migration, e.g.…”

CAR-T Cells Based on Novel BCMA Monoclonal Antibody Block Multiple Myeloma Cell Growth

“…Multiple myeloma is a cancer of plasma cells characterized by clonal proliferation in the bone marrow microenvironment [ 1 ]. Multiple myeloma is the second-most common hematologic malignancy, accounting for 5–10% of all hematologic malignancies in the USA [ 2 , 3 ]. Despite recent progress in treatment, multiple myeloma remains incurable with high rates of relapsed and refractory disease [ 3 ].…”

NRF2 Is One of the Players Involved in Bone Marrow Mediated Drug Resistance in Multiple Myeloma

“…These mechanisms, including chromosome abnormalities, gene mutations, modifications of the bone marrow microenvironment with soluble factors, and/or adhesion of components and cells, all work together to tune the signal pathways that suppress the immune response and promote MM proliferation, survival, and drug resistance. Thus, knowing these mechanisms also turns on a niche for a novel therapeutic strategy to overcome drug resistance for disease treatment [ 31 , 32 , 33 , 34 ]. In this review, we discuss the mechanisms of disease progression and drug resistance from bone marrow microenvironment milieus focusing on the components and cells that sustain MM plasma cells survival and proliferation, which contribute to MM resistance.…”