Current Review on High-Risk Multiple Myeloma

Abstract

Apart from clinical stage, disease genetics are now recognised as important prognostic risk factors, and various new cytogenetic changes with negative prognostic impact have been identified. New technologies such as minimal residual disease detection are also playing an important role in prognostic assessment. Recent introduction of combination therapy with proteasome inhibitors and immunomodulatory drugs is showing promising results in high-risk patients and may partially abrogate the negative impact associated with some of the adverse risk factors. Recent advance has improved our understanding of high-risk multiple myeloma, and new therapeutic agents are now coming through the pipeline for this patient group with once dismal outcome.

Development and Validation of a 9-Gene Prognostic Signature in Patients With Multiple Myeloma

“…As stated above, although several novel agents for patients with MM have been introduced into clinical practice, the disease remained incurable, and the clinical outcome of patients with MM is still poor (2, 3). Thus, it is of vital importance to develop such molecular biomarkers or signature that are significantly correlated with the clinicopathological features and clinical outcome of patients with MM.…”

“…Multiple myeloma (MM), originated from malignant plasma cells secreting monoclonal M protein, represents the second most common malignancy in hematological malignancies (1–3). MM is differentiated from monoclonal gammopathy of undetermined significance (MGUS) and smoldering multiple myeloma (SMM) by the presence of end-organ damage (4, 5).…”

Final analysis of a phase 1/2b study of ibrutinib combined with carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma

“…While stem cell transplant and novel drug combinations have contributed to improved outcomes, morbidity and mortality remain high. The availability of effective combination therapies including proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) is critical, especially for high‐risk patients who historically respond well to combination therapies …”

“…The most common grade ≥3 hematologic treatment-emergent adverse events (TEAEs) were anemia and thrombocytopenia (17% each); the most common grade ≥3 non-hematologic TEAE was hypertension including proteasome inhibitors (PIs) and immunomodulatory drugs (IMIDs) is critical, especially for high-risk patients who historically respond well to combination therapies. 2,3 PIs target several anti-apoptotic proteins that allow MM cells to survive and proliferate. 4,5 The PIs bortezomib (in combination with lenalidomide) and carfilzomib are approved for the treatment of relapsed/refractory MM (RRMM).…”

Combined Selection System to Lower the Cutoff for Plasma Cell Enrichment Applied to iFISH Analysis in Multiple Myeloma

“…Translocation t(14;16)(q32;q23) leads to the juxtaposition of the immunoglobulin heavy chain (IGH) and c-musculoaponeurotic fibrosarcoma (c-MAF) oncogene loci and is considered a high risk feature [18] . Abnormalities of chromosome 1 (loss of chromosome 1p and gain of chromosome 1q) generally occur at advanced stage of the disease and have shown to be correlated with poor prognosis [19] .…”