Progress and Paradigms in Multiple Myeloma

Abstract

Remarkable progress has been achieved in multiple myeloma, and patient median survival has been extended 3-to 4-fold. Specifically, there have been 18 newly approved treatments for multiple myeloma in the past 12 years, including seven in 2015, and the treatment paradigm and patient outcome have been transformed. The definition of patients benefitting from these therapies has been broadened. Response criteria now include minimal residual disease (MRD), assessed in bone marrow by multicolor flow cytometry or sequencing, and by imaging for extramedullary disease. Initial therapy for transplant candidates is a triplet incorporating novel therapies-that is, lenalidomide, bortezomib, and dexamethasone or cyclophosphamide, bortezomib, and dexamethasone. Lenalidomide maintenance until progression can prolong progression-free and overall survival in standard-risk multiple myeloma, with incorporation of proteasome inhibitor for high-risk disease.Studies are evaluating the value of early versus late transplant and MRD as a therapeutic goal to inform therapy. In nontransplant patients, triplet therapies are also preferred, with doublet therapy reserved for frail patients, and maintenance as described above. The availability of second-generation proteasome inhibitors (carfilzomib and ixazomib), immunomodulatory drugs (pomalidomide), histone deacetylase inhibitors (panobinostat), and monoclonal antibodies (elotuzumab and daratumumab) allows for effective combination therapies of relapsed disease as well. Finally, novel therapies targeting protein degradation, restoring autologous memory anti-multiple myeloma immunity, and exploiting genetic vulnerabilities show promise to improve patient outcome even further.

The diagnostic and prognostic value of plasma microRNA‑125b‑5p in patients with multiple myeloma

“…The specimens in this study were obtained from 41 patients who were diagnosed in accordance with the National Comprehensive Cancer Network (NCCN) clinical practice guidelines for MM at the 1st Affiliated Hospital of Nanchang University from October 2015 to July 2017 (12). Among the 41 plasma specimens from MM patients, 6 were used for microarray analysis, and 35 served as the validation set.…”

Polyclonal Immunoglobulin Recovery after Autologous Stem Cell Transplantation Is an Independent Prognostic Factor for Survival Outcome in Patients with Multiple Myeloma

“…Until now, treatment strategy for MM has been evolving rapidly by the introduction of several new classes of agents such as proteasome inhibitors (bortezomib, carfilzomib, and ixazomib), immunomodulatory drugs (thalidomide, lenalidomide, and pomalidomide), and monoclonal antibodies (elotuzumab and daratumumab) [4]. These highly effective modalities including bortezomib + lenalidomide + dexamethasone (VRd) induction and autologous stem cell transplantation (ASCT) have led to durable and deeper responses [5].…”

Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo activity against multiple myeloma

“…Multiple myeloma (MM) is the second most common haematological malignancy worldwide and is characterized by clonal proliferation of plasma cells in the bone marrow (BM). Moreover, it is defined by high levels of monoclonal protein in serum and/or urine as well as BM plasmacytosis, and is associated with bone lesions, anaemia, cytopenia, hypercalcaemia, peripheral neuropathy, and/or renal dysfunction (Anderson, ). High dose therapy [melphalan (MEL)] followed by autologous stem cell transplantation, as well as novel therapies including immunomodulatory drugs [IMiDs; thalidomide, lenalidomide (LEN) and pomalidomide], proteasome inhibitors [bortezomib (BTZ), carfilzomib and ixazomib], monoclonal antibodies (elotuzumab and daratumumab), and the histone deacetylase inhibitor, panobinostat, have markedly improved clinical outcome of MM patients (Attal et al , ).…”