Multiple myeloma: Updates for pharmacists in the treatment of relapsed and refractory disease

Abstract

There have been a number of recent advances in the treatment of patients with relapsed and refractory multiple myeloma. However, despite additional FDA-approved therapies including carfilzomib and pomalidomide as well as clinical trials investigating new combinations of existing treatments, multiple myeloma remains an incurable disease. New therapies currently in the drug development pipeline for relapsed and refractory disease include additional proteasome inhibitors (oprozomib, marizomib, ixazomib), histone deacetylase inhibitors (panobinostat, ricolinostat, quisinostat), monoclonal antibodies (daratumumab, elotuzumab, SAR650984), Bruton's tyrosine kinase inhibitors (ibrutinib), a selective inhibitor of nuclear export, and others. This review will focus on these newly developing therapies as well as the ever expanding role of the pharmacist in supportive care for patients with relapsed and refractory multiple myeloma.

CD229 is expressed on the surface of plasma cells carrying an aberrant phenotype and chemotherapy-resistant precursor cells in Multiple Myeloma

“…[12][13][14][15][16] Unfortunately, cures still remain a rare exception and most patients will eventually experience a chemotherapy-refractory relapse of the disease. 18 However, the number of promising therapeutic targets expressed on the surface of the bulk of myeloma cells as well as the chemotherapy-resistant and myeloma-propagating subpopulation of PC is still very limited.…”

Multiple myeloma in the marrow: pathogenesis and treatments

“…Exciting, novel strategies to inhibit the vicious cycle and osteolysis and heal osteolytic lesions on the basis of a better understanding of the basic biology of the disease and the BMM are in development. 6,[208][209][210] These microenvironment-targeting treatments, in conjunction with ASCT, will induce better patient outcomes, and are leading the way in the treatment of relapsed, refractory MM. 121 Interesting new directions may target OCs and OBs, as we learn more about the roles of these and other cells in the BM.…”

The HDAC6‐selective inhibitor is effective against non‐Hodgkin lymphoma and synergizes with ibrutinib in follicular lymphoma

“…Although tubacin is the first and most extensively studied HDAC6‐selective inhibitor, it is largely used as a research tool rather than a potential drug due to non‐druggable qualities . Ricolinostat (ACY‐1215) is the only first‐in‐class clinically relevant HDAC6 inhibitor and is currently being tested in clinical trials in multiple myeloma and lymphoid malignancies . In addition, preclinical data with numerous cancer cell lines support the synergistic effects of HDAC inhibitors, such as vorinostat or panobinostat, with various anticancer therapies .…”