Haematological cancer: Where are we now with the treatment of multiple myeloma?

• Published in: Nature reviews. Clinical oncology Vol. 14; no. 8; p. 461
• Main Authors: Morgan, Gareth J, Rasche, Leo
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 01.08.2017
• Subjects: Blood cancer; Blood diseases; Cancer; Cancer therapies; Combination chemotherapy; Drug therapy; Endoplasmic reticulum; Hematology; Hematopoietic stem cells; Lenalidomide; Multiple myeloma; Proteasomes; Stem cell transplantation; Testing
• ISSN: 1759-4774; 1759-4782; 1759-4782
• DOI: 10.1038/nrclinonc.2017.82

The past decade has seen a revolution in the treatment of patients with multiple myeloma. Before this time, the standard treatment approach for younger, fitter patients (with no specific age cut off) able to tolerate the adverse effects was high-dose melphalan with autologous stem-cell transplantation (ASCT) rescue, with melphalan and prednisolone (MP) as the established standard therapy for older, less-fit patients less able to tolerate the adverse effects of intensive chemotherapy. The revolution in myeloma outcomes was driven by the introduction of agents, such as bortezomib (Velcade, V) and lenalidomide (Revlimid, R). Both agents have distinct mechanisms of action: bortezomib directly inhibits the proteasome, preventing degradation of key cellular intermediates and resulting in endoplasmic reticulum stress; lenalidomide is an immunomodulatory agent that modifies the ubiquitin-ligase activity of cereblon, and indirectly targets the haematopoietic transcription factors Ikaros and Aiolos for degradation via the proteasome, both in myeloma cells as well as in immune cells, which enhances the activity of natural killer cells.