Carfilzomib and pomalidomide: recent advances in the treatment of multiple myeloma

Pharmacotherapy. 2014 Sep;34(9):927-40. doi: 10.1002/phar.1463. Epub 2014 Jul 19.

Abstract

Multiple myeloma is a hematologic malignancy characterized by plasma cell clonal expansion as well as end-organ damage due to increased levels of monoclonal proteins in both the plasma and urine. The clinical syndrome is characterized by hypercalcemia, renal insufficiency, anemia, and bone involvement that leads to pathologic fractures. This progressive disease can result in significant patient morbidity and mortality. Despite advances with treatment options and autologous stem cell transplantation, multiple myeloma remains incurable. Current front-line therapies include proteasome inhibitors, immunomodulators, anthracyclines, and steroids. Due to the advent of the immunomodulatory agents thalidomide and lenalidomide, as well as the proteasome inhibitor bortezomib, overall survival in patients with multiple myeloma has improved greatly. However, once patients progress through front-line therapy and have relapsed or refractory disease, treatment options have historically been very limited. Carfilzomib, a second-generation proteasome inhibitor, has shown impressive response rates as a single agent in the relapsed and refractory patient setting; this includes patients who are refractory to previous bortezomib therapy. In addition, a third-generation immunomodulator, pomalidomide, has also shown promising results in a similar patient population, including those patients who have been shown to be refractory to lenalidomide and bortezomib. Adverse effects of both of these medications have been considered tolerable in the relapsed or refractory population, especially considering the benefits that have been shown. Continuing clinical research will reveal the utility of these agents in combination regimens or in a front-line setting for patients with multiple myeloma.

Keywords: carfilzomib; multiple myeloma; oncology; pharmacy practice; pomalidomide.

Publication types

  • Review

MeSH terms

  • Angiogenesis Inhibitors / adverse effects
  • Angiogenesis Inhibitors / pharmacology
  • Angiogenesis Inhibitors / therapeutic use
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use
  • Humans
  • Multiple Myeloma / drug therapy*
  • Multiple Myeloma / pathology
  • Oligopeptides / adverse effects
  • Oligopeptides / pharmacology
  • Oligopeptides / therapeutic use*
  • Survival Rate
  • Thalidomide / adverse effects
  • Thalidomide / analogs & derivatives*
  • Thalidomide / pharmacology
  • Thalidomide / therapeutic use
  • Treatment Outcome

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Oligopeptides
  • Thalidomide
  • carfilzomib
  • pomalidomide