An update on drug combinations for treatment of myeloma

Abstract

Multiple myeloma is the second most common haematological malignancy. It is becoming increasingly manageable with conventional and high-dose chemotherapy but there remains a critical need to develop both new drugs and combinations to improve long-term outcomes. Novel biological therapies that specifically target myeloma cells and/or their microenvironmental interactions are being developed that are highly effective, both as single agents and as combinations. Chief among these new agents are the proteasome inhibitor, bortezomib, and the immunomodulatory agents, thalidomide and lenalidomide. These drugs show improved single agent activity that is enhanced in combination. However, many drugs that are being developed in this setting may only have limited single agent activity, but combination use with these and other agents represents a very exciting way of targeting important pathogenic pathways crucial in myeloma development. This represents a challenge for both drug development and clinical trial evaluation, which has the potential to revolutionise the clinical management of myeloma and a paradigm for drug development in other diseases.

Immunophenotypic and cytogenetic evolution patterns of the neoplastic plasma cells in multiple myeloma relapsed after stem cell transplant

“…The use of novel chemotherapeutic agents in combination with stem cell transplantation (SCT) has significantly increased the overall survival of patients with MM [20,21]. However, the disease remains incurable and demonstrates a significant shortening of life expectancy.…”

In vitro and in vivo rationale for the triple combination of panobinostat (LBH589) and dexamethasone with either bortezomib or lenalidomide in multiple myeloma

“…2 Preliminary data indicate that the combination of compounds which simultaneously target multiple tumorigenic pathways induces a more effective and lasting anti-tumor response in different malignancies. 1,[3][4][5][6] Therefore, there is a need for the development of optimal combinations of these novel agents in order to improve the survival of patients with myeloma.…”

Therapeutic Utility of Proteasome Inhibitors for Acute Leukemia

“…Another clinical success for the same disease has been the approval of the immunomodulatory agent thalidomide [74]. Given their distinct mechanisms of action, a logical question was to address the clinical efficacy of the two drugs together [99]. Bortezomib and thalidomide were evaluated in 79 patients with advanced or refractory multiple myeloma.…”