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Multiple myeloma (MM) accounts for 10% of haematological malignancies.1,2 Its frequency is constantly increasing with the age of the general population. Currently, <40% of myeloma patients are <65 years of age, while the incidence of elderly MM patients (>65 years of age) will increase in the near future, in part due to the increased lifespan of the population and also because of the progress made in the field of myeloma treatments.
In newly diagnosed young MM patients (<65 years of age), the standard treatment is autologous stem cell transplantation (ASCT). For elderly (>65 years of age) or unfit patients, conventional chemotherapy (CC) is the best choice. The adverse prognostic effects of age in myeloma predominantly relate to co-morbidity, performance status, lowered physiological reserve, social support and undertreatment of the tumour. Novel, more effective treatment approaches are now available to improve outcome and extend survival.
Recently, agents with a specific and innovative mechanism of action, such as the immunomodulant drugs (IMiDs) thalidomide and lenalidomide, and bortezomib, the first proteasome inhibitor, have been shown to be safe and effective in both newly diagnosed and relapsed/refractory settings.
Thalidomide and lenalidomide inhibit angiogenesis, stimulate T and natural killer (NK) cells and interfere with cytokines that play a role in the growth and the acquisition of chemoresistance of MM cells.3 Bortezomib is the first in the class of proteasome inhibitors and inhibits the 26S proteasome subunit that is responsible for transcription and degradation of the protein involved in cell proliferation and metabolism.4
Until the 2000s, the association of melphalan and prednisone (MP) represented the gold standard treatment for patients >65 years of age or not eligible for ASCT.5 Another option was a high dose of glucocorticoids alone or in combination with other agents, such as alkylators.6 In the last 10 years, the association of the new agents with these older drugs has been shown to increase response rates (RR), in particular the complete remission (CR) rate, and to improve outcomes.
In this article, we will focus on the most recent treatments for elderly myeloma patients, with particular attention paid to the balance between efficacy and safety.