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Treatment


Treating the elderly patient


Combination therapy based on novel agents, with or without alkylators, is the current standard of care for elderly multiple myeloma patients


Maria Victoria Mateos MD PhD Servicio de Hematología, Hospital Universitario de Salamanca, CIC, IBMCC (USAL-CSIC), Salamanca, Spain


Multiple myeloma (MM) mainly affects the elderly. Figures from the National Cancer Institute Surveillance, Epidemiology and End Results (SEER) Programme indicate a prevalence of 31 per 100,000 among 65–69-year-olds, 36 per 100,000 among 70–74-year-olds and 39 per 100,000 among people aged 80–84 years.1


UK data indicate an incidence of 60–70 per million,2 and


median age at presentation is approximately 70 years. By 2030, the number of people over 65 years old with myeloma in the US is expected to double.


A paradigm shift


Treatment of myeloma has seen a paradigm shift in recent years with a consequent increase in response and survival rates. Median overall survival (OS) rates among elderly multiple myeloma patients have increased from around 27 months with melphalan– prednisone (MP).3


The introduction of 16


novel drugs, such as bortezomib, lenalidomide and thalidomide, has, in part, contributed to improvements in median OS to around 60 months.4 Nevertheless, even greater improvements in survival have been seen in younger patients. For example, five-year relative survival among patients aged under 50 years in the US increased from 45% to 57% from 1990–92 to 2002–4. The increase among patients aged 50–59 years was 39% to 48% in the same periods. However, among patients aged


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60–69 years, five-year survival has only risen from 31% to 36% and from 27% to 29% among patients aged over 70 years in the same time period.5


Elderly people with multiple myeloma are a heterogeneous group varying from very fit, active adults who exercise regularly to those who are less active, moderately fit, through to those who are frail or severely frail and are dependent on others.5


Many patients aged over 75


years have comorbid conditions that can introduce additional complications to the presentation and management of MM. As a result, many of these patients are often excluded from clinical trials, so the evidence to support their management is limited.


Aims of treatment


The aims of treatment in elderly MM patients are primarily to:


● Prolong survival ● Delay disease progression ● Ensure good quality of life. These aims can be achieved by maximal eradication of the tumour clone through the best possible response balanced with acceptable toxicity. As people age, their risk of developing cancer increases.6


function reduces with age, which can affect drug pharmacodynamics and pharmacokinetics and thus impact efficacy and toxicity. So older patients may be more vulnerable to side effects. These factors may contribute to reduced efficacy of chemotherapy among older patients.5


Pharmacotherapy


Alkylator-based induction regimens Generally patients over 65 years of age with newly diagnosed MM are not considered for autologous stem cell transplantation (ASCT) because they are thought to be unable to tolerate the toxicity of the treatment. However, patients vary and dose reduction may mean older patients, even some over the age of 70 years, may be able to undergo the procedure.


First-line treatment of elderly MM patients who are transplant-ineligible has, for more than 30 years, been melphalan and prednisone, which is well tolerated and results in response and survival rates similar to other conventional chemotherapy, but with complete responses rates of 3–4% and OS not superior to two years.7,8


However,


newer agents such as bortezomib, lenalidomide and thalidomide used in combination with MP has led to further improvements, resulting in new


At the same time, organ


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