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Quality of life


healing in patients who obtain durable complete remissions of MM. Recently, new techniques such as low-dose computed tomography (CT), magnetic resonance (MR) and positron emission tomography (PET) integrated with CT have demonstrated some advantages over standard X-rays in terms of sensibility, ability to identify MM in soft tissues and panoramic view of the skeleton.3–5 According to recent guidelines, two or more lesions recognised by one of the previously described techniques will indicate active bone disease and need for treatment.6


However, criteria for


diagnosis and monitoring still need to be standardised and validated in prospective clinical trials and in daily practice. Another developing field is the treatment of bone disease by bisphosphonates, namely pamidronate and zolendronate, to prevent skeletal events (new bone lytic lesions and fractures) and reduce bone pain in MM patients.7


A paper by Morgan et al8


showed an additive survival advantage for patients with MM receiving anti-myeloma therapy and continuous treatment with zolendronate, regardless of bone lesions. Therefore, future clinical studies should address the issue of duration of bisphosphonates treatment, balancing bone positive effects and risks, such as renal failure and jaw osteonecrosis, and taking into account quality of disease response to anti-myeloma treatments.


Management of unfit/frail elderly patients


6


Large randomised trials in patients older than 65 years or ineligible for autologous stem cell transplantation demonstrated the superiority of the combination of standard melphalan–prednisone (MP) with either thalidomide (MPT) or bortezomib (VMP) in comparison with MP alone in terms of complete responses and progression-free survival,9–11 changing dramatically the objectives of the treatment in elderly patients and moving from palliation to long-term remission. However, novel agents can cause non-haematological toxicities, namely cardiac adverse events, polyneuropathy, thromboembolism and infections, that led to therapy discontinuation in up to 30% of the patients in the previously mentioned clinical studies, so that these regimens cannot be widely applied ‘tout court’ in clinical practice. Of consequence, in real life, elderly patients, particularly if older


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than 75 years or suffering from other comorbidities, have been likely to be excluded from new drugs or to be under-treated because of precocious therapy suspension or application of arbitrary schedules with reduced dose of drugs. One of the crucial features of the elderly population is its great


assessment (CGA).12


Because CGA


requires a multidisciplinary approach and is time-consuming, it has been applied neither in prospective studies in elderly MM patients nor in clinical practice. International guidelines have recommended the use of a geriatric assessment to evaluate the patients’


“Advances in diagnostics and treatment strategies have converted MM into a chronic disease, allowing patients to survive for several years and to receive multiple lines of effective therapy”


heterogeneity, that cannot be sufficiently captured by chronological age or by functional status based on Karnofsky or Eastern Cooperative Oncology Group (ECOG) performance status, but needs a more complex evaluation in terms of number and severity of comorbid medical conditions, patient’s ability to complete activities of daily living (ADLs) and instrumental ADLs (iADLs), cognition, nutritional status, psychological condition, social support and a review of the patient’s medications, that has been known as comprehensive geriatric


cognitive and functional status and comorbidities,13


but the optimal tool needs


to be established. Given the fact that almost 50% of the MM patients are older than 65 years and that survival improvement in the last two decades has been inferior in the elderly in comparison with younger patients, it is crucial to develop and validate criteria for evaluating biological age in MM patients and to investigate in prospective clinical trials appropriate regimens and dosage of anti- myeloma therapies as well as supportive and prophylactic treatments for unfit/frail


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