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Quality of life

MM patients. An important advance in this field has been recently reported by the International Myeloma Working Group, that has identified a scoring system, based on age, comorbidities, ability in ADLs and iADLs and has demonstrated that it predicts mortality and risk of severe toxicity in a pooled analysis of 869 individual newly diagnosed elderly patients from three prospective trials, proposing this score for the measurement of frailty in MM patients.14


Polyneuropathy is a frequent side effect of thalidomide and/or bortezomib therapy. Clinical symptoms vary according to the involved drug. Thalidomide typically induces sensory neuropathy of leg extremities, with numbness, paresthesias and ataxia and is dose-dependent, even if a genetic predisposition has been recognised. However, neurotoxicity is the predominant adverse effect causing drug withdrawal in 30–50% of patients during maintenance after autologous transplantation in young patients and after MPT (melphalan– thalidomide–prednisone) regimen in elderly patients.15

Therefore, thalidomide

maintenance has not been widely applied in clinical practice, although its efficacy has been established by several trials, and more tolerated and less neurotoxic drugs such as lenalidomide have been successfully used.16,17

Bortezomib therapy frequently results in distal painful polyneuropathy that is not generally dose-related and can be more unpredictable than thalidomide neurotoxicity. Management of bortezomib neurotoxicity requires: ● Assessment of baseline neurologic symptoms related to causes other than MM therapy, such as diabetes, vitamin B12 deficiency or MM-related factors

● Frequent careful clinical monitoring ● Innovative schedules of bortezomib therapy

● New proteosomal inhibitors. Nerve electrophysiological studies do not reliably predict polyneuropathy and careful clinical evaluation and patient self-reporting instruments may be preferable. Frequency and severity of neurotoxicity have been reduced significantly by administering bortezomib once weekly instead of twice weekly, especially in elderly patients11

and by

changing route of administration from IV to SC.18


Moreover, the new proteosomal inhibitors such as carfilzomib19 that had been already

and the oral

experimented in relapse-refractory MM patients, are less neurotoxic and could be used in continuous treatment of newly diagnosed MM patients and in elderly patients.


Advances in MM diagnostics and strategies of treatment have converted MM into a chronic disease, allowing patients to survive for several years and to receive multiple lines of effective therapy. Physicians have to be ready to choose the appropriate treatment on the basis of the biological features of myeloma and the personal history of the patients and one useful instrument at this stage could be the above-mentioned score of geriatric assessment in elderly patients. When treatment starts, physicians should improve tolerability of the therapies and manage toxicities. At this stage, they will need more and more information about the impact of treatments on quality of life. In addition to the traditional medical examination, self-reported questionnaires such as those proposed by EORTC21

could be useful tools

for measuring QoL, limiting inter-operator variability and allowing comparison during the course of the treatment. ●

References 1. Brenner H, Gondos A, Pulte D. Recent major improvement in long-term survival of younger patients with multiple myeloma. Blood 2008;111:2521–6.

2. Kumar SK et al. Improved survival in multiple myeloma and the impact of novel therapies. Blood 2008;111:2516–20.

3. Zamagni E et al. A prospective comparison of 18F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance and whole-body planar radiographs in the assessment of bone disease in newly diagnosed multiple myeloma. Haematologica 2007;92:50–5.

4. Usmani SZ et al. Prognostic implication of serial 18-fluoro-deoxyglucose emission tomography in multiple myeloma treated with total therapy 3. Blood 2013;121:1819–23.

5. Kristinsson SY et al. Bone disease in multiple myeloma and precursor disease: novel diagnostic approaches and implications on clinical management. Expert Rev Mol Diagn 2011;11(6): 593–603.

6. Rajkumar SV et al. lnternational Myeloma Working Group updated criteria for the diagnosis of multiple myeloma. Lancet Oncol 2014;15(12):e538–48.

7. Berenson JR et al. American Society of Clinical Oncology clinical practice guidelines: the role of bisphosphonates in multiple myeloma.J Clin Oncol 2002;20(17):3719–36.

8. Morgan GJ et al. Effects of induction and

maintenance plus long-term bisphosphonates on bone disease in patients with multiple myeloma: the Medical Research Council Myeloma IX Trial. Blood 2012;119(23):5374–83.

9. Fayers PM et al. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. Blood 2011;118:1239–47.

10. Mateos MV et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance etreatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 2010;11:934–41.

11. Palumbo A et al. Bortezomib-melphalan- prednisone-thalidomide followed by maintenance with bortezomib-thalidomide compared with bortezomib melphalan prednisone for initial treatment of multiple myeloma: updated follow-up and improved survival. J Clin Oncol 2014;32: 634–40.

12. Sternberg SA et al. The identification of frailty: a systematic literature review. J Am Geriatr Soc 2011;59:2129–38.

13. Palumbo A et al. Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN). Blood 2011;118:4519–29.

14. Palumbo A et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 2015;125:20170–5

15. Morgan GJ et al. The role of maintenance thalidomide therapy in multiple myeloma: MRC Myeloma IX results and meta-analysis. Blood 2012;119:7–15

16. Attal M et al. Lenalidomide maintenance after autologous stem cell transplantation for multiple myeloma. N Engl J Med 2012;10:1782–91.

17. McCarthy PL et al. Lenalidomide after stem-cell transplantation for multiple myeloma. N Engl J Med 2012;10:1770–81.

18. Moreau P et al. Subcutaneous versus intravenous administration of bortezomib in patients with relapsed multiple myeloma: a randomised, phase 3, non-inferiority study. Lancet Oncol 2011;12: 431–40.

19. Stewart AK et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med 2015;372(2):142–52.

20. Richardson PG et al. Phase 1 study of twice-weekly ixazomib, an oral proteasome inhibitor, in relapsed/refractory multiple myeloma patients. Blood 2014;124(7):1038–46.

21. Dimopoulos M et al. Factors that influence health-related quality of life in newly diagnosed patients with multiple myeloma aged - 65 years treatedwith melphalan, prednisone and lenalidomide followed by lenalidomide maintenance: results of a randomized trial. Leukemia Lymphoma 2014 55(7):1489–97.


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