A pooled analysis of three prospective
trials involving 869 newly diagnosed elderly patients analysed the correlation of patient status with treatment discontinuation, mortality and risk of toxicity. Palumbo et al developed an additive scoring system based on age, comorbidities and cognitive and physical conditions to categorise patients as fit, intermediate fitness, unfit or frail. Median PFS in fit, unfit and frail patients was 14, 13 and 11 months, respectively. One-year OS was 96% among fit patients, 93% for unfit and 78% for frail patients. The authors say: ‘Our frailty score predicts mortality and the risk of toxicity in elderly myeloma patients. The International Myeloma Working group proposes this score for the measurement of frailty in designing future clinical trials.’19
Based on this type of performance assessment recommendations for treatment based on performance status could be developed. For example, fit elderly patients (Karnofsky ≥80%/ Charlson index=0) might receive an alkylator-based combination such as MPT, VMP or cyclophosphamide- bortezomib-dexamethasone (CyBorD) or a non-alkylator-based combination of VTP, RVd or Rd until DP, but ay full doses. This patient group could be also candidates to receive high-dose chemotherapy followed by autologous stem cell transplantation. Patients who fall into the unfit category (Karnofsky 60%–80%, Charlson index ≤2) might be offered the same combinations as fit patients but with dose adjustments to enable optimal delivery of the different drugs, whereas frail patients may benefit from an alkylator-based combination such as CyTP, CyBorP, VMP lite or a non-alkylator-based combination such as Vp or Ld until DP, meaning that prednisone should be replaced by dexamethasone and cyclophosphamide by melphalan.
What else can be done to optimise therapy?
With a range of treatment options for elderly patients, clinicians have some ability to tailor therapy according to factors such as co-morbid conditions and the tolerability profile of the drugs offered. So VMP would be the preferred option in patients at high risk of thromboembolism. Patients with peripheral neuropathy may want to consider Rd, whereas VMP or MPT may
be the optimal choice for patients with renal failure. Lenalidomide could also be used at a reduced dosage. Frail patients over 75 years of age may benefit from lower doses of thalidomide (100mg or 50mg every other day), bortezomib (weekly schedule and subcutaneous administration) and lenalidomide (10–15mg or, in some cases, 5mg).20
Combination therapy based on novel agents, with or without alkylators, is the current standard of care for elderly MM patients. CR should be the main objective, but dose adjustments should be considered based on age and comorbidities to enable optimal delivery of effective therapy. There is a need for easy-to-administer geriatric scales and an evaluation of quality of life to help tailor therapy to individual patients. The good news is there are numerous planned and ongoing studies designed to address questions of optimal regimen, schedule, treatment duration and route of delivery. ●
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cancer-info/cancerstats/types/myeloma/ incidence/uk-multiple-myeloma-incidence- statistics (accessed 20 April 2015).
3. Hernández JM et al. Randomized comparison of dexamethasone combined with melphalan versus melphalan with prednisone in the treatment of elderly patients with multiple myeloma. Br J Haematol 2004;127(2):159–64.
4. Mateos M-V et al. Bortezomib, melphalan, and prednisone versus bortezomib, thalidomide, and prednisone as induction therapy followed by maintenance treatment with bortezomib and thalidomide versus bortezomib and prednisone in elderly patients with untreated multiple myeloma: a randomised trial. Lancet Oncol 2010;11(10):934–41.
5. 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.
6. Altekruse SF et al (eds). SEER Cancer Statistics Review, 1975–2007. Bethesda, MD: National Cancer Institute. http://seer.cancer.gov/
csr/1975_2007/ (based on November 2009 SEER data submission, posted to the SEER Website 2010).
7. Durie BG et al. Myeloma management guidelines: a consensus report from the
Scientific Advisors of the International Myeloma Foundation. Hematol J 2003;4(6):379–98.
8. Myeloma Trialists’ Collaborative Group. Combination chemotherapy versus melphalan plus prednisone as treatment for multiple myeloma: an overview of 6,633 patients from 27 randomized trials. J Clin Oncol 1998;16(12): 3832–42.
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(5):1239–47.
10. Palumbo A et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med 2012;366:1759–69.
11. Palumbo A et al. Second primary malignancies with lenalidomide therapy for newly diagnosed myeloma: a meta-analysis of individual patient data. Lancet Oncol 2014;15:333–42.
12. San Miguel JF et al. Persistent overall survival benefit and no increased risk of second malignancies with bortezomib-melphalan- prednisone versus melphalan-prednisone in patients with previously untreated multiple myeloma. J Clin Oncol 2013;31(4):448–55.
13. Mateos M-V et al. GEM2005 trial update comparing VMP/VTP as induction in elderly multiple myeloma patients: do we still need alkylators? Blood 2014;124(12):1887–93.
14. Ludwig H et al. Thalidomide-dexamethasone compared with melphalan-prednisolone in elderly patients with multiple myeloma. Blood 2009;113:3435–42.
15. Rajkumar SV et al. Lenalidomide plus high-dose dexamethasone versus lenalidomide plus low-dose dexamethasone as initial therapy for newly diagnosed multiple myeloma: an open-label randomised controlled trial. Lancet Oncol 2010;11(1):29–37.
16. Benboubker L et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med 2014;371:906–17.
17. Mateos M et al. Comparison of sequential vs alternating administration of bortezomib, melphalan, prednisone and lenalidomide plus dexamethasone in elderly patients with newly diagnosed multiple myeloma: GEM2010MAS65 trial. 2014 ASH Annual Meeting:abstract 178.
18. Gay F et al. Complete response correlates with long-term progression-free and overall survival in elderly myeloma treated with novel agents: analysis of 1175 patients. Blood 2011;117: 3025–31.
19. Palumbo A et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood 2015;125(13):2068–74.
20. Palumbo A, Gay F. How to treat elderly patients with multiple myeloma: combination of therapy or sequencing. Hematology Am Soc Hematol Educ Program 2009:566–77.
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