Multiple myeloma is a disease typical of the elderly, and, because of the increase in life expectancy of the general population, its incidence is expected to grow in the future. Elderly patients represent a particular challenge due to their marked heterogeneity. Many new and highly effective drugs have been introduced in the last few years and results from clinical trials are promising. Besides the availability of novel agents, a careful evaluation of elderly patients showed to be a key factor for the success of therapy. A geriatric assessment is a valid strategy to better stratify patients. In particular, different scores are available today to appropriately assess elderly patients and define their fitness/frailty status. The choice of treatment—transplantation, triplets, doublets, or reduced-dose therapies including novel agents—should depend on the patient’s fitness status (fit, intermediate-fit or frail). Second-generation novel agents have also been evaluated as salvage therapy in the elderly, and these new agents certainly represent a further step forward in the treatment armamentarium for elderly patients with multiple myeloma.
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Cancer Research UK. Cancer Statistics for the UK. 2014.http://www.cancerresearchuk.org/health-professional/cancer-statistics-for-the-uk#heading-Zero (accessed 12 Jan 2018).
United Nations [UN]. Ageing. http://www.un.org/en/sections/issues-depth/ageing/ (accessed 12 Jan 2018).
van de Donk NWCJ, Lokhorst HM. New developments in the management and treatment of newly diagnosed and relapsed/refractory multiple myeloma patients. Expert Opin Pharmacother. 2013;14:1569–73.
Kumar SK, Dispenzieri A, Lacy MQ, Gertz MA, Buadi FK, Pandey S, et al. Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients. Leukemia. 2014;28:1122–8.
Panitsas F, Kothari J, Vallance G, Djebbari F, Ferguson L, Sultanova M, et al. Treat or palliate: outcomes of very elderly myeloma patients. Haematologica. 2018;103:e32–4.
Hulin C, Rodon P, Campion L, Roussel M, Leleu X, Marit G, et al. Clinical characteristics, chromosomal abnormalities and outcomes in very elderly patients with multiple myeloma: the IFM experience. Blood. 2012;120:Abstract204[ASH 2012].
Guyatt GH, Oxman AD, Kunz R, Falck-Ytter Y, Vist GE, Liberati A, et al. Rating quality of evidence and strength of recommendations: GRADE: going from evidence to recommendations. Br Med J. 2008;336:1049–51.
Palumbo A, Waage A, Hulin C, Beksac M, Zweegman S, Gay F, et al. Safety of thalidomide in newly diagnosed elderly myeloma patients: a meta-analysis of data from individual patients in six randomized trials. Haematologica. 2013;98:87–94.
Fayers PM, Palumbo A, Hulin C, Waage A, Wijermans P, Beksaç M, 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.
San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, et al. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. N Engl J Med. 2008;359:906–17.
San Miguel JF, Schlag R, Khuageva NK, Dimopoulos MA, Shpilberg O, Kropff M, 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;31:448–55.
Bringhen S, Larocca A, Rossi D, Cavalli M, Genuardi M, Ria R, et al. Efficacy and safety of once-weekly bortezomib in multiple myeloma patients. Blood. 2010;116:4745–53.
Moreau P, Pylypenko H, Grosicki S, Karamanesht I, Leleu X, Grishunina M, 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.
Benboubker L, Dimopoulos MA, Dispenzieri A, Catalano J, Belch AR, Cavo M, et al. Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma. N Engl J Med. 2014;371:906–17.
Mateos M-V, Martínez-López J, Hernández M-T, Ocio E-M, Rosiñol L, Martínez R, et al. Sequential vs alternating administration of VMP and Rd in elderly patients with newly diagnosed MM. Blood. 2016;127:420–25.
Facon T, Lee JH, Moreau P, Niesvizky R, Dimopoulos MA, Hajek R et al. Phase 3 study (CLARION) of carfilzomib, melphalan, prednisone (KMP) v bortezomib, melphalan, prednisone (VMP) in newly diagnosed multiple myeloma (NDMM). In: International Myeloma Workshop. 2017, p abstract OP-044; e37–8.
Durie BGM, Hoering A, Abidi MH, Rajkumar SV, Epstein J, Kahanic SP, et al. Bortezomib with lenalidomide and dexamethasone versus lenalidomide and dexamethasone alone in patients with newly diagnosed myeloma without intent for immediate autologous stem-cell transplant (SWOG S0777): a randomised, open-label, phase 3 trial. Lancet. 2017;389:519–27.
Mateos M-V, Dimopoulos MA, Cavo M, Suzuki K, Jakubowiak A, Knop S, et al. Daratumumab plus Bortezomib, Melphalan, and Prednisone for Untreated Myeloma. N Engl J Med. 2017;378:518–28.
Palumbo A, Hajek R, Delforge M, Kropff M, Petrucci MT, Catalano J, et al. Continuous lenalidomide treatment for newly diagnosed multiple myeloma. N Engl J Med. 2012;366:1759–69.
Zweegman S, van der Holt B, Mellqvist U-H, Salomo M, Bos GMJ, Levin M-D, et al. Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood. 2016;127:1109–16.
Stewart AK, Jacobus S, Fonseca R, Weiss M, Callander NS, Chanan-Khan AA, et al. Melphalan, prednisone, and thalidomide vs melphalan, prednisone, and lenalidomide (ECOG E1A06) in untreated multiple myeloma. Blood. 2015;126:1294–301.
Delforge M, Minuk L, Eisenmann J-C, Arnulf B, Canepa L, Fragasso A, et al. Health-related quality-of-life in patients with newly diagnosed multiple myeloma in the FIRST trial: lenalidomide plus low-dose dexamethasone versus melphalan, prednisone, thalidomide. Haematologica. 2015;100:826–33.
Facon T, Dimopoulos MA, Dispenzieri A, Catalano JV, Belch A, Cavo M et al. Final analysis of survival outcomes in the randomized phase 3 FIRST trial. Blood. 2018;131:301-310.
Hulin C, Belch A, Shustik C, Petrucci MT, Dührsen U, Lu J, et al. Updated outcomes and impact of age with lenalidomide and low-dose dexamethasone or melphalan, prednisone, and thalidomide in the randomized, phase III FIRST trial. J Clin Oncol. 2016;34:3609–17.
Jackson G, Davies FE, Pawlyn C, Cairns D, Striha A, Hockaday A et al. Lenalidomide maintenance significantly improves outcomes compared to observation irrespective of cytogenetic risk: results of the myeloma XI Trial. In: ASH 59th Annual Meeting & Exposition. 2017, p Abstract #436.
Palumbo A, Bringhen S, Larocca A, Rossi D, Di Raimondo F, Magarotto V, 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.
Mateos M-V, Oriol A, Martínez-López J, Gutiérrez N, Teruel A-I, de Paz R, 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;11:934–41.
Tucci A, Ferrari S, Bottelli C, Borlenghi E, Drera M, Rossi G. A comprehensive geriatric assessment is more effective than clinical judgment to identify elderly diffuse large cell lymphoma patients who benefit from aggressive therapy. Cancer. 2009;115:4547–53.
Extermann M, Hurria A. Comprehensive geriatric assessment for older patients with cancer. J Clin Oncol. 2007;25:1824–31.
Pallis AG, Wedding U, Lacombe D, Soubeyran P, Wildiers H. Questionnaires and instruments for a multidimensional assessment of the older cancer patient: What clinicians need to know? Eur J Cancer. 2010;46:1019–25.
Palumbo A, Bringhen S, Mateos M-V, Larocca A, Facon T, Kumar SK, et al. Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report. Blood. 2015;125:2068–74.
Engelhardt M, Dold SM, Ihorst G, Zober A, Möller M, Reinhardt H, et al. Geriatric assessment in multiple myeloma patients: validation of the International Myeloma Working Group (IMWG) score and comparison with other common comorbidity scores. Haematologica. 2016;101:1110–19.
Facon T, Hulin C, Dimopoulos MA, Belch A, Meuleman N, Mohty M et al. A Frailty Scale Predicts Outcomes of Patients with Newly Diagnosed Multiple Myeloma Who Are Ineligible for Transplant Treated with Continuous Lenalidomide Plus Low-Dose Dexamethasone on the FirstTrial. 2015. Abstract #4239 [ASH 2015 57th Meeting].
Milani P, Vincent Rajkumar S, Merlini G, Kumar S, Gertz MA, Palladini G, et al. N-terminal fragment of the type-B natriuretic peptide (NT-proBNP) contributes to a simple new frailty score in patients with newly diagnosed multiple myeloma. Am J Hematol. 2016;91:1129–34.
Takeoka Y, Sakatoku K, Miura A, Yamamura R, Araki T, Seura H, et al. Prognostic Effect of Low Subcutaneous Adipose Tissue on Survival Outcome in Patients With Multiple Myeloma. Clin Lymphoma Myeloma Leuk. 2016;16:434–41.
Zweegman S, Levin M-D, Klein SK, de Waal EGM, Eeltink CM, Ypma PF et al. Feasibility and efficacy of dose adjusted melphalan–prednisone–bortezomib (MPV) in patients ≥ 75 years with newly diagnosed multiple myeloma; preliminary results of the phase II HOVON 123 study. In: 22th European Hematology Association [EHA] Annual Congress. EHA Learning Center: Madrid (ES), 2017, p Abstract P340.
Sonneveld P, Avet-Loiseau H, Lonial S, Usmani S, Siegel D, Anderson KC, et al. Treatment of multiple myeloma with high-risk cytogenetics: a consensus of the International Myeloma Working Group. Blood. 2016;127:2955–62.
Gay F, Engelhardt M, Terpos E, Wäsch R, Giaccone L, Auner HW et al. From transplant to novel cellular therapies in multiple myeloma: EMN guidelines and future perspectives. Haematologica. 2018;103:197-211.
Auner HW, Szydlo R, Hoek J, Goldschmidt H, Stoppa AM, Morgan GJ, et al. Trends in autologous hematopoietic cell transplantation for multiple myeloma in Europe: increased use and improved outcomes in elderly patients in recent years. Bone Marrow Transplant. 2015;50:209–15.
Merz M, Jansen L, Castro FA, Hillengass J, Salwender H, Weisel K, et al. Survival of elderly patients with multiple myeloma—Effect of upfront autologous stem cell transplantation. Eur J Cancer. 2016;62:1–8.
Merz M, Neben K, Raab MS, Sauer S, Egerer G, Hundemer M, et al. Autologous stem cell transplantation for elderly patients with newly diagnosed multiple myeloma in the era of novel agents. Ann Oncol. 2014;25:189–95.
Auner HW, Iacobelli S, Sbianchi G, Knol-Bout C, Blaise D, Russell NH et al. Melphalan 140 mg/m2 or 200 mg/m2 for autologous transplantation in myeloma: results from the collaboration to collect autologous transplant outcomes in lymphoma and myeloma (CALM) study. A Report by the EBMT Chronic Malignancies Working Party. Haematologica. 2017. haematol.2017.181339.
Straka C, Liebisch P, Salwender H, Hennemann B, Metzner B, Knop S, et al. Autotransplant with and without induction chemotherapy in older multiple myeloma patients: long-term outcome of a randomized trial. Haematologica. 2016;101:1398–406.
Garderet L, Beohou E, Caillot D, Stoppa AM, Touzeau C, Chretien ML, et al. Upfront autologous stem cell transplantation for newly diagnosed elderly multiple myeloma patients: a prospective multicenter study. Haematologica. 2016;101:1390–97.
Engelhardt M, Ihorst G, Caers J, Günther A, Wäsch R. Autotransplants in older multiple myeloma patients: hype or hope in the era of novel agents? Haematologica. 2016;101:1276–8.
Kleber M, Ihorst G, Terhorst M, Koch B, Deschler B, Wäsch R, et al. Comorbidity as a prognostic variable in multiple myeloma: comparative evaluation of common comorbidity scores and use of a novel MM–comorbidity score. Blood Cancer J. 2011;1:e35–e35.
Kleber M, Ihorst G, Groß B, Koch B, Reinhardt H, Wäsch R, et al. Validation of the Freiburg comorbidity index in 466 multiple myeloma patients and combination with the international staging system are highly predictive for outcome. Clin Lymphoma Myeloma Leuk. 2013;13:541–51.
Engelhardt M, Domm A-S, Dold SM, Ihorst G, Reinhardt H, Zober A, et al. A concise revised myeloma comorbidity Index as a valid prognostic instrument in a large cohort of 801 multiple myeloma patients. Haematologica. 2017;102:910–21. haematol.2016.162693
Saad A, Mahindra A, Zhang M-J, Zhong X, Costa LJ, Dispenzieri A, et al. Hematopoietic cell transplant comorbidity index is predictive of survival after autologous hematopoietic cell transplantation in multiple myeloma. Biol Blood Marrow Transplant. 2014;20:402–8.e1.
Straka C, Schäfer-Eckart K, Bassermann F, Hertenstein B, Engelhardt M, Salwender H, et al. Prospective randomized trial of Len/Dex induction followed by tandem MEL140 with autologous blood stem cell transplantation and len maintenance versus continued therapy with Len/Dex in myeloma patients age 60–75 years: protocol-defined safety analysis Af…. Blood. 2012;120:Abstract[ASH 2012].
Gay F, Magarotto V, Crippa C, Pescosta N, Guglielmelli T, Cavallo F, et al. Bortezomib induction, reduced-intensity transplantation, and lenalidomide consolidation-maintenance for myeloma: updated results. Blood. 2013;122:1376–83.
Gay F, Larocca A, Wijermans P, Cavallo F, Rossi D, Schaafsma R, 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.
Paiva B, Martinez-Lopez J, Vidriales M-B, Mateos M-V, Montalban M-A, Fernandez-Redondo E, et al. Comparison of immunofixation, serum free light chain, and immunophenotyping for response evaluation and prognostication in multiple myeloma. J Clin Oncol. 2011;29:1627–33.
Bringhen S, Mateos MV, Zweegman S, Larocca A, Falcone AP, Oriol A, et al. Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials. Haematologica. 2013;98:980–87.
Ludwig H, Delforge M, Facon T, Einsele H, Gay F, Moreau P et al. Prevention and management of adverse events of Novel agents in multiple myeloma: A consensus of the european myeloma network. Leukemia. 2017 Dec 18. doi: 10.1038/leu.2017.353. [Epub ahead of print].
Magarotto V, Bringhen S, Offidani M, Benevolo G, Patriarca F, Mina R, et al. Triplet vs doublet lenalidomide-containing regimens for the treatment of elderly patients with newly diagnosed multiple myeloma. Blood. 2016;127:1102–8.
Niesvizky R, Flinn IW, Rifkin R, Gabrail N, Charu V, Clowney B, et al. Community-based phase IIIB trial of three UPFRONT bortezomib-based myeloma regimens. J Clin Oncol. 2015;33:3921–9.
Bringhen S, Offidani M, Musto P, Liberati AM, Benevolo G, Cascavilla N et al. Long term outcome of lenalidomide-dexamethasone (Rd) vs melphalan-lenalidomide-prednisone (MPR) vs cyclophosphamide-prednisone-lenalidomide (CPR) as induction followed by lenalidomide-prednisone (RP) Vs lenalidomide (R) as maintenance in a community-based. In: ASH 59th Annual Meeting and Exposition. Atlanta, GA, 2017, p Abstract #901.
Cid Ruzafa J, Merinopoulou E, Baggaley RF, Leighton P, Werther W, Felici D, et al. Patient population with multiple myeloma and transitions across different lines of therapy in the USA: an epidemiologic model. Pharmacoepidemiol Drug Saf. 2016;25:871–9.
Lopez A, Mateos M-V, Oriol A, Valero M, Martínez J, Lorenzo JI, et al. Patterns of relapse and outcome of elderly multiple myeloma patients treated as front-line therapy with novel agents combinations. Leuk Res Rep. 2015;4:64–9.
Dimopoulos MA, Moreau P, Palumbo A, Joshua D, Pour L, Hájek R, et al. Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol. 2016;17:27–38.
Stewart AK, Rajkumar SV, Dimopoulos MA, Masszi T, Špička I, Oriol A, et al. Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma. N Engl J Med. 2015;372:142–52.
Dimopoulos MA, Stewart AK, Masszi T, Špička I, Oriol A, Hájek R, et al. Carfilzomib, lenalidomide, and dexamethasone in patients with relapsed multiple myeloma categorised by age: secondary analysis from the phase 3 ASPIRE study. Br J Haematol. 2017;177:404–13.
Moreau P, Masszi T, Grzasko N, Bahlis NJ, Hansson M, Pour L, et al. Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;374:1621–34.
Lokhorst HM, Plesner T, Laubach JP, Nahi H, Gimsing P, Hansson M, et al. Targeting CD38 with daratumumab monotherapy in multiple myeloma. N Engl J Med. 2015;373:1207–19.
Lonial S, Weiss BM, Usmani SZ, Singhal S, Chari A, Bahlis NJ, et al. Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomised, phase 2 trial. Lancet. 2016;387:1551–60.
Dimopoulos MA, Oriol A, Nahi H, San-Miguel J, Bahlis NJ, Usmani SZ, et al. Daratumumab, lenalidomide, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:1319–31.
Palumbo A, Chanan-Khan A, Weisel K, Nooka AK, Masszi T, Beksac M, et al. Daratumumab, bortezomib, and dexamethasone for multiple myeloma. N Engl J Med. 2016;375:754–66.
Chari A, Suvannasankha A, Fay JW, Arnulf B, Kaufman JL, Ifthikharuddin JJ, et al. Daratumumab plus pomalidomide and dexamethasone in relapsed and/or refractory multiple myeloma. Blood. 2017;130:974–81.
San Miguel J, Weisel K, Moreau P, Lacy M, Song K, Delforge M, et al. Pomalidomide plus low-dose dexamethasone versus high-dose dexamethasone alone for patients with relapsed and refractory multiple myeloma (MM-003): a randomised, open-label, phase 3 trial. Lancet Oncol. 2013;14:1055–66.
Lonial S, Dimopoulos M, Palumbo A, White D, Grosicki S, Spicka I, et al. Elotuzumab therapy for relapsed or refractory multiple myeloma. N Engl J Med. 2015;373:621–31.
Jakubowiak A, Offidani M, Pégourie B, De La Rubia J, Garderet L, Laribi K, et al. Randomized phase 2 study: elotuzumab plus bortezomib/dexamethasone vs bortezomib/dexamethasone for relapsed/refractory MM. Blood. 2016;127:2833–40.
Baz RC, Martin TG, Lin H-Y, Zhao X, Shain KH, Cho HJ, et al. Randomized multicenter phase 2 study of pomalidomide, cyclophosphamide, and dexamethasone in relapsed refractory myeloma. Blood. 2016;127:2561–8.
Richardson PG, San Miguel JF, Moreau P, Hajek R, Dimopoulos MA, Palumbo A et al. Real-World and clinical trial data in relapsed/refractory multiple myeloma (RRMM): evaluating treatment duration and comparing effectiveness and efficacy. In: 59th American Society of Hematology [ASH] Annual Meeting and Exposition. Atlanta (US-GA), 2017, p Abstract 3149.
Engelhardt M, Selder R, Pandurevic M, Möller M, Ihorst G, Waldschmidt J, et al. Multidisciplinary tumor boards: facts and satisfaction analysis of an indispensable comprehensive Cancer Center Instrument. Dtsch Med Wochenschr. 2017;142:e51–e60.
The expert panel thanks all the investigators of the EMN group in the different countries for their support. This work is supported by the Deutsche Krebshilfe (grants 1095969 and 111424 to ME and RW). HWA acknowledges the support of the Imperial College London National Institute of Health Research-Biomedical Research Centre (NIHR-BRC).
Conflict of interest
AL has received honoraria from Amgen, BMS, Celgene, and Janssen-Cilag; ET has received honoraria from Amgen, Celgene, Genesis, Janssen, Novartis, Takeda, Abbvie, BMS, and GSK; research funding from Celgene, Janssen, Amgen; has participated in DMC for Celgene and in SC for Amgen, Takeda and Janssen; HG has received research support from Amgen, BMS, Celgene, Chugai, Janssen, Sanofi, Mundipharma, Takeda, Novartis, honoraria from Celgene, Janssen, Novartis, Chugai, BMS, ArtTempi, and served on the advisory boards of Adaptive Biotechnology, Amgen, BMS, Celgene, Janssen, Sanofi, Takeda; FG has participated in the advisory board of Takeda, Seattle Genetics, Mundipharma, Janssen, and received honoraria from Takeda, Amgen, Celgene, Janssen, BMS; SB has received honoraria from BMS, Celgene, Janssen-Cilag, and participated in the advisory board of Amgen, Mundipharma, Karyopharm; JC has participated in the advisory board of and received honoraria from Amgen, Celgene, Janssen and research funding from Celgene. MO has received honoraria from and participated in advisory board of Celgene, Janssen, Takeda, Amgen, BMS; HWA has received research support from Amgen, participated in the advisory board of and honoraria from Amgen, Takeda, Karyopharm, Chugai, Novartis; HE has received honoraria, research support from and served on the advisory board of Janssen, Celgene, Amgen, BMS, Novartis; MB has received honoraria from Sanofi, Celgene, Amgen, Janssen, Novartis, Abbvie, BMS, and research funding from Celgene, Janssen, Amgen, BMS, Mundipharma, Novartis, Sanofi; PS has participated in the advisory board of and received honoraria from Amgen, Celgene, Janssen, Karyopharm, Takeda-Millennium, and research support from Amgen, Celgene, Janssen, Takeda-Millennium, SkylineDx.
This manuscript is published as a consensus paper by the European Hematology Association and the European Myeloma Network.
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