Advertisement

Concise review ‐ Treatment of multiple myeloma in the very elderly: How do novel agents fit in?

Published:August 26, 2016DOI:https://doi.org/10.1016/j.jgo.2016.08.001

      Abstract

      In the last decades, treatment of multiple myeloma (MM) has greatly improved due to the introduction of novel agents, including proteasome inhibitors (PI) and immunomodulatory agents (IMiDs). Given their generalized use at diagnosis and at relapse and their proven benefit for the large cohort of MM patients, it is of pivotal importance to also critically evaluate any benefit of these agents in very elderly (>75 years) and frail patients.
      This review gives an overview of the benefits and toxicities of the currently available treatments in very elderly MM patients with a focus on first-line treatment. In addition we discuss the role of geriatric assessment to optimize treatment efficacy in the more vulnerable cohort.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Geriatric Oncology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Kyle R.A.
        • Rajkumar S.V.
        Multiple myeloma.
        Blood. 2008; 111: 2962-2972
        • Palumbo A.
        • Anderson K.
        Multiple myeloma.
        N. Engl. J. Med. 2011; 364: 1046-1060
        • Stewart A.K.
        • Rajkumar S.V.
        • Dimopoulos M.A.
        • Masszi T.
        • Spicka I.
        • Oriol A.
        • et al.
        Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.
        N. Engl. J. Med. 2014; 372: 142-152
        • Dimopoulos M.A.
        • Moreau P.
        • Palumbo A.
        • Joshua D.
        • Pour L.
        • Hajek R.
        • et al.
        Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomized, phase 3, open-label, multicenter study.
        Lancet Oncol. 2016; 17: 27
        • Moreau P.
        • Masszi T.
        • Grzasko N.
        • Bahlis N.J.
        • Hansson M.
        • Pour L.
        • et al.
        Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma.
        N. Engl. J. Med. 2016; 374: 1621-1634
        • 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: 621-631
        • Lonial S.
        • Weiss B.M.
        • Usmani S.Z.
        • Singhal S.
        • Chari A.
        • Bahlis N.J.
        • et al.
        Daratumumab monotherapy in patients with treatment-refractory multiple myeloma (SIRIUS): an open-label, randomized, phase 2 trial.
        Lancet. 2016; 387: 1551
        • Kumar S.K.
        • Dispenzieri A.
        • Lacy M.Q.
        • Gertz M.A.
        • Buadi F.K.
        • Pandey S.
        • et al.
        Continued improvement in survival in multiple myeloma: changes in early mortality and outcomes in older patients.
        Leukemia. 2013; 28: 1122-1128
        • Pozzi S.
        • Marcheselli L.
        • Bari A.
        • Liardo E.V.
        • Marcheselli R.
        • Luminari S.
        • et al.
        Survival of multiple myeloma patients in the era of novel therapies confirms the improvement in patients younger than 75 years: a population-based analysis.
        Br. J. Haematol. 2013; 163: 40-46
        • Fried L.P.
        • Ferrucci L.
        • Darer J.
        • Williamson J.D.
        • Anderson G.
        Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care.
        J. Gerontol. A Biol. Sci. Med. Sci. 2004; 59: 255-263
        • Kim S.M.
        • Kim M.J.
        • Jung H.A.
        • Kim K.
        • Kim S.J.
        • Jang J.H.
        • et al.
        Comparison of the Freiburg and Charlson comorbidity indices in predicting overall survival in elderly patients with newly diagnosed multiple myeloma.
        Biomed Res Int. 2014; 2014: 437852
        • Bringhen S.
        • Mateos M.V.
        • Zweegman S.
        • Larocca A.
        • Falcone A.P.
        • 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: 980-987
        • Palumbo A.
        • Hajek R.
        • Delforge M.
        • Kropff M.
        • Petrucci M.T.
        • Catalano J.
        • et al.
        Continuous lenalidomide treatment for newly diagnosed multiple myeloma.
        N. Engl. J. Med. 2012; 366: 1759-1769
        • Palumbo A.
        • Bringhen S.
        • Ludwig H.
        • Dimopoulos M.A.
        • Bladé J.
        • Mateos M.V.
        • et al.
        Personalized therapy in multiple myeloma according to patient age and vulnerability: a report of the European Myeloma Network (EMN).
        Blood. 2011; 118: 4519-4529
        • Ludwig H.
        • Durie B.G.M.
        • Bolejack V.
        • Turesson I.
        • Kyle R.A.
        • Bladé J.
        • et al.
        Myeloma in patients younger than age 50 years presents with more favorable features and shows better survival: an analysis of 10 549 patients from the International Myeloma Working Group.
        Blood. 2008; 111: 4039-4047
        • Nilsson T.
        • Höglund M.
        • Lenhoff S.
        • Rylander L.
        • Turesson I.
        • Westin J.
        • et al.
        A pooled analysis of karyotypic patterns, breakpoints and imbalances in 783 cytogenetically abnormal multiple myelomas reveals frequently involved chromosome segments as well as significant age- and sex-related differences.
        Br. J. Haematol. 2003; 120: 960-969
        • Avet-Loiseau H.
        • Hulin C.
        • Campion L.
        • Rodon P.
        • Marit G.
        • Attal M.
        • et al.
        Chromosomal abnormalities are major prognostic factors in elderly patients with multiple myeloma: the intergroupe francophone du myélome experience.
        J. Clin. Oncol. 2013; 31: 2806-2809
        • Kaiser M.F.
        • Johnson D.C.
        • Wu P.
        • Walker B.A.
        • Brioli A.
        • Mirabella F.
        • et al.
        Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma.
        Blood. 2013; 122: 219-226
        • Zweegman S.
        • Palumbo A.
        • Bringhen S.
        • Sonneveld P.
        Age and aging in blood disorders: multiple myeloma.
        Haematologica. 2014; 99: 1133-1137
        • Lopez A.
        • Mateos M.V.
        • Oriol A.
        • Valero M.
        • Martinez J.
        • Lorenzo J.I.
        • 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: 64-69
        • Auner H.W.
        • Szydlo R.
        • Hoek J.
        • Goldschmidt H.
        • Stoppa A.M.
        • Morgan G.J.
        • 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. 2014; 50: 209-215
        • 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: 1376-1383
        • San Miguel J.F.
        • Schlag R.
        • Khuageva N.K.
        • Dimopoulos M.A.
        • Shpilberg O.
        • Kropff M.
        • et al.
        Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma.
        N. Engl. J. Med. 2008; 359: 906-917
        • San Miguel J.F.
        • Schlag R.
        • Khuageva N.K.
        • Dimopoulos M.A.
        • 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. 2012; 31: 448-455
        • 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 randomized, phase 3, non-inferiority study.
        Lancet Oncol. 2011; 12: 431-440
        • Mateos M.V.
        • Richardson P.G.
        • Schlag R.
        • Khuageva N.K.
        • Dimopoulos M.A.
        • Shpilberg O.
        • et al.
        Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial.
        J. Clin. Oncol. 2010; 28: 2259-2266
        • Delforge M.
        • Bladé J.
        • Dimopoulos M.A.
        • Facon T.
        • Kropff M.
        • Ludwig H.
        • et al.
        Treatment-related peripheral neuropathy in multiple myeloma: the challenge continues.
        Lancet Oncol. 2010; 11: 1086-1095
        • Fayers P.M.
        • Palumbo A.
        • Hulin C.
        • Waage A.
        • Wijermans P.
        • Beksac 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: 1239-1247
        • Hulin C.
        • Facon T.
        • Rodon P.
        • Pegourie B.
        • Benboubker L.
        • Doyen C.
        • et al.
        Efficacy of melphalan and prednisone plus thalidomide in patients older than 75 years with newly diagnosed multiple myeloma: IFM 01/01 trial.
        J. Clin. Oncol. 2009; 27: 3664-3670
        • Benboubker L.
        • Dimopoulos M.A.
        • Dispenzieri A.
        • Catalano J.
        • Belch A.R.
        • Cavo M.
        • et al.
        Lenalidomide and dexamethasone in transplant-ineligible patients with myeloma.
        N. Engl. J. Med. 2014; 371: 906-917
        • 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: 826-833
        • 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: 1102-1108
        • Maes H.
        • Delforge M.
        Optimizing quality of life in multiple myeloma patients: current options, challenges and recommendations.
        Expert. Rev. Hematol. 2015; 8: 355-366
        • Takamatsu H.
        • Honda S.
        • Miyamoto T.
        • Yokoyama K.
        • Hagiwara S.
        • Ito T.
        • et al.
        Changing trends in prognostic factors for patients with multiple myeloma after autologous stem cell transplantation during the immunomodulator drug/proteasome inhibitor era.
        Cancer Sci. 2015; 106: 179-185
        • Offidani M.
        • Corvatta L.
        • Polloni C.
        • Centurioni R.
        • Visani G.
        • Brunori M.
        • et al.
        Assessment of vulnerability measures and their effect on survival in a real-life population of multiple myeloma patients registered at Marche Region Multiple Myeloma Registry.
        Clin Lymphoma Myeloma Leuk. 2012; 12: 423-432
        • Charlson M.
        • Szatrowski T.P.
        • Peterson J.
        • Gold J.
        Validation of a combined comorbidity index.
        J. Clin. Epidemiol. 1994; 47: 1245-1251
        • 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: 541-551
        • Fried L.P.
        • Tangen C.M.
        • Walston J.
        • Newman A.B.
        • Hirsch C.
        • Gottdiener J.
        • et al.
        Frailty in older adults: evidence for a phenotype.
        J. Gerontol. A Biol. Sci. Med. Sci. 2001; 56: M146-M156
        • Slaets J.P.J.
        Vulnerability in the elderly: frailty.
        Med Clin North Am. 2006; 90: 593-601
        • Hamaker M.E.
        • Jonker J.M.
        • de Rooij S.E.
        • Vos A.G.
        • Smorenburg C.H.
        • van Munster B.C.
        Frailty screening methods for predicting outcome of a comprehensive geriatric assessment in elderly patients with cancer: a systematic review.
        Lancet Oncol. 2012; 13: e437-e444
        • Palumbo A.
        • Bringhen S.
        • Mateos M.V.
        • Larocca A.
        • Facon T.
        • Kumar S.K.
        • et al.
        Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group report.
        Blood. 2015; 125: 2068-2074
        • Kenis C.
        • Bron D.
        • Libert Y.
        • Decoster L.
        • Van Puyvelde K.
        • Scalliet P.
        • et al.
        Relevance of a systematic geriatric screening and assessment in older patients with cancer: results of a prospective multicentric study.
        Ann. Oncol. 2013; 24: 1306-1312