Comorbidities in patients with multiple myeloma
DOI:
https://doi.org/10.14739/2409-2932.2019.2.171245Keywords:
comorbidity, multiple myeloma, cardiovascular diseases, renal insufficiency, infections, proteasome inhibitor, immunomodulationAbstract
Most clinicians consider performance status and comorbidities rather than chronological age in determining prognosis and treatment. Significant advancements in the treatment of myeloma have occurred including routine use of proteasome inhibitors and immunomodulatory drugs; however, the impact of comorbidity on clinical outcomes has not been fully investigated.
Here, we performed a review of the literature utilizing PubMed search engines to identify all publications comparing influence of comorbidities on survival of patients with multiple myeloma.
Comorbidities of patients with multiple myeloma have been demonstrated to affect progression-free survival and overall survival. Infections pose the greatest risk of early death in these patients. Cardiovascular and renal impairment is a dreaded complication in multiple myeloma and has been associated with decreased progression-free survival and overall survival. Cardiovascular complications associated with proteasome inhibitors and immunomodulatory drugs are an important component in supportive care of patients with myeloma.
Conclusions. Comorbidity plays a critical role in the outcome of myeloma patients in terms of early mortality. The management of multiple myeloma patients with comorbidities is a challenge that should be addressed improving the measurement of comorbidity and the coordination of care.
References
Cowan, A. J., Allen, C., Barac, A., Basaleem, H., Bensenor, I., Curado, M. P., et al. (2018) Global Burden of Multiple Myeloma: A Systematic Analysis for the Global Burden of Disease Study2016. JAMA Oncol., 4(9), 1221–1227. doi: 10.1001/jamaoncol.2018.2128
De Stefano, V., Za, T., & Rossi, E. (2014) Venous thromboembolism in multiple myeloma. Semin. Thromb. Hemost., 40(3), 338–347. doi: 10.1055/s-0034-1370793
Gavriatopoulou, M., Musto, P., Caers, J., Merlini, G., Kastritis, E., van de Donk, N., et al. (2018) European myeloma network recommendations on diagnosis and management of patients with rare plasma cell dyscrasias. Leukemia.,32(9), 1883–1898. doi: 10.1038/s41375-018-0209-7
Cornell, R. F., & Kassim, A. A. (2016) Evolving paradigms in the treatment of relapsed/refractory multiple myeloma: increased options and increased complexity. Bone Marrow Transplant., 51(4), 479–91. doi: 10.1038/bmt.2015.307
Richardson, P. G., Barlogie, B., Berenson, J., Singhal, S., Jagannath, S., Irwin, D., et al. (2003) A phase 2 study of bortezomib in relapsed, refractory myeloma. N. Engl. J. Med., 348(26)., 2609–2617. doi: 10.1056/NEJMoa030288
Richardson, P. G., Sonneveld, P., Schuster, M. W., Irwin, D., Stadtmauer, E. A., Facon, T., et al. (2005) Bortezomib or high-dose dexamethasone for relapsed multiple myeloma Assessment of Proteasome Inhibition for Extending Remissions (APEX) Investigators. N. Engl. J. Med., 352(24), 2487–2498. doi: 10.1056/NEJMoa043445
Stewart, A. K., Rajkumar, S. V., Dimopoulos, M. A., Masszi, T., Špička, I., Oriol, A., et al. (2015) Carfilzomib, lenalidomide, and dexamethasone for relapsed multiple myeloma.N. Engl. J. Med., 372(2), 142–152. doi: 10.1056/NEJMoa1411321
Dimopoulos, M. A., Moreau, P., Palumbo, A., Joshua, D., Pour, L., Hájek, R., et al. (2016) 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.,Vol. 17(1), 27–38. doi: 10.1016/S1470-2045(15)00464-7
Moreau, P., Masszi, T., Grzasko, N., Bahlis Nizar, J., Hansson, M., et al. (2016) Oral ixazomib, lenalidomide, and dexamethasone for multiple myeloma. N. Engl. J. Med. 374, 1621–1634. doi: 10.1056/NEJMoa1516282
Richardson, P. G., Xie, W., Jagannath, S., Jakubowiak, A., Lonial, S., Raje, N. S., et al. (2014) A phase 2 trial of lenalidomide, bortezomib, and dexamethasone in patients with relapsed and relapsed/refractory myeloma. Blood., 123(10), 1461–1469. doi: 10.1182/blood-2013-07-517276
Rosenthal, A., Luthi, J., Belohlavek, M., Kortüm, K. M., Mookadam, F., Mayo, A., et al. (2016) Carfilzomib and the cardiorenal system in myeloma: an endothelial effect. Blood Cancer J., 6, e384. doi: 10.1038/bcj.2015.112
Dimopoulos, M. A., Roussou, M., Gavriatopoulou, M., Psimenou, E., Ziogas, D., Eleutherakis-Papaiakovou, E., et al. (2017) Cardiac and renal complications of carfilzomib in patients with multiple myeloma .Blood Adv., 1(7), 449–454. doi: 10.1182/bloodadvances.2016003269
Moreau, P., San Miguel, J., Ludwig, H., Schouten, H., Mohty, M., Dimopoulos, M., et al. (2013) Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann. Oncol., 24, Suppl 6, 133–137. doi: 10.1093/annonc/mdt297
Schaapveld, M., Visser, O., Siesling, S., Schaar, C. G., Zweegman, S., Vellenga, E., et al. (2010) Improved survival among younger but not among older patients with Multiple Myeloma in the Netherlands, a population-based study since 1989. Eur. J. Cancer., 46(1), 160–169. doi: 10.1016/j.ejca.2009.07.006
Fried, L. P., Ferrucci, L., Darer, J., Williamson, J., Anderson, G., et al. (2004) Untangling the concepts of disability, frailty, and comorbidity: implications for improved targeting and care. J. Gerontol. A. Biol. Sci. Med. Sci., 59(3), 255–263. doi: 10.1093/gerona/59.3.M255 •
Turesson, I., Velez, R., Kristinsson, S. Y., & Landgren, O. (2010) Patterns of multiple myeloma during the past 5 decades: stable incidence rates for all age groups in the population but rapidly changing age distribution in the clinic. Mayo Clin. Proc., 85(3), 225–230. doi: 10.4065/mcp.2009.0426
Zweegman, S., Palumbo, A., Bringhen, S., & Sonneveld, P. (2014) Age and aging in blood disorders: multiple myeloma. Haematologica., 99(7), 1133–1137. doi: 10.3324/haematol.2014.110296
Palumbo, A., Bringhen, S., Mateos, M., Larocca, A., Facon, T., Kumar, S. K., et al. (2015) Geriatric assessment predicts survival and toxicities in elderly myeloma patients: an International Myeloma Working Group. Blood., 125(13), 2068–2074. doi: 10.1182/blood-2014-12-615187
Altekruse, S. F., Kosary, C. L., Krapcho, M., Neyman, N., Aminou, R., & Waldron, W. (2010) SEER Cancer Statistics Review, 1975–2007. National Cancer Institute, Bethesda.
Bringhen, S., Mateos, M. V., Zweegman, S., Larocca, A., Falcone, A. P., Oriol, A., et al. (2013) Age and organ damage correlate with poor survival in myeloma patients: meta-analysis of 1435 individual patient data from 4 randomized trials. Haematologica., 98(6), 980–987. doi: 10.3324/haematol.2012.075051
Chng, W. J., Dispenzieri, A., Chim, C. S., Fonseca, R., Goldschmidt, H., Lentzsch, S., et al. (2014) IMWG consensus on risk stratification in multiple myeloma. Leukemia, 28(2), 269–277. doi: 10.1038/leu.2013.247
Kristinsson, S. Y., Pfeiffer, R. M., Bjorkholm, M., Goldin, L. R., Schulman, S., Blimark, C., et al. (2010) Arterial and venous thrombosis in monoclonal gammopathy of undetermined significance and multiple myeloma: a population‐based study. Blood., 115(24), 4991–4998. doi: 10.1182/blood-2009-11-252072
Gregersen, H., Vangsted, A., Abildgaard, N., Andersen, N. F., Pedersen, R. S., Frølund, U. C., et al. (2017) The impact of comorbidity on mortality in multiple myeloma: a Danish nationwide population-based study. Cancer Med., 6(7), 1807–1816. doi: 10.1002/cam4.1128
Oortgiesen, B. E., van Roon, E. N., Joosten, P., Kibbelaar, R. E., Storm, H., Hovenga, S., et al. (2017) The role of initial clinical presentation, comorbidity and treatment in multiple myeloma patients on survival: a detailed population-based cohort study. Pharmacol., 73(6), 771–778. doi: 10.1007/s00228-017-2227-1
Palumbo, A., Avet-Loiseau, H., Oliva, S., Lokhorst, H. M., Goldschmidt, H., Rosinol, L., et al. (2015) Revised International Staging System for Multiple Myeloma: A Report From International Myeloma Working Group. Clin Oncol., 33(26), 2863–2869. doi: 10.1200/JCO.2015.61.2267
Larocca, A., & Palumbo, A. (2015) How I treat fragile myeloma patients. Blood., 126(19), 2179–2185. doi: 10.1182/blood-2015-05-612960
Augustson, B. M., Begum, G., Dunn, J. A., Barth, N. J., Davies, F., Morgan, G., et al. (2005) Analysis of patients entered onto the United Kingdom Medical Research Council trials between 1980 and 2002‐Medical Research Council Adult Leukaemia Working Party. Early mortality after diagnosis of multiple myeloma. J Clin Oncol., 23(36), 9219–9226. doi: 10.1200/JCO.2005.03.2086
Kastritis, E., Terpos, E., Roussou, M., et al. (2013) Very early death (<2 months) In myeloma is associated with advanced age, poor performance status and reduced use of novel agents, while early death within 12 months Is associated with high risk features of both the disease and the patient. Blood (ASH Annual Meeting Abstracts),122.
Kumar, S. K., Dispenzieri, A., Lacy, M. Q., Gertz, M. A., Buadi, F. K., Pandey, S., et al. (2014) Continued improvement in survival in multiple myeloma: Changes in early mortality and outcomes in older patients. Leukemia., 28(5), 1122–1128. doi: 10.1038/leu.2013.313
Dimopoulos, M. A., Delimpasi, S., Katodritou, E., Vassou, A., Kyrtsonis, M. C., Repousis, P., et al. (2014) Significant improvement in the survival of patients with multiple myeloma presenting with severe renal impairment after the introduction of novel agents. Ann Oncol., 25(1), 195–200. doi: 10.1093/annonc/mdt483
Holmström, M. O., Gimsing, P., Abildgaard, N., Andersen, N. F., Helleberg, C., Clausen, N. A., et al. (2015) Causes of early death in multiple myeloma patients who are ineligible for high‐dose therapy with hematopoietic stem cell support: A study based on the nationwide Danish Myeloma Database. Am J Hematol., 90(4), 73-74. doi: 10.1002/ajh.23932
O'Donnell, E. K., Kabrt, J., Ezenwajiaku, N., Yee, A. J., Horick, N., & Raje, N. S. (2015) Early mortality in newly diagnosed multiple myeloma in the context of novel drugs. Blood (ASH Annual Meeting Abstracts).,126.
Hsu, P., Lin, T. W., Gau, J. P., Yu, Y. B., Hsiao, L. T., Tzeng, C. H., et al. (2015) Risk of early mortality in patients with newly diagnosed multiple myeloma., Medicine., 94(50), 1–7. doi: 10.1097/MD.0000000000002305
Gonsalves, W. I., Godby, K., Kumar, S. K., & Costa, L. J. (2016) Limiting early mortality: Do's and don'ts in the management of patients with newly diagnosed multiple myeloma. Am J Hematol., 91(1), 101–108. doi: 10.1002/ajh.24129
Ríos-Tamayo, R., Sáinz, J., Martínez-López, J., Puerta, J. M., Chang, D. Y., Rodríguez, T., et al. (2016) Early mortality in multiple myeloma: the time-dependent impact of comorbidity: A population-based study in 621 real-life patients. Am J Hematol., 91(7), 700–704. doi: 10.1002/ajh.24389
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