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Oncology & Hematology Review (US) Highlights How Should We Treat Elderly Newly Diagnosed Multiple Myeloma Patients? María-Victoria Mateos, MD, PhD Consultant Physician, Hospital Universitario de Salamanca-Instituto de Investigación Biomédica de Salamanca (IBSAL), Salamanca, Spain Abstract Multiple myeloma is the second most frequent hematologic disease, which usually affects patients over 65 years of age. Treatment goals for these non-transplant-eligible patients should be to prolong survival by achieving the best response, while ensuring quality of life. Melphalan plus prednisone has been the classic backbone to which proteasome inhibitors and immunomodulatory drugs were added and, recently, lenalidomide plus low-dose dexamethasone emerged as a new standard of care, free of alkylator, and also as a backbone to which second-generation proteasome inhibitors are being added. Monoclonal antibodies will take part of these treatments regimens in the future. Prolonged treatment in elderly patients also improves the quality and duration of clinical responses, extending time to progression and progression-free survival; however, the optimal scheme, appropriate doses, and duration of long-term therapy have not yet been fully determined. Finally, elderly patients under treatment require close monitoring and individualized, dose-modified regimens to improve tolerability and treatment efficacy, while maintaining their quality of life. Keywords Multiple myeloma, elderly patients, new agents, new diagnosis Disclosure: María-Victoria Mateos, MD, PhD, has received honoraria for lectures or participation in advisory boards of Amgen, Celgene, Janssen, Onyx, and Takeda. No funding was received in the publication of this article. Open Access: This article is published under the Creative Commons Attribution Noncommercial License, which permits any noncommercial use, distribution, adaptation, and reproduction provided the original author(s) and source are given appropriate credit. Received: January 19, 2015 Accepted: February 10, 2015 Citation: Oncology & Hematology Review, 2015;11(1):43–9 Correspondence: María-Victoria Mateos, MD, PhD, Hospital Universitario de Salamanca, Paseo San Vicente 58-182, 37007, Salamanca, Spain. E: mvmateos@usal.es Multiple myeloma (MM) is an incurable plasma cell disease that comprises 1  % of all cancers and 10  % of hematologic malignancies. It primarily affects older individuals—the median age at the moment of diagnosis is 70 years—and two-thirds of multiple myeloma patients are over 65 years of age when they are first diagnosed. The outcome of MM patients has significantly improved in the last decade. 1,2 However, the main benefit has accrued to young patients, due to the introduction of high-dose therapy followed by autologous stem cell transplantation (HDT-ASCT) that are upfront and novel agents as rescue therapy, while only a marginal change has been observed in patients older than 65 years. However, the availability of new frontline treatment regimens based on the novel agents thalidomide, bortezomib, and lenalidomide has extended the options for transplant-ineligible MM patients. In parallel with the advances in treatment options, goals of therapy have also evolved for non-transplant candidate patients. While prolongation of disease-free and overall survival remain the ultimate goal, to achieve prolonged treatment-free intervals and good quality of life also become important aims. Moreover, in the era of melphalan plus prednisone (MP), the goal was to achieve partial response (PR); by contrast, nowadays with the new agents, complete response (CR) has become the new goal also in elderly patients. Thus, in a retrospective analysis on pooled data of 1,175 patients with newly diagnosed MM, treated with MP and novel agents, the achievement of CR was associated with improved progression-free survival (PFS) and overall survival (OS): the 3-year PFS was 67 % in patients who achieved CR versus 27 % in those in very good 50 PR (VGPR) or PR, whereas the 3-year OS rates were 91  % in patients who obtained CR and 67 % to 70 % in those in VGPR or PR. 3 Moreover, upon using more sensitive parameters, such as free-light chain and multiparameter flow cytometry, to define the depth of response, a Spanish group has shown, in a prospective analysis conducted in elderly patients receiving novel agents, that to achieve immunophenotypic response translated into superior PFS and OS compared with the presence of minimal residual disease after induction. 4 Therefore, to monitor treatment efficacy with highly sensitive techniques should also be an objective in the treatment of elderly patients, since this could help clinicians to define the optimal level of response and to individualize treatment intensity and duration, with an appropriate balance with toxicity. This review will provide a summary of data supporting the current management of elderly patients with newly diagnosed MM. The second generation of novel agents will be also evaluated. The potential role of maintenance/continuous treatment, as well as how to choose the best option of therapy for an optimized disease control, are also discussed. Induction Regimens Classic Combinations Melphalan was the first active alkylating agent used for the treatment of MM patients, and MP was the standard of care for over 30 years, although it yielded only PR in 40–60 % of patients, with <5 % of CRs, and a PFS Tou c h ME d ica l ME d ia