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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: firstname.lastname@example.org
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.
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
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