Abstract
The multiple myeloma (MM) non transplant eligible (NTE) population is growing in line with the aging of the population in Western countries. Historically, this population has been known for having a greater risk of treatment related toxicity, and therefore drug development was slow and rather oriented towards the improvement of safety profile than the optimization of disease control. However, NTE MM patients, at least for the fit/non frail patients in recent years, seemed to have benefited more from a less palliative care to improve the depth of response and then prolong survival. NTE MM being a quite heterogeneous population, there are still a number of groups of patients that are in need of more efficient therapy, avoiding unnecessary toxicity, particularly for the frail patients. The use of triplet regimen with a melphalan-prednisone (MP) backbone has long been the standard of care for NTE MM, often dedicated to non-frail patients. New standards of care, triplet, and even quadruplet combinations, are emerging on the basis of the MP backbone but also on the more recently approved lenalidomide-dexamethasone (Rd) backbone. These developments were largely possible in line with the development of antibody-based immunotherapies (IT) in MM. The objective to improve outcomes with an acceptable safety profile will see other key therapeutic developments such as the dropping of dexamethasone early in the disease course or various attempts to allow permanent treatment discontinuation with a prolonged disease control. In that context, it is possible that immunomonitoring, minimal residual disease (MRD), and genomic risk-adaptation will become key elements of the treatment decisions on triplet-based regimens.
Highlights
Multiple myeloma (MM) typically develops among elderly patients with a median age at diagnosis of 70 years old, with an increased incidence with age
The first recently approved lenalidomide-dexamethasone (Rd) based triplet regimen proposed was VRd based on the SWOG-S0777 trial (VRd versus Rd) [28]. It was a 2017 US phase III randomized, open label study that evaluated the VRd induction regimen administered in 21 days cycles with bortezomib twice-weekly intravenously (IV), lenalidomide 25 mg from day 1 to 14 plus 20 mg dexamethasone in newly diagnosed multiple myeloma (NDMM) without immediate autologous stem cell transplant (ASCT) planned, for 8 cycles followed by continuous Rd until progression
This study showed in Refractory MM setting (RRMM) that SC daratumumab at a flat dose of 1800 mg was not inferior to IV with a comparable safety profile
Summary
Multiple myeloma (MM) typically develops among elderly patients with a median age at diagnosis of 70 years old, with an increased incidence with age. The inferior outcome of elderly patients seems rather to be related to the frequency of frailty factors due to aging (comorbidities and polymedication, decreased physiological reserve, cognitive impairment) [5], all leading to an increased risk of treatment related toxicity. It is impossible for most elderly newly diagnosed multiple myeloma (NDMM) patients to undergo an intensive treatment like triplet induction regimen followed by autologous stem cell transplant (ASCT), the current standard of care for younger MM transplant eligible patients.
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