cyclophosphamide and dexamethasone (wCCd) in newly 2010;11(1):29–37. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms. melphalan, and prednisone versus bortezomib, thalidomide, In addition, considering efficacy and safety results of MP plus lenalidomide evaluated in the MM-015, one conclusion would be that melphalan or alkylators are not good partners for immunomodulatory drugs, but this affirmation does not apply to proteasome inhibitors, which are excellent partners for alkylators as it has been previously showed. Prophylactic fluconazole (to prevent candidiasis) and aciclovir (to prevent herpes simplex and/or zoster) are typically coprescribed with chemotherapy. The rationale for the approval was a randomized trial in which bendamustine plus prednisone (BP) was compared with MP. Novel agents are now commonly used in all age groups in myeloma. By accessing the work you hereby accept the Terms. [ 1] In women, five-year survival ranges from 74% to 26% in the same age groups. Stringent trial entry criteria typically exclude the majority of very elderly patients due to reduced performance status, comorbidities, or organ dysfunction.9 Trial candidates over the age of 80, therefore, tend to be unusually fit and are not representative of the typical very elderly patient. Bortezomib plus melphalan and prednisone for initial treatment of multiple myeloma. Frailty is a geriatric syndrome associated with reduced functional reserve, impairment in multiple physiological systems, and reduced ability to regain physiological homeostasis. Epub 2020 Apr 2. Life expectancy for multiple myeloma patients is largely dependent on the stage of cancer progression. Riccardi A, Mora O, Tinelli C, et al.

Bortezomib-based Regimens In the randomized phase III Velcade as Initial Standard Therapy in Multiple Myeloma (VISTA) trial, bortezomib plus MP (VMP) was compared with MP in a series of 682 newly diagnosed MM patients. If you are lucky enough to have a general practitioner who picks up high protein in the blood and finds the disease early while it is smoldering, or stage one, you have won the Myeloma Lottery. These were combined with patient age to categorize individuals into three groups: fit, intermediate fitness, and frail. The data do, however, allow some conclusions to be drawn to guide clinicians in the management of very elderly patients. Volume 2016:11 Pages 423—435, Editor who approved publication: Low-dose radiotherapy may be effective in the treatment of isolated painful bony lesions; typically, only a single dose (8 Gy) is required for adequate control.29 Kyphoplasty or vertebroplasty may help when vertebral compression fractures results in pain unresponsive to analgesia or to stabilize vertebrae at risk of fracture. Time-to-diagnosis and symptoms of myeloma, lymphomas and leukaemias: a report from the Haematological Malignancy Research Network. The Lancet Oncology. Pragmatically, the treating clinician should take into account age, performance status, a CGA tool, and importantly the views of the patient and their family when planning treatment. The above percentage of manuscripts have been rejected in the last 12 months. In those diagnosed with MGUS, most do not progress to myeloma: a paraprotein is found in 4%–5% of people in their 80s,10 whereas the incidence of myeloma in this group is only 40 per 100,000.11 It is therefore of fundamental importance to consider whether a patient has myeloma or incidental MGUS with unrelated organ dysfunction (Figure 2). Individualized Treatment Strategies for Non-transplant Candidate Patients The different novel treatment combinations offer physicians the possibility to tailor treatment approaches based on the individual patient profile and patient’s preference.

Lenalidomide and dexamethasone in transplant-ineligible Carfilzomib has been combined with lenalidomide plus low-dose dex (CRd) in a pilot phase I/II trial in newly diagnosed MM patients, including young and elderly patients.32 Results of a subanalysis of 23 elderly MM patients showed impressive efficacy (100 % of ORR, with stringent CR in 65 % of patients), and an acceptable toxicity profile (13 % of grade 1–2 PN). Nevertheless, in the current clinical practice, cyclophosphamide is being used because the suspicion of equivalent efficacy and better tolerability than melphalan. thalidomide to oral melphalan/prednisone in patients with Challenge 6 – the management of end-of-life care. There was no difference in treatment according to frailty group (p = 0.38). HHS First, aging is associated with organ dysfunction, poorer resilience to physiological stressors, reduced functional status, and an increasing burden of comorbidities.6 Second, the elderly are at increased risk of frailty, a poorly defined syndrome characterized by a state of increased vulnerability to minor stressors with cumulative deficits in multiple physiological systems, resulting in an increased risk of hospitalization, dependency, and reduced life expectancy. Carfilzomib, a novel proteasome inhibitor, is effective in newly diagnosed and relapsed myeloma.24,55 It is associated with a reduced toxicity compared to bortezomib (particularly PN) and may therefore take the place of bortezomib first line in the future, although its use should be avoided in patients with significant pre-existing cardiac disease. Elderly patients with multiple myeloma: towards a frailty approach? Targeting CD38 with daratumumab monotherapy in multiple myeloma. Bethesda, MD: National Cancer Institute; 2010. Google Analytics is used for user behavior tracking/reporting.

2013;31(4):448–455. Moreau P, Kolb B, Hulin C, et al., Carfilzomib plus melphalan Lenalidomide in combination with high-dose dexamethasone (Len/ Dex) demonstrated superiority over dexamethasone plus placebo in a randomized Southeast Oncology Group (SWOG) trial in newly diagnosed MM patients, including patients over 65 years of age.17 A randomized, open-label Eastern Cooperative Oncology Group (ECOG) study compared lenalidomide and high-dose dexamethasone (Len/Dex) with lenalidomide and low-dose dexamethasone (Len/dex) in newly diagnosed MM patients.18 The Len/Dex regimen was associated with a higher ORR than Len/dex (79 % versus 68 %; p=0.008) but the 1-year OS was superior for low-dose dexamethasone, without differences at 3 years (see Table 1). The most relevant AEs observed with this combination were neutropenia (36 % of grade 4), thrombocytopenia (13 % of grade 4), and infections (15 % of grade 4). Schaapveld M, Visser O, Siesling S, Schaar CG, Zweegman S, Vellenga E. Improved survival among younger but not among older patients with Multiple Myeloma in the Netherlands, a population-based study since 1989. The single factor that best predicted a reduced overall survival (OS) was age over 80 years (hazard ratio [HR]: 2.4). Glycosaminoglycans, apolipoprotein-E and serum amyloid P component comprise 10% of deposits, while amyloid fibrils formed by misfolded proteins comprise 90% of deposits. Waage A, Gimsing P, Fayers P, et al., Melphalan and prednisone in patients with previously untreated multiple Treatment of relapsed/refractory multiple myeloma. Doublet vs triplet lenalidomide-containing regimens in newly diagnosed myeloma patients, younger or older than 75 years: subgroup analysis of a phase III study. Salvage therapy with bortezomib and dexamethasone in elderly patients with relapsed/refractory multiple myeloma. Carfilzomib, cyclophosphamide, and dexamethasone in patients with newly diagnosed multiple myeloma: a multicenter, phase 2 study.  |  Palumbo A, Rajkumar SV, Dimopoulos MA, et al. As the population ages, the incidence of myeloma in the very elderly will increase. 2000;82(7):1254–1260. Diagnosis of a very elderly patient presenting insidiously with mild anemia, renal impairment, or bone pain, all of which can often be attributed to another etiology, requires detailed evaluation.

Multiple myeloma (MM) is an incurable plasma cell disease that comprises 1 % of all cancers and 10 % of hematologic malignancies. Zweegman S, Engelhardt M, Larocca A; EHA SWG on ‘Aging and Hematology’. NIH prednisone plus thalidomide in patients older than 75 years with •  Top, © Copyright 2020  •  Dove Press Ltd   Challenge 4 – How should fitter very elderly patients be treated with combination chemotherapy? Guidelines for the diagnosis and management of multiple myeloma 2011. Considering that VMP should not be abandoned as alkylator-based combination and Len/dex as a new alkylator-free regimen, a provocative trial has been conducted by the Spanish Group in which a “Total Therapy” was administered to elderly patients in an approach including VMP and Len/dex for 18 cycles in a sequential or alternating approach. 2008;22(2):414–423. Both schemes were identical in terms of efficacy and safety but, of note, 42 % of patients achieved CR. The median PFS was significantly longer with VMPT-VT than with VMP (37 months versus 27 months; HR 0.58; p<0.0001), resulting in a significant benefit to OS (61 % versus 51 % at 5 years, HR 0.70; p=0.01).30 Maintenance with VT was well tolerated: grade 3 or grade 4 hematologic AEs were reported by 3 % of patients, and grade 3 or grade 4 PN were found in 5 % of patients. In the multivariate analysis a higher risk of death was observed related to age [ HR 1,07 (95% CI 1,02-1,12) p 0,002], number of frailty criteria [HR 1,13 (95% CI 1 – 1,3) p 0,05] and ISS [HR 2,6 (95% CI 1,8 -3,8) p 0,001]. No randomized trials have compared both drugs so MP should be considered at the present time the backbone to which novel drugs have to be added to build new standardsof care based on alkylators. Anemia is one of the hallmark features of myeloma, present in 35% at diagnosis. A PET-CT requires a patient to move to and from a bed unaided; an important consideration in a very elderly patient. Particular care must be taken to minimize toxicities, reducing doses if required to allow continuation of treatment when appropriate. In patients with renal failure, thalidomide, bortezomib, and bendamustine can be administered at the full approved dose; lenalidomide requires adjustments of the starting dose based on the creatinine clearance. In view of this, many clinicians now use subcutaneous bortezomib due to evidence of reduced PN, increased speed of delivery, and equivalent efficacy.44. 2009;27:3664-70. Blood, 2014;124:63–9. myeloma: updated results of a randomized controlled trial, 2008;143(4):537–540. Use of comprehensive geriatric assessment in older cancer patients: recommendations from the task force on CGA of the International Society of Geriatric Oncology (SIOG).
Niesvizky et al. With an increased burden of comorbidities and a reduced resilience to treatment and its associated toxicities, the management of myeloma in this age group requires a different approach to that in younger patients to maximize both quality and length of life.Keywords: myeloma, elderly, diagnosis, treatment. In both situations, this can reduce the quality and length of life. Thalidomide for previously untreated elderly patients with multiple myeloma: meta-analysis of 1685 individual patient data from 6 randomized clinical trials. 2012;13(4):353–365. COVID-19 is an emerging, rapidly evolving situation. Niesvizky R, Flinn IW, Rifkin R, et al. The average is the median survival rate. untreated multiple myeloma: an open-label phase 1/2 study, bortezomib-thalidomide compared with bortezomib-melphalanprednisone This translates into a significantly longer PFS and OS and, of note, elderly patients receiving VMP and achieving CR and, moreover, immunophenotypic CR had 8-year PFS and OS of 5 % and 66 %, respectively.4. AK is funded by Wellcome Trust.
International staging system for multiple myeloma. Ixazomib, an investigational oral proteasome inhibitor (PI), in combination with lenalidomide and dexamethasone (IRd), significantly extends progression-free survival (PFS) for patients (Pts) with relapsed and/or refractory multiple myeloma (RRMM): the Ph.

Moreau P, Masszi T, Grzasko N, et al. Get the latest research from NIH: https://www.nih.gov/coronavirus. According to the results previously revealed, Len/dex is superior to MPT so this old standard should be used less often.

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