Each of these assessments, whether through a survey, risk assessment profile, or clinical visit, is intended to screen and evaluate for frailty.
In contrast, the median OS was worse in patients age 80 and older (41 vs. 55 and 56 months for the two younger age groups, respectively).

Health-related quality of life in multiple myeloma patients receiving high-dose chemotherapy with autologous blood stem-cell support. In the three-arm randomized IFM trial 99606 for patients aged 65 to 75 years, the above regimen yielded a higher response rate and CR rate than MP, but PFS and OS were not significantly better; moreover, the MPT regimen was significantly superior both to MP and to melphalan plus ASCT. Ongoing HRQL assessment is important to balance efficacy and toxicity, especially in elderly, frail patients.

If nonmyelosuppressive agents by themselves are inadequate, alternating myelosuppressive and nonmyelosuppressive approaches should be considered in patients who cannot sustain the pace of therapy because of myelosuppression. Dimopoulos MA, Stewart AK, Masszi T, Špička I, Oriol A, Hájek R, Rosiñol L, Siegel D, Mihaylov GG, Goranova-Marinova V, Rajnics P, Suvorov A, Niesvizky R, Jakubowiak A, San-Miguel J, Ludwig H, Palumbo A, Obreja M, Aggarwal S, Moreau P. Br J Haematol. Kyle RA, Rernstein ED, Therneau TM, et al. 21. The transplantation pathway is used more frequently in younger patients and the nontransplantation pathway in older. Bortezomib-based regimens are preferred in patients with renal failure or a previous episode of deep vein thrombosis. Harousseau J-L, Attal M, Avet-Loiseau H. The role of complete remission in multiple myeloma. 27. The objective of these improved treatment regimens should be to achieve complete response, as in younger patients. Mateos MV, Richardson PG, Schlag R, et al. None of the preferences suggested contradicts alternative options that can be used subsequently. How to treat elderly patients with multiple myeloma in 2020? Longer term follow up of the randomized phase III Trial SWOG S0777: bortezomib, lenalidomide and dexamethasone vs. lenalidomide and dexamethasone in patients (pts) with previously untreated multiple myeloma without an intent for immediate autologous stem transplant. Barlogie B, van Rhee F, Shaughnessy JD Jr, et al. Whether modifying treatment according to frailty improves outcomes is not yet known, but it is clearly worth exploring. Phase 3 study to determine the efficacy and safety of lenalidomide combined with melphalan and prednisone in patients ≥ 65 years with newly diagnosed myeloma (abstract).
In the past, interferon produced a moderate increase in PFS,[21] but because of toxicity, long-term treatment could not be justified.

29. Treatment options for multiple myeloma have grown a great deal in the past few years. One-year update of a phase 3 randomized study of daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) versus bortezomib, melphalan, and prednisone (VMP) in patients (pts) with transplant-ineligible newly diagnosed multiple myeloma (NDMM): ALCYONE. Thalidomide for relapsed or refractory myeloma. Mateos MV, Oriol A, Martinez J, et al. Bortezomib, melphalan, prednisone and thalidomide (VMPT) followed by maintenance with bortezomib and thalidomide for initial treatment of elderly multiple myeloma patients [abstract]. MP was a mainstay of therapy for a long time despite low CR rates. Abbreviation: ISS, international staging system. vs40.1 months, and 49 Abbreviations: ADL, activities of daily living; ALT, alanine aminotransferase; ASCT, autologous stem cell transplantation; AST, aspartate aminotransferase; CCI, Charlson comorbidity index; Dara, daratumumab; DLCO, diffusion capacity of carbon monoxide; FEV1, forced expiratory volume in 1 second; IADL, instrumental ADLs; IMWG, International Myeloma Working Group; LVEF, left ventricular ejection fraction; MEL, melphalan (with dosages in mg/m2); MM, multiple myeloma; Rd, lenalidomide and dexamethasone; Rd-R, lenalidomide and dexamethasone followed by lenalidomide maintenance; rMCI, revised myeloma comorbidity index; ULN, upper limit of normal; VCd, bortezomib, cyclophosphamide, dexamethasone; VMP, bortezomib, melphalan, and prednisone; VRd/vrd, bortezomib, lenalidomide, and dexamethasone. Conquer Cancer Foundation Elderly patients with multiple myeloma: towards a frailty approach?

[44] However, using the same regimen, the IFM failed to confirm this finding. San Diego, CA; 2018. 1 The median age of patients with myeloma is 70 years.

[17] PFS in the MPR-R arm was dramatically superior to PFS in the other two arms. PFS was not significantly different in those age 80 or older (median PFS, 10 months vs. 15 and 14 months in ages 75–79 and age 75 or younger, respectively). 2009;114:3139-46. vs28.1 months for patients achieving VGPR, with Rd continuous therapy JCO Clinical Cancer Informatics

In solid tumor oncology, there are well-validated measures to estimate the risk of toxicity of systemic therapy in older adults, and predictors include falls, hearing impairment, IADL dependence, nutritional compromise, and cognitive impairment.106-108 This approach will be tested in the MRC XIV Fitness Trial, wherein 740 patients will be randomly assigned to standard treatment with lenalidomide, ixazomib, and dexamethasone or to treatment dosing adapted to their level of frailty (NCT03720041). • PFS was significantly improved in the MPT arm in four out of five studies. Thus, the complexity of caring for older MM adults arises in part from the heterogeneity of aging, with factors influencing outcomes that include environmental factors (access to care and social support) and patient factors (comorbidities, functional status, and goals of care). ASCO Career Center M.C. contact us. An intermediate stage is smoldering (or asymptomatic) myeloma (SMM). An update of the study24  showed that outcome differences were sustained. We commonly see patients who have “exhausted all treatment options” and have bone marrow failure secondary to disease burden and extensive therapy. All rights reserved. Table 2 shows various induction regimens, several containing novel agents originally developed to treat relapsed/refractory disease.8-10  After the induction phase, thalidomide, bortezomib, and lenalidomide may be used, singly or in combination, as consolidation/maintenance therapy. 10. The risk of thrombosis is limited when these drugs are used alone, an option worth exploring in selected cases. COMy Online 2020 - Session 7 (Oral Abstracts). The dose of lenalidomide must be modified with renal dysfunction. Bortezomib and thalidomide have remarkable synergistic activity when used for induction with corticosteroids,17,36  albeit at the cost of increased toxicity compared with VMP.17  These drugs, administered as consolidation/maintenance therapy, increase CR rates17,25,36  and improve PFS.17  We often use bortezomib as maintenance therapy (J.M., S.S.: 1.3 mg/m2 once a month; M.C. Multiple myeloma affects adults of all ages, but it is primarily a disease of older persons. Kyle RA, Therneau TM, Rajkumar SV, et al. Harousseau JL, Palumbo A, Richardson PG, et al. Therapy for MM continues to evolve and includes novel combination therapy, new generations of targeted agents, immunotherapy, and increasing use of autologous stem cell transplantation (ASCT). Scarce data exist about octogenarians with MM, but investigations demonstrate similar PFS but inferior OS compared with younger patients. Research Funding: Janssen Oncology (Inst), Honoraria: Amgen Bristol-Myers Squibb Celgene Janssen-Cilag, Consulting or Advisory Role: Celgene Janssen-Cilag Takeda, Travel, Accommodations, Expenses: Amgen Celgene Janssen-Cilag, Research Funding: Abbvie (Inst) Acetylon (Inst) Janssen (Inst) Merck (Inst) Takeda (Inst). Older persons are susceptible to varicella-zoster virus reactivation because of age-related decline in varicella-zoster virus–specific cell-mediated immunity and treatment-induced immunosuppression. However, although in MGUS the risk of progression is uniform (about 1% per year), in SMM the risk is 10% per year for the first 5 years, approximately 3% per year for the next 5 years, and only 1% per year for the last 10 years. It is worthwhile switching to the once-weekly schedule if the standard schedule is not tolerated well.

Patients with myeloma frequently have symptoms and treatment toxicity that compromise health-related quality of life (HRQL). Larocca A, Salvini M, De Paoli L, et al. Multiple myeloma (MM) is a disease of older adults, and approximately 30,000 new occurrences will be diagnosed this year. However, several patient- and disease-related characteristics may suggest one approach over another in specific settings. ), or continuously (20-60 mg on a daily, alternate day or 3 times a week; J.M., S.S.). This usually composes 2 or 3 drugs: a novel agent (thalidomide, lenalidomide, or bortezomib) with corticosteroids with or without a cytotoxic agent, or 2 novel agents with corticosteroids. Population division: world population prospects 2017. https://population.un.org/wpp/.

Blood. [9] This discrepancy between the results of the Italian and French studies might be explained by the inclusion criteria, since patients aged 70 to 75 years were included in the French study but not in the Italian one. Although much is made of the “corticosteroid-free” nature of the PLD-bortezomib combination, the practical benefits of eliminating corticosteroids are limited.

Dispenzieri A, Kyle RA, Katzmann JA, et al. Rechallenge with any of the drugs is reasonable, provided it was effective when used previously and relapse did not occur too quickly. Abstract LBA-2. We avoid AHSCT in elderly patients with significantly compromised renal function unless it is clearly related to active myeloma that is unresponsive to other therapy. vsRd 18 months Results of the MM Hub poll onthe use of continuous therapy in elderly patients with MM. TABLE 3. Improved survival in multile myeloma and the impact of novel therapies. Interestingly, the Ld combination (lenalidomide and weekly dexamethasone) is commonly used even in patients who are ineligible for HSCT because of its excellent tolerance.19. Multiple myeloma is almost exclusively diagnosed in people aged 65 or older. 2006;108: 2365-72. Blood. In conclusion, PIs alone or with corticosteroids would be indicated for frail patients. Bortezomib plus melphalan and prednisone compared with melphalan and prednisone in previously untreated multiple myeloma: updated follow-up and impact of subsequent therapy in the phase III VISTA trial. 2007;110:2586-492. Br J Haematol.  |  [26] Prognostic factors that are associated with a shorter time to progression are listed in Table 6. The observation of decreased neuropathy with weekly dosing has now been confirmed.17,24,25  In one of the studies,17  bortezomib-melphalan-prednisone (VMP) induction followed by maintenance with bortezomib-thalidomide (VT) or bortezomib-prednisone (VP) was compared with bortezomib-thalidomide-prednisone (VTP) induction followed by VT or VP as maintenance. Brain natriuretic peptide should be monitored in patients with compromised heart function, especially while on therapy that can cause fluid retention.


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