Determining treatment intensity in elderly patients with multiple myeloma

Salvini, Marco; D’Agostino, Mattia; Bonello, Francesca; Boccadoro, Mario; Bringhen, Sara

doi:10.1080/14737140.2018.1496823

Cited by 10 publications

(10 citation statements)

References 66 publications

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“…In fit patients, treatment is aimed at achieving deep and durable responses (complete response or minimal residual disease negativity) and includes full-dose triplets/quadruplets and even ASCT in eligible patients. On the contrary, the prevention of toxicity and the preservation of quality of life are essential for intermediate-fit and frail patients [21,49]. Outcomes of main phase III trials in elderly MM patients at diagnosis are summarized in Table 1.…”

Section: Treatment Considerations For Intermediate-fit and Frail Patimentioning

confidence: 99%

Diagnostic and Therapeutic Challenges in the Management of Intermediate and Frail Elderly Multiple Myeloma Patients

Bonello

Boccadoro

Larocca

2020

Cancers

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Multiple myeloma (MM) mostly affects elderly patients, which represent a highly heterogeneous population. Indeed, comorbidities, frailty status and functional reserve may vary considerably among patients with similar chronological age. For this reason, the choice of treatment goals and intensity is particularly challenging in elderly patients, and it requires a multidimensional evaluation of the patients and the disease. In recent years, different tools to detect patient frailty have been developed, and the International Myeloma Working Group frailty score currently represents the gold standard. It identifies intermediate-fit and frail patients requiring gentler treatment approaches compared to fit patients, aiming to preserve quality of life and prevent toxicities. This subset of patients is underrepresented in clinical trials, and studies exploring frailty-adapted approaches are scarce, making the choice of therapy extremely challenging. Treatment options for intermediate-fit and frail patients might include dose-adapted combinations, doublets, and less toxic combinations based on novel agents. This review analyzes the available tools for the assessment of frailty and possible strategies to improve the discriminative power of the scores and expand their use in real-life and clinical trial settings. Moreover, it addresses the main therapeutic challenges in the management of intermediate-fit and frail MM patients at diagnosis and at relapse.

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Section: Treatment Considerations For Intermediate-fit and Frail Patimentioning

confidence: 99%

Diagnostic and Therapeutic Challenges in the Management of Intermediate and Frail Elderly Multiple Myeloma Patients

Bonello

Boccadoro

Larocca

2020

Cancers

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“…8,[10][11][12][13] It aims to individualize treatment decisions. [13][14][15] However, because of time-and personnelintensive demands, FA is not widely used in clinical routines in oncology. 1,2,8,15,16 Therefore, it seems important to identify the key scores and tests that are most important for patients with MM and have a relevant influence on their prognosis.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the prognostic significance of 5 comorbidity scores and 12 functional tests in a prospective multiple myeloma patient cohort

Scheubeck

Ihorst

Schoeller

et al. 2021

Cancer

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Background: Because of the various therapeutic options available for multiple myeloma (MM), remarkable interest exists today in individualized therapeutic concepts based on patients' fitness. The main objectives of this study were to compare different comorbidity scores and functional tests with respect to their impact on survival (overall survival [OS] and progression-free survival [PFS]); develop a timeefficient, MM-specific functional assessment (FA); and evaluate changes in patients' FA during treatment. Methods: The authors performed a prospective FA in 266 consecutive patients with MM at their initial diagnosis. This included 5 comorbidity scores and 12 commonly used geriatric functional tests. To evaluate changes in the course of treatment, the authors reassessed these 17 tests after ≥6 months. The entire analysis included 7327 FA tests. Results: On the basis of univariate and multivariate Cox regression analyses, the authors identified 4 of the 17 evaluated scores and functional tests as most relevant: the Revised Myeloma Comorbidity Index (R-MCI), Activity of Daily Living (ADL), the Mini-Mental State Examination (MMSE), and the quality-of-life 12-Item Short Form Health Survey Physical Composite Scale (SF-12 PCS). These showed precise group differences for fit, (intermediate-fit), and frail patients in OS and PFS: the 3-year OS rates were 90%, 74%, and 43% via the R-MCI for fit, intermediate-fit, and frail patients, respectively (P = .0006); 80% and 66% via the ADL for fit and frail patients, respectively (P = .0159); 78% and 48% via the MMSE for fit and frail patients, respectively (P = .0001); and 86% and 66% via the SF-12 PCS for fit and frail patients, respectively (P = .0091). In follow-up analyses, 16 of 17 FA tests improved, mostly in younger patients (<70 years old) and responding patients (partial remission or better). Conclusions: Patients may recover from functional and physical limitations under applied MM therapy. The newly established MM-specific FA (via the R-MCI, ADL, MMSE, and SF-12 PCS) allows a precise evaluation of the prognosis and risk status in MM. Its use may improve treatment tolerability and should be validated to individualize MM treatment decisions in the future. Cancer 2021;0:1-15.

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“…The average age was significantly lower for the 592 healthy controls than for the MM patients (P<0.001). This finding may be because MM is typical in elderly people, and over one-half of MM patients are older than 65 years at diagnosis 23, 24; in contrast, healthy controls were mainly recruited during their physical examinations, and these were mostly young men.…”

Section: Resultsmentioning

confidence: 99%

LRP1B Polymorphisms Are Associated with Multiple Myeloma Risk in a Chinese Han Population

Liu

Cheng

et al. 2019

J. Cancer

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Multiple myeloma (MM) is an extremely complex plasma cell malignancy that is genetically heterogeneous. A recent Genome-wide association study (GWAS) indicated that variation at 2q22 (rs61070260) influences MM risk. This association has not been validated to date in a Chinese Han population. In this study, we evaluated the association between rs61070260 in LRP1B and MM risk in a Chinese Han population involving 739 MM patients and 592 healthy controls. Our results indicated that rs61070260 in LRP1B was significantly associated with MM susceptibility (P=3.937×10-37). Furthermore, the linkage disequilibrium (LD) analysis of rs61070260 revealed an LD block encompassing exons 26, 27 and 28 of the LRP1B gene, and a subsequent sequencing analysis identified three SNPs (rs762074421, rs756168629, rs113600691) in exons 26 and 28 of LRP1B. For the SNP rs756168629 in exon 26, a missense mutation which results in a transition from arginine to histidine at position 1661 of the LRP1B protein, has not been found in Chinese populations according to the Chinese Millionome Database and Genome Aggregation Database (EAS), and this mutation was predicted to be deleterious or damaging by SIFT and PolyPhen. These findings firmly establish the role of LRP1B in contributing to MM susceptibility. In addition, the identification of a rare coding mutation (p.R1661H) in LRP1B detected in MM individuals was suggested to be harmful to the encoded protein, which was characterized as a candidate tumour suppressor; thus, LRP1B is likely to be a disease-associated gene that is implicated in the development and progression of MM.

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Determining treatment intensity in elderly patients with multiple myeloma

Cited by 10 publications

References 66 publications

Diagnostic and Therapeutic Challenges in the Management of Intermediate and Frail Elderly Multiple Myeloma Patients

Diagnostic and Therapeutic Challenges in the Management of Intermediate and Frail Elderly Multiple Myeloma Patients

Comparison of the prognostic significance of 5 comorbidity scores and 12 functional tests in a prospective multiple myeloma patient cohort

LRP1B Polymorphisms Are Associated with Multiple Myeloma Risk in a Chinese Han Population

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