del(17p) without TP53 mutation confers a poor prognosis in intensively treated newly diagnosed patients with multiple myeloma
TL;DR: This study clearly confirms the extremely poor outcome of patients displaying "double hit", but also confirms that del(17p) alone is still a very high-risk feature, confirming its value as a prognostic indicator for poor outcome.
About: This article is published in Blood.The article was published on 2021-03-04. It has received 37 citations till now. The article focuses on the topics: Population.
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TL;DR: How to optimally define risk and why a revision of the current definition is urgently needed are reviewed and discussed.
32 citations
TL;DR: The median overall survival in multiple myeloma patients is rapidly approaching 10 years; however, in nearly a fifth of patients the prognosis remains poor as discussed by the authors, therefore, the modern-day management of patients should be individualized, with more intense and continuous approach in these high-risk patients.
Abstract: The median overall survival in multiple myeloma is rapidly approaching 10 years; however, in nearly a fifth of patients the prognosis remains poor. Therefore, the modern-day management of myeloma patients should be individualized, with more intense and continuous approach in these high-risk patients. This includes first-line treatment based on multi-drug combinations employing the most effective drugs combinations, upfront autologous stem cell transplantation (in eligible patients with tandem transplantation being a consideration), and maintenance based on proteasome inhibitor-based combinations. This paper reviews the results of recent retrospective analyses and clinical trials, but also gives a glance into future by presenting the ongoing trials. This article is protected by copyright. All rights reserved.
14 citations
TL;DR: In this paper , the authors discuss the principles that can enable the rational and effective development of therapeutic approaches for high-risk multiple myeloma, and propose a more personalized approach to therapy.
Abstract: Summary: The multiple myeloma treatment landscape has changed dramatically. This change, paralleled by an increase in scientific knowledge, has resulted in significant improvement in survival. However, heterogeneity remains in clinical outcomes, with a proportion of patients not benefiting from current approaches and continuing to have a poor prognosis. A significant proportion of the variability in outcome can be predicted on the basis of clinical and biochemical parameters and tumor-acquired genetic variants, allowing for risk stratification and a more personalized approach to therapy. This article discusses the principles that can enable the rational and effective development of therapeutic approaches for high-risk multiple myeloma.
13 citations
TL;DR: In this paper , a review of risk stratification in NDMM is presented, which summarizes and compares the various established risk-stratification systems, go beyond the RISS and international myeloma working group risk stratifications to evaluate specific molecular and cytogenetic abnormalities and how they impact prognosis independently, and provide an outlook on developing a new high risk model system and how we might make sense of co-occurrences, oncogenic dependencies, and mutually exclusive mutations.
Abstract: Multiple myeloma (MM) is an acquired malignant plasma cell disorder that develops late in life. Although progression free and overall survival has improved across all age, race, and ethnic groups, a subset of patients have suboptimal outcomes and are labeled as having high risk disease. A uniform approach to risk in NDMM remains elusive despite several validated risk stratification systems in clinical use. While we attempt to capture risk at diagnosis, the reality is that many important prognostic characteristics remain ill-defined as some patients relapse early who were defined as low risk based on their genomic profile at diagnosis. It is critical to establish a definition of high risk disease in order to move towards risk-adapted treatment approaches. Defining risk at diagnosis is important to both effectively design future clinical trials and guide which clinical data is needed in routine practice. The goal of this review paper is to summarize and compare the various established risk stratification systems, go beyond the R-ISS and international myeloma working group risk stratifications to evaluate specific molecular and cytogenetic abnormalities and how they impact prognosis independently. In addition, we explore the wealth of new genomic information from recent whole genome/exome sequencing as well as gene expression data and review known clinical factors affecting outcome such as disease burden and early relapse as well as patient related factors such as race. Finally, we provide an outlook on developing a new high risk model system and how we might make sense of co-occurrences, oncogenic dependencies, and mutually exclusive mutations.
13 citations
TL;DR: In this article , the authors discuss the current definitions of HR and the need for a consensus, the results of available trials in HR patients, and the way through risk-adapted treatment strategies.
11 citations
References
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VU University Amsterdam1, Heidelberg University2, University of Barcelona3, Harvard University4, Complutense University of Madrid5, Lille University of Science and Technology6, Marche Polytechnic University7, Mayo Clinic8, Emory University9, Sapienza University of Rome10, University of Bologna11, University of Arkansas for Medical Sciences12, National and Kapodistrian University of Athens13, Cedars-Sinai Medical Center14, Erasmus University Rotterdam15, University of Navarra16, Centre Hospitalier Universitaire de Nantes17
TL;DR: The R-ISS is a simple and powerful prognostic staging system, and it is recommended for use in future clinical studies to stratify patients with NDMM effectively with respect to the relative risk to their survival.
Abstract: Purpose The clinical outcome of multiple myeloma (MM) is heterogeneous. A simple and reliable tool is needed to stratify patients with MM. We combined the International Staging System (ISS) with chromosomal abnormalities (CA) detected by interphase fluorescent in situ hybridization after CD138 plasma cell purification and serum lactate dehydrogenase (LDH) to evaluate their prognostic value in newly diagnosed MM (NDMM). Patients and Methods Clinical and laboratory data from 4,445 patients with NDMM enrolled onto 11 international trials were pooled together. The K-adaptive partitioning algorithm was used to define the most appropriate subgroups with homogeneous survival. Results ISS, CA, and LDH data were simultaneously available in 3,060 of 4,445 patients. We defined the following three groups: revised ISS (R-ISS) I (n = 871), including ISS stage I (serum β2-microglobulin level < 3.5 mg/L and serum albumin level ≥ 3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)], and normal LDH level (l...
1,350 citations
Emory University1, National and Kapodistrian University of Athens2, Princess Margaret Cancer Centre3, Medical University of Lublin4, Charles University in Prague5, University of Navarra6, Rabin Medical Center7, Ankara University8, Monash University9, Queen Mary University of London10, University of Texas MD Anderson Cancer Center11, Kyoto Prefectural University of Medicine12, Dresden University of Technology13, Bristol-Myers Squibb14, Harvard University15
TL;DR: Patients with relapsed or refractory multiple myeloma who received a combination of elotuzumab, lenalidomide, and dexamethasone had a significant relative reduction of 30% in the risk of disease progression or death.
Abstract: BackgroundElotuzumab, an immunostimulatory monoclonal antibody targeting signaling lymphocytic activation molecule F7 (SLAMF7), showed activity in combination with lenalidomide and dexamethasone in a phase 1b–2 study in patients with relapsed or refractory multiple myeloma. MethodsIn this phase 3 study, we randomly assigned patients to receive either elotuzumab plus lenalidomide and dexamethasone (elotuzumab group) or lenalidomide and dexamethasone alone (control group). Coprimary end points were progression-free survival and the overall response rate. Final results for the coprimary end points are reported on the basis of a planned interim analysis of progression-free survival. ResultsOverall, 321 patients were assigned to the elotuzumab group and 325 to the control group. After a median follow-up of 24.5 months, the rate of progression-free survival at 1 year in the elotuzumab group was 68%, as compared with 57% in the control group; at 2 years, the rates were 41% and 27%, respectively. Median progressi...
1,083 citations
TL;DR: In myeloma, the genomic aberrations t(4;14) and del(17p), together with beta2-microglobulin level, are important independent predictors of survival and have implications for the design of risk-adapted treatment strategies.
856 citations
Mayo Clinic1, University of Nantes2, Cedars-Sinai Medical Center3, Harvard University4, National and Kapodistrian University of Athens5, University of Barcelona6, Hackensack University Medical Center7, Icahn School of Medicine at Mount Sinai8, Lille University of Science and Technology9, Emory University10, University of Turin11, Wayne State University12, University of Hamburg13, United States Department of Veterans Affairs14, University of Salamanca15
TL;DR: It is proposed that future clinical trials in myeloma follow the guidelines for reporting results proposed in this manuscript, and detailed definitions for patient populations, lines of therapy, and specific endpoints are provided.
854 citations
National University of Singapore1, Mayo Clinic2, Queen Mary University of London3, Heidelberg University4, Columbia University5, Harvard University6, University of Turin7, Spanish National Research Council8, Erasmus University Medical Center9, University of Bologna10, University of Arkansas for Medical Sciences11, Cedars-Sinai Medical Center12
TL;DR: The International Myeloma Working Group proposes well-defined and easily applicable risk categories based on current available information and suggests the use of this set of prognostic factors as gold standards in all clinical trials and form the basis of subsequent development of more complex prognostic system or better prognostic Factors.
Abstract: Multiple myeloma is characterized by underlying clinical and biological heterogeneity, which translates to variable response to treatment and outcome. With the recent increase in treatment armamentarium and the projected further increase in approved therapeutic agents in the coming years, the issue of having some mechanism to dissect this heterogeneity and rationally apply treatment is coming to the fore. A number of robustly validated prognostic markers have been identified and the use of these markers in stratifying patients into different risk groups has been proposed. In this consensus statement, the International Myeloma Working Group propose well-defined and easily applicable risk categories based on current available information and suggests the use of this set of prognostic factors as gold standards in all clinical trials and form the basis of subsequent development of more complex prognostic system or better prognostic factors. At the same time, these risk categories serve as a framework to rationalize the use of therapies.
489 citations