scholarly journals Patient similarity network of newly diagnosed multiple myeloma identifies patient subgroups with distinct genetic features and clinical implications

2021 ◽  
Vol 7 (47) ◽  
Author(s):  
Sherry Bhalla ◽  
David T. Melnekoff ◽  
Adolfo Aleman ◽  
Violetta Leshchenko ◽  
Paula Restrepo ◽  
...  
2020 ◽  
Author(s):  
Sherry Bhalla ◽  
David Melnekoff ◽  
Jonathan Keats ◽  
Kenan Onel ◽  
Jeffrey Sawyer ◽  
...  

Abstract The remarkable genetic heterogeneity of Multiple Myeloma poses a significant challenge for proper prognostication and clinical management of patients. Here, we introduce MM-PSN, the first multi-omics Patient Similarity Network of Myeloma. MM-PSN enabled accurate dissection of the genetic and molecular landscape of the disease and determined twelve distinct sub-groups defined by five data types generated from genomic and transcriptomic patient profiling of 655 patients. MM-PSN revealed that 1q gain is the most important single lesion conferring high risk of relapse and that it can improve on the current International Staging Systems (ISS and R-ISS). Several sub-groups uncovered novel associations between the gain of 1q and other adverse secondary lesions, thereby identifying the chromosomal hallmarks of sub-clonal heterogeneity and tumor progression in MM. We also determined gene vulnerabilities and potential therapeutic options for each sub-group and validated our prognostic model in an independent dataset.


2021 ◽  
Author(s):  
Joshua Richter ◽  
Karthik Ramasamy ◽  
Leo Rasche ◽  
Joan Bladé ◽  
Sonja Zweegman ◽  
...  

Newer treatments for multiple myeloma (MM) have improved response rates and survival for many patients. However, MM remains challenging to treat due to the propensity for multiple relapses, cumulative and emergent toxicities from prior therapies and increasing genomic complexity that arises due to clonal evolution. In particular, patients with relapsed/refractory MM often require increased complexity of treatment, yet still experience poorer outcomes compared with patients who are newly diagnosed. Additionally, several patient subgroups, including those with extramedullary disease and patients who are frail and/or have multiple comorbidities, have an unfavorable prognosis and remain undertreated. This review (based on an Updates-in-Hematology session at the 25th European Hematology Association Annual Congress 2020) discusses the management of these difficult-to-treat patients with MM.


Blood ◽  
2013 ◽  
Vol 121 (6) ◽  
pp. 884-892 ◽  
Author(s):  
P. Leif Bergsagel ◽  
María-Victoria Mateos ◽  
Norma C. Gutierrez ◽  
S. Vincent Rajkumar ◽  
Jesús F. San Miguel

Abstract Multiple myeloma (MM) is a heterogeneous disease with certain genetic features [eg, t(4;14), del17p] associated with worse outcome. The introduction of thalidomide, lenalidomide, and bortezomib has dramatically improved the outlook for patients with MM, but their relative benefit (or harm) for different genetic patient subgroups remains unclear. Unfortunately, the small number of patients in each subgroup frequently limits the analysis of high-risk patients enrolled in clinical trials. Strategies that result in survival of high-risk genetic subgroups approximating that of patients lacking high-risk features are said to overcome the poor prognostic impact of these high-risk features. This outcome has been difficult to achieve, and studies in this regard have so far been limited by inadequate sample size. In contrast, strategies that compare the survival of high-risk genetic subgroups randomized to different treatment arms can identify approaches that improve survival. This type of analysis is clinically useful, even if the absolute gains do not improve outcomes to levels seen in patients without high-risk cytogenetics. Reviewing available data in high-risk MM from this perspective, it appears that bortezomib has frequently been associated with improved survival, whereas thalidomide maintenance has sometimes been associated with a shorter survival.


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