Rapidly changing myeloma epidemiology in the general population: Increased incidence, older patients, and longer survival

Turesson, Ingemar; Björkholm, Magnus; Blimark, Cecilie; Kristinsson, Sigurður Y.; Vélez, Ramón; Landgren, Ola

doi:10.1111/ejh.13083

Cited by 130 publications

(107 citation statements)

References 48 publications

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“…Multiple myeloma (MM) is a neoplasm of clonal plasma cells accounting for 1.8% of all cancers. MM is the second most common hematologic malignancy, with an estimated 30,280 new myeloma cases and 12,590 deaths in the U.S. in 2017 . In recent years, with novel therapies and a better understanding of the biology of MM, more patients achieve lasting remission, and there is an increased overall survival rate .…”

Section: Introductionmentioning

confidence: 99%

Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

et al. 2019

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Section: Introductionmentioning

confidence: 99%

Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

et al. 2019

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“…The 5-year survival rate of MM is approximately 50% 7 , which is nearly double what it was in the late 1980s. 8 The reason for the improved outcomes is a series of therapeutic advances that include the introduction of autologous stem cell transplants (ASCT), immunomodulatory drugs (IMiDs), and proteasome inhibitors (PIs), all of which are now first-line therapies.…”

Section: Introductionmentioning

confidence: 93%

“…8 The reason for the improved outcomes is a series of therapeutic advances that include the introduction of autologous stem cell transplants (ASCT), immunomodulatory drugs (IMiDs), and proteasome inhibitors (PIs), all of which are now first-line therapies. 7–9 Despite the success of these treatments in extending the overall survival (OS) by 6-10 years, depending upon age at diagnosis, most patients eventually relapse and become refractory to the therapies that they had received. 10–12 The mechanisms by which patients develop resistance to these therapies are only partially understood and are thought to depend critically upon the BM microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Genetic program activity delineates risk, relapse, and therapy responsiveness in Multiple Myeloma

Wall

Turkarslan

et al. 2020

Preprint

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38Despite recent advancements in the treatment of multiple myeloma (MM), nearly all patients 39 ultimately relapse and many become refractory to their previous therapies. Although many 40 therapies exist with diverse mechanisms of action, it is not yet clear how the differences in MM 41 biology across patients impacts the likelihood of success for existing therapies and those in the 42 pipeline. Therefore, we not only need the ability to predict which patients are at high risk for 43 disease progression, but also a means to understand the mechanisms underlying their risk. We 44 hypothesized that knowledge of the biological networks that give rise to MM, specifically the 45 transcriptional regulatory network (TRN) and the mechanisms by which mutations impact gene 46 regulation, would enable improved predictions of disease progression and actionable insights for 47 treatment. Here we present a method to infer TRNs from multi-omics data and apply it to the 48 generation of a MM TRN that links chromosomal abnormalities and somatic mutations to 49 downstream effects on gene expression via perturbation of transcriptional regulators. We find that 50 141 genetic programs underlie the disease and that the activity profile of these programs fall into 51 one of 25 distinct transcriptional states. These transcriptional signatures prove to be more 52 predictive of outcomes than do mutations and reveal plausible mechanisms for relapse, including 53 the establishment of an immuno-suppressive microenvironment. Moreover, we observe subtype-54 specific vulnerabilities to interventions with existing drugs and motivate the development of new 55 targeted therapies that appear especially promising for relapsed refractory MM. 56 57 Introduction 58 59 Multiple Myeloma (MM) is a cancer of malignant plasma cells in the bone marrow (BM) that has 60 a prevalence of approximately 86,000 new cases per year. 1 Several clinical subtypes of MM have 61 been established on the basis of characteristic cytogenetic features, including various 62 translocations, gain or loss of chromosomal arms, deletion of specific chromosomes, and 63 hyperdiploidy. 2-4 Accordingly, MM is a complex disease of great heterogeneity that exhibits64 subtype-specific drivers of progression. 5,6 Efforts to better characterize the biology and 65 therapeutic vulnerabilities of MM have increased exponentially in recent years, as can be seen 66 from the number of research articles, clinical trials, and public availability of matched genomic, 67 transcriptomic, and patient data. However, the myriad combinations of chromosomal aberrations 68 and somatic mutations, coupled with the complex dependence of MM progression on the BM 69 microenvironment, have precluded a mechanistic understanding of the disease on a patient-70 specific level. 72The 5-year survival rate of MM is approximately 50% 7 , which is nearly double what it was in the 73 late 1980s. 8 The reason for the improved outcomes is a series of therapeutic advances that 74 include the introduction of autologous stem cell t...

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“…After year 2000, the introduction of more effective treatment agents in MM begun. [19][20][21] This includes the immunomodulators thalidomide and lenalidomide and the proteasome inhibitor bortezomib that were used increasingly during the latter calendar period, and were used in over 80% of all MM patients in Sweden in 2013. 31 Previous studies have shown that bortezomib can both inhibit growth of osteoclasts, and stimulate osteoblasts, thereby leading to bone healing in MM.…”

Section: Our Analyses On Different Subgroups Of Fractures In MM Patiementioning

confidence: 99%

“…Furthermore, to compare the effect of fractures on survival in MM before and after the introduction of novel treatment agents that have greatly improved survival in the MM patient population. [19][20][21]…”

Section: Introductionmentioning

confidence: 99%

Fractures and survival in multiple myeloma: results from a population-based study

et al. 2019

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Multiple myeloma causes lytic bone lesions and fractures. The impact of fractures on multiple myeloma survival is unclear. The aim of this study was to evaluate the effect of fractures on survival in multiple myeloma using data from multiple myeloma patients diagnosed in Sweden in the years 1990-2013, identified from the Swedish Cancer Registry. Information on date of birth, multiple myeloma diagnosis, fractures, and death was collected from central registries.A Cox regression model was used to compare survival in patients with and without a fracture at multiple myeloma diagnosis and another Cox model was used with fracture as a timedependent variable to assess the effect of fracture on survival after multiple myeloma diagnosis. Results were adjusted for age, sex, year of diagnosis, and previous fractures. A total of 14,013 patients were diagnosed with multiple myeloma during the study, thereof 1,213 (8.7%) were diagnosed with a fracture at multiple myeloma diagnosis, and 3,235 (23.1%) after diagnosis. Patients with a fracture at diagnosis were at a significantly increased risk of death (hazard ratio=1.28; 95% confidence interval: 1.19-1.37). The risk of death was significantly increased in patients with a fracture after multiple myeloma diagnosis (2.00; 1.90-2.10). The impact of fractures on survival did not change significantly between the two calendar periods 1990-1999 and 2000-2013 (0.98; 0.89-1.08). Our large study shows that multiple myeloma patients with fractures are at a significantly increased risk of dying compared to those without fractures which stresses the importance of preventing bone disease in multiple myeloma.

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Rapidly changing myeloma epidemiology in the general population: Increased incidence, older patients, and longer survival

Cited by 130 publications

References 48 publications

Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Patient-Reported Factors in Treatment Satisfaction in Patients with Relapsed/Refractory Multiple Myeloma (RRMM)

Genetic program activity delineates risk, relapse, and therapy responsiveness in Multiple Myeloma

Fractures and survival in multiple myeloma: results from a population-based study

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