scholarly journals Validation of the UK myeloma research alliance risk profile, a new clinical prediction model for outcome in patients with newly diagnosed multiple myeloma not eligible for autologous stem cell transplantation; a population‐based study from the Danish national multiple myeloma registry

Author(s):  
Louise Redder ◽  
Tobias W. Klausen ◽  
Annette Juul Vangsted ◽  
Henrik Gregersen ◽  
Niels F. Andersen ◽  
...  
2017 ◽  
Vol 58 (9) ◽  
pp. 2101-2109 ◽  
Author(s):  
Joost C. de Vries ◽  
Berdien Oortgiesen ◽  
Marc H. Hemmelder ◽  
Eric van Roon ◽  
Robby E. Kibbelaar ◽  
...  

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 30-31
Author(s):  
Hira S Mian ◽  
Gregory R Pond ◽  
Branavan Sivapathasundaram ◽  
Tanya M. Wildes ◽  
Jonathan Sussman ◽  
...  

Introduction Multiple myeloma (MM) is an incurable malignant plasma cell disease with a median age at diagnosis of 70 years, making it a disease of older patients. Although there has been much progress made in the therapeutics of MM, there is a paucity of data with regards to the symptoms experienced by these patients. Patient reported outcomes (PROS) represent an opportunity to both understand the magnitude as well as the temporal trend of this symptom burden. In 2007, routine prospective collection of patient-reported Edmonton Symptoms Assessment System (ESAS) scores during all outpatient cancer clinic visits was initiated in Ontario, Canada. The ESAS is a validated and reliable tool that assesses the severity of nine common symptoms: well-being, pain, tiredness, anxiety, depression, drowsiness, lack of appetite, nausea and shortness of breath. The study of longitudinal data from an administrative data base provides a unique opportunity to understand the symptom burden experienced by MM patients in the 'real-world' at a population level. Methods We conducted a retrospective population-based study using administrative data from the Institute of Clinical Evaluative Sciences (ICES), which maintains a central database of health records for all patients in the publicly funded health care system for the province of Ontario, Canada. All patients with newly diagnosed multiple identified using the ICD-O-3 code 9732 (Multiple Myeloma), who received treatment, but no transplant in the first year, between the years Jan 2007-Dec 2018, were identified. The main outcome of interest was an ESAS score of ≥4 which has been shown to represent clinically significant moderate to severe symptom burden, within the first 12 months following MM diagnosis. Logistic regression was used to assess the association between baseline factors identified a priori and moderate to severe symptoms for each domain. Results A total of 4611 transplant ineligible patients with newly diagnosed myeloma were identified between the years 2007-2018. Of these, 2876 (62.3%) with at least one ESAS score following diagnosis were included in this analysis. This represented 27,701 unique ESAS assessments recorded during the first year, which were used to form the cohort. Baseline characteristics for transplant ineligible patients with one or more ESAS are shown in Table I. Trajectory for moderate to severe symptoms in each month following diagnosis is shown in Figure 1. A high proportion of the cohort reported moderate to severe symptoms at diagnosis, with tiredness (64%) and impaired well-being (60%) being among the most prevalent and nausea being the least prevalent (13%). Most symptoms decreased over the first year, with the largest decline happening in the first 3 months. One year following diagnosis, there continued to be a substantial burden of symptoms, with over 25% of the cohort reporting at least one or more of the following moderate-severe symptoms: tiredness, pain, impaired well-being, drowsiness or loss of appetite. Self-reported depression rates marginally decreased over time; however, at the end of one year, 18% of cohort still reported moderate to severe depression. On multivariable analysis, younger age, female sex, urban geographic location, poor socioeconomic status, an earlier diagnosis year, myeloma defining end-organ damage and non-teaching hospital were associated with a higher odds of reporting moderate to severe symptoms. Conclusion Our results demonstrate that there is considerable symptom burden during the first year following MM diagnosis, with tiredness, impaired well-being and pain being the most common. Although symptoms improve over time, a significant proportion of patients continue to experience moderate to severe symptoms one-year post diagnosis. This study represents the largest population-based cohort study done to date in symptom burden among patients with MM. Future studies aimed at targeted intervention are needed early in the disease course in order to alleviate symptoms burden for at-risk patient groups. Disclosures Mian: Takeda: Consultancy, Honoraria; Celgene: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Sanofi: Consultancy. Pond:Roche Canada: Other; Astra Zeneca: Consultancy; Takeda: Honoraria. Wildes:Janssen: Research Funding; Seattle Genetics: Consultancy; Carevive Systems: Consultancy.


2021 ◽  
Vol 11 (11) ◽  
Author(s):  
Mirian Brink ◽  
Kaz Groen ◽  
Pieter Sonneveld ◽  
Monique C. Minnema ◽  
Annemiek Broijl ◽  
...  

AbstractIdentification of risk factors for early mortality (EM) in multiple myeloma (MM) patients may contribute to different therapeutic approaches in patients at risk for EM. This population-based study aimed to assess trends in EM and risk factors for EM among MM patients diagnosed in the Netherlands. All MM patients, newly diagnosed between 1989 and 2018, were identified in the Netherlands Cancer Registry. Patients were categorized into three calendar periods (1989–1998, 1999–2008, 2009–2018) and into five age groups (≤65, 66–70, 71–75, 76–80, >80 years). EM was defined as death by any cause ≤180 days post-diagnosis. We included 28,328 MM patients (median age 70 years; 55% males). EM decreased from 22% for patients diagnosed in 1989–1998 to 13% for patients diagnosed in 2009–2018 (P < 0.01) and this decrease was observed among all age groups. Exact causes of death could not be elucidated. Besides patient’s age, we found that features related to a more aggressive disease presentation, and patient characteristics reflecting patients’ physical condition were predictive of EM. In summary, EM decreased from 1999 onwards. Nevertheless, EM remains high, especially for patients aged >70 years. Therefore, novel strategies should be explored to improve the outcome of patients at risk for EM.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1849-1849
Author(s):  
Louise Redder ◽  
Tobias Wirenfeldt Klausen ◽  
Annette Juul Vangsted ◽  
Henrik Gregersen ◽  
Niels Frost Andersen ◽  
...  

Background : The UK Myeloma Research Alliance recently introduced a new clinical prediction model for outcome in newly diagnosed multiple myeloma (MM) patients not eligible for autologous hematopoietic stem-cell transplantation (ASCT) (Lancet Haematology 2019; 6: e154-66). The score or Myeloma Risk Profile, MRP, includes WHO performance status (PS), the International Staging System (ISS), age, and C-reactive protein (CRP) as prognostic variables. First a score is calculated by the formula: Score = (PS - 2) * 0.199 + (age - 74.4) * 0.0165 + (ISS - 2) * 0.212 + (log(CRP + 1) - 2.08) * 0.0315, where PS and ISS are defined as numbers between 0-4 and 1-3, respectively, and CRP is in mg/L. Next, three risk groups are defined as 1) low risk: score < -0.256, 2) medium risk: -0.256 ≤ score ≤ -0.0283, or 3) high risk: score > -0.0283. The MRP score was generated based on two prospective clinical trial cohorts, the NRCI-Myeloma XI study (ISRCTN49407852) as training set or internal validation, and the NRCI-Myeloma IX study (Blood 2011; 118, 1231-38) as test set or external validation. Both trials investigated conventional oral alkylating agents, cyclophosphamide or melphalan, in combination with thalidomide, lenalidomide, and/or bortezomib; thus including drugs typically used in treatment of elderly MM patients. Establishment of the model included 1852 patients in the training set, and 520 patients in the test set. All patients were recruited as part of clinical trials and therefore fulfilled defined inclusion and exclusion criteria. To validate the MRP score in a population-based setting we performed a study of the entire cohort of transplant ineligible MM patients in the Danish National MM Registry. Methods : The Danish MM registry started 01 January 2005. It includes registration of all diagnosed MM patients in Denmark and given first- and second-line treatment. A data validation study has been performed (J Clin Epidemiology, 2016; 8: 583-587). At 31 December 2014, 2,926 newly diagnosed treatment demanding MM patients were registered, hereof 1,803 patients were above 65 years and found ineligible for ASCT, and constituted the patient population for this study. Results: Of 1,803 transplant in-eligible but treatment demanding newly diagnosed MM patients above 65 years 426 patients had one or more missing values for calculation of the MRP score, most often this was caused by missing ISS. Thus, 1,377 patients were evaluable with a median follow-up of 40.9 months. Patients were treated according to standard of care in Denmark during the 10-years registration period which included upfront conventional alkylating agent, mostly melphalan in 37.7%, thalidomide-based in 25.6%, bortezomib-based in 26.1%, lenalidomide based in 2.7%, and only palliative, mostly steroid-based in 7.9%. The distribution of the risk groups according to MRP was as follows: low risk 28.5%, medium-risk 25.1%, and high-risk 46.4%. Ccompared to the UK datasets we had a higher proportion of high-risk patients which undoubtedly reflects that our cohort is population based. Median survivals for the 3 risk groups are presented in Table 1 and overall survival curves illustrated in Figure 1. The model performed well in separating the patients into subgroups with different survival risks. In conclusion, our real life population-based data confirm that the MRP score is a robust and valuable risk assessment tool for elderly newly diagnosed MM patients older than 65 and not eligible for ASCT. An important advantage of the MRP score is that it is calculated from simple parameters that should be part of everyday diagnostic work-up. Disclosures Vangsted: Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria; Jansen: Honoraria. Plesner:Takeda: Consultancy; Oncopeptides: Consultancy; Genmab: Consultancy; AbbVie: Consultancy; Celgene: Consultancy; Janssen: Consultancy, Research Funding. Frederiksen:Novartis: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Alexion: Research Funding; Abbvie: Research Funding. Abildgaard:Amgen: Research Funding; Takeda: Research Funding; Celgene: Research Funding; Janssen: Research Funding.


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