Comorbidities Impact Survival in Multiple Myeloma: Analysis of the Veterans Health Administration National Database

Abstract Abstract 760 Introduction: The incidence of multiple myeloma (MM) increases with age, and the prognosis worsens. Comorbidities increase in prevalence with age, yet little is known about the impact of comorbid medical conditions on outcomes in MM. Methods: In a retrospectively-assembled cohort study, all patients with MM diagnosed between 1998 and 2009 at a Veterans' Administration (VA) hospital were identified in the VA central cancer registry. Patients who received no treatment within 6 months of diagnosis were excluded, eliminating those with smoldering myeloma or who received supportive care only. Comorbidities were ascertained from ICD-9 codes present prior to the diagnosis of MM, and categorized using the Romano adaptation of the Charlson Comorbidity Index (CCI). The independent effects of age, race and comorbidities were examined using Cox proportional hazards modeling. The impact of individual comorbidities on survival was also examined, controlling for age and race. Results: A total of 2,968 patients were identified. The median age was 69 (range 27–92). The vast majority of patients (98%) were male; 28.6% of the patients were black. The median Charlson Comorbidity Index score was 2 (range 0–13). The frequencies of selected comorbidities were: diabetes (31%), renal impairment (23.8%), cardiovascular comorbidities (38.8%) and pulmonary (26.6%). The median overall survival (OS) for the entire cohort was 28.6 months at a median follow up of 26.8 months (range 0–137 months). On multivariate analysis, age was significantly associated with mortality [Hazard Ratio (HR) 1.03 per year (95% confidence intervals (CI) 1.03–1.04), p<0.0001]. Race was not significantly associated with survival [HR 0.99 (95% CI 0.90–1.09), p=0.81]. The median OS, adjusted for age and race, was 36.5 months for patients with no comorbidities, 33.9 months for patients with a CCI score of 1–2, 25.6 months for patients with a CCI score of 3–4 and 20.2 months for patients with a CCI score ≥5. The impact of comorbidities on survival violated the proportional hazards assumption, with a cut-point at 1 year, indicating that the influence of comorbidities varied over time. Relative to those with no comorbidities, the HR for death among those with a CCI score 1–2 was 1.20 (0.97–1.48) in the first year, and 1.03 (95% CI 0.89–1.18) subsequent to the first year; among those with a CCI score 3–4, the HR for death was 1.67 (95% CI 1.34–2.08) in the first year and 1.23 (95% CI 1.05–1.45) subsequently; among those with a CCI score ≥5, the risk of death in the first year doubled [HR 2.15 (95% CI 1.73–2.67)] and was increased 40% subsequently [HR 1.42 (95% CI 1.19–1.69)]. Individual prevalent comorbidities were then examined. Cardiovascular disease, renal impairment, and pulmonary disease were all significantly associated with mortality. In the first year after diagnosis, cardiovascular disease was associated with a 55% increase in mortality [HR 1.55 (95% CI 1.35–1.78)] while, subsequent to the first year, the risk was only increased about 20% [HR 1.19 (95% CI 1.07–1.39)]. The impact of renal impairment and pulmonary impairment did not vary over time; both were associated with a 25% increased risk of death [renal impairment HR 1.26 (95% CI 1.14–1.38); pulmonary disease HR 1.24 (95% CI 1.13–1.37)]. Diabetes was not associated with survival (HR 1.02, p=0.64) after controlling for age, race and cardiovascular, pulmonary or renal impairment. Conclusion: Age and comorbidities are independently associated with increased risk of mortality in MM. The influence of comorbidities varies over time, with the greatest impact noted in the first year after diagnosis of MM among those with a CCI score ≥3 and with cardiovascular disease. Further study is needed to determine whether this increased early mortality is related to increased risk of toxicity of therapy, inadequate MM therapy or both. Disclosures: No relevant conflicts of interest to declare.

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Significant Improvement of the Survival of Patients with Multiple Myeloma Presenting with Severe Renal Impairment After the Introduction of Novel Agents

Blood ◽

10.1182/blood.v120.21.948.948 ◽

2012 ◽

Vol 120 (21) ◽

pp. 948-948

Author(s):

Meletios A Dimopoulos ◽

Sosana Delimpasi ◽

Eirini Katodritou ◽

Eleftheria Hatzimichael ◽

Marie-Christine Kyrtsonis ◽

...

Keyword(s):

Multiple Myeloma ◽

Renal Impairment ◽

Conflicts Of Interest ◽

Early Death ◽

Novel Agents ◽

The Past ◽

Increased Risk ◽

Time Periods ◽

The Impact ◽

Over Time

Abstract Abstract 948 Renal impairment (RI) is a common presenting complication of multiple myeloma (MM) and is associated with increased risk of treatment related toxicity and early death. The management of RI in patients with MM requires vigorous supportive measures and the immediate institution of antimyeloma therapy. After the introduction of novel agents a significant improvement of the survival of patients with MM has been observed; however, the impact of these therapies on the survival of MM patients who present with RI has not been extensively studied. In order to analyze the impact of RI in newly diagnosed patients with MM over the past 20 years, we analyzed 1773 patients with symptomatic myeloma who were treated within the Greek Myeloma Study Group (GMSG). Patients were divided in groups according to the date of initial treatment (1/1/1990-31/12/1994, 1/1/1995-31/12/1999, 1/1/2000-31/12/2004, after 1/1/2005). Thalidomide became available in Greece after 1/1/2000 and bortezomib after 1/1/2005. eGFR was calculated by the modified MDRD formula and the degree of RI was rated as severe when eGFR was <30 ml/min, moderate when eGFR was 30–59 ml/min and mild (or no RI) when eGFR >60 ml/min. The frequency of RI over time was similar as well as the proportion of patients who presented with severe RI (17% vs. 21% vs. 17% vs. 19%) for the respective time periods (p=0.496). More patients >65 years started therapy after 2000 (44% vs. 50% vs. 59% vs. 59%, respectively, p<0.001), especially patients >75 years (13% vs. 18% vs. 24% vs. 32%, respectively, p<0.001). Anemia (Hb <10 g/dl; p=0.007) and ISS-3 disease (p=0.001) were more common after 1/1/1995; there were no other significant differences in the characteristics of the patients during the respective time periods. No patients received upfront novel agents before 31/12/1999, while 20% received upfront novel agent in the period 2000–2004 (almost exclusively thalidomide) and 73% after 1/1/2005 (mostly thalidomide and bortezomib). Myeloma response (≥PR) to frontline therapy was achieved in 56.5% & 54% of patients in the period 1990–1994 & 1995–1999 vs. 67% and 72% of patients in the periods 2000–2004 and after 2005 (p<0.001). The median survival of patients has improved significantly during the past 20 years: 39 months (1990-1994), 31 months (1995-1999), 40.5 months (2000-2004), 54 months after 2005 (p<0.001). The median OS for patients with severe RI has improved significantly from 18 months & 19.5 months in the 1990–1994 & 1995–1999 to 29 months and 32 months for the periods 2000–2004 and after 2005 (p=0.005). For patients with moderate RI the OS improved from 33 & 26 months between 1990–1994 & 1995–1999 to 40 & 44 months in the periods 2000–2004 and after 2005 (p=0.003). For patients with an eGFR ≥60 ml/min the OS improvement was less pronounced (48.5 months vs. 45 months vs. 51 months for the periods 1990–1994 & 1995–1999 & 2000–2004 respectively (p=0.076) and only after 2005 a significant improvement in OS is observed (median OS has not been reached; 3-year OS rate is 73%, p<0.001). For patients with severe RI early death rates (<2 months from initiation of therapy) were 12% vs. 7% for patients with moderate RI vs. 3% for patients with mild or no RI (p<0.001) and remained unchanged over time. We then adjusted for differences between groups in a multivariate model: treatment after 1/1/2000 was independently associated with improved survival compared to patients treated before 31/12/1999 (p<0.001). After adjusting for the degree of RI in the model, the hazards ratios (HR) for death for patients with severe RI for the 2000–2004 and after 2005 periods were 0.485 & 0.387 respectively compared to patients treated before 2000 (p<0.001 for both comparisons). For patients with moderate RI the respective HRs were 0.65 (p=0.003) & 0.57 (p=0.001), while for patients with mild or no RI the HRs were 0.85 (p=0.1) & 0.66 (p=0.003) for the 2000–2004 and after 2005 periods, respectively. In conclusion, the incidence of RI at diagnosis of MM has remained unchanged during the past 20 years, despite the increasing numbers of older patients who are diagnosed and treated for MM. The risk of early death is almost 2 to 4-fold higher in patients with severe RI vs. patients with moderate or no RI and has not improved over time. However, after the introduction of novel therapies there has been a significant improvement of the survival of patients with RI, which is more pronounced in patients with severe RI. Disclosures: No relevant conflicts of interest to declare.

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Comorbidities Influence Survival in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v118.21.3142.3142 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3142-3142 ◽

Cited By ~ 1

Author(s):

Tanya Wildes ◽

Ravi Vij ◽

Graham A Colditz

Keyword(s):

Multiple Myeloma ◽

Survival Data ◽

Cox Proportional Hazards ◽

Rank Test ◽

Age Group ◽

Entire Cohort ◽

Risk Of Death ◽

Increased Risk ◽

Comorbidity Index ◽

The Impact

Abstract Abstract 3142 Introduction: Advancing age is associated with poorer prognosis in patients with multiple myeloma (MM). Comorbidities increase in prevalence with age, but the impact of comorbidities on survival in patients with MM is not known. The purpose of this study was to examine the impact of comorbidities on survival in multiple myeloma. Methods: All patients (pts) with MM diagnosed and treated at Washington University School of Medicine in St. Louis, Missouri from 1999–2010 were identified from the Barnes-Jewish Hospital Oncology Data Services Database. The institution's cancer registrars retrospectively collect clinical, demographic and survival data in accordance with the American College of Surgeons Commission on Cancer guidelines. Comorbidities are graded as None, Mild, Moderate or Severe using the ACE-27 comorbidity index [Piccirillo et al. J Reg Mgmt 1999]. Patients without data on comorbidities were excluded from the study. The primary endpoint was overall survival (OS), calculated from the date of diagnosis and censored at the time of last follow-up. OS was estimated using the Kaplan-Meier method, and compared between comorbidity groups using the Log-Rank test. The independent effects of age and comorbidities were evaluated using Cox Proportional Hazards Modeling. Results: 569 patients were identified in the database. Median age of patients was 59 years (range 33–91 years); 54.8% were male, 45.2% were female; 74.9% were white, 23.2% were black, and 1.9% were other races/ethnicities. Based on the ACE-27 comorbidity index, 181 pts (31.8%) had no comorbid medical conditions, 226 (39.7%) had mild comorbidities, 115 (20.2%) had moderate comorbidities, 47 (8.3%) had severe comorbidities. In the entire cohort, the median OS was 49.2 months [95% confidence intervals (CI) 42.9 – 55.6 months]. Survival by comorbidity category and age group are shown in table 1. The differences in survival between comorbidity groups in each age group and the entire cohort were statistically significant (log-rank p<0.001). Severe comorbidities were associated with a significantly increased risk of death after controlling for age (HR 1.97, P=0.002). Conclusion: The presence and severity of comorbidities confer a poorer prognosis in patients with MM. Further study is needed to determine to what extent comorbidities directly impact survival versus impacting therapeutic decision-making and tolerance of therapy. Disclosures: Vij: Celgene: Honoraria, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Honoraria, Speakers Bureau.

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Difference in cardiovascular disease incidence by sociodemographic factors in adolescent and young adult (AYA) cancer survivors.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.6565 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. 6565-6565

Author(s):

Theresa Keegan ◽

Lawrence H. Kushi ◽

Qian Li ◽

Ann Brunson ◽

Marcio H. Malogolowkin ◽

...

Keyword(s):

Cardiovascular Disease ◽

Cancer Survivors ◽

Sociodemographic Factors ◽

Cancer Type ◽

Cvd Risk ◽

Risk Of Death ◽

Increased Risk ◽

Race Ethnicity ◽

The Impact

6565 Background: AYA cancer survivors are at increased risk of developing cardiovascular disease (CVD) compared to AYAs without a history of cancer. In AYA cancer survivors, few population-based studies have focused on CVD risk and none have considered whether the occurrence of CVD differs by sociodemographic factors. Methods: Analyses focused on 64,918 patients aged 15-39 y at diagnosis for one of 14 first primary cancers during 1996-2010 and surviving > 2 years after diagnosis, with follow-up through 2013. Data were obtained from the California Cancer Registry and State hospital discharge data. CVD included coronary artery disease, heart failure, and stroke. We estimated the cumulative incidence of developing CVD, accounting for death as a competing risk, stratified by race/ethnicity, neighborhood socioeconomic status (SES) at diagnosis, health insurance status at diagnosis/initial treatment and cancer type. We examined the impact of CVD on mortality using multivariable Cox proportional hazards regression with CVD as a time-dependent covariate. Results: Overall, 2374 (3.7%) patients developed CVD, and 7690 (11.9%) died over the follow-up period. Survivors of acute myeloid leukemia (12.6%), acute lymphoid leukemia (11.1%), central nervous system cancer (9.0%) and non-Hodgkin lymphoma (6.0%) had the highest incidence of CVD at 10-years. Incidence was significantly higher among Blacks (6.7%) at 10-years than non-Hispanic Whites (3.0%), Hispanics (3.7%) and Asian/Pacific Islanders (3.7%) (p < 0.001). AYA survivors with public or no insurance (vs private) had a higher 10-year incidence of CVD (5.8% vs 2.9%; p < 0.001), as did survivors residing in low (vs high) SES neighborhoods (4.1% vs 2.7%; p < 0.001). These sociodemographic differences in CVD incidence were apparent across most cancer sites. The risk of death was increased by five-fold or higher among AYAs who developed CVD. Conclusions: AYA cancer survivors who were uninsured or publicly insured, of Black race/ethnicity, or who resided in lower SES neighborhoods are at increased risk for developing CVD and experiencing higher mortality. The proactive management of CVD risk factors in these subgroups may improve patient outcomes.

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Abstract P353: Survival after Acute Coronary Syndrome in the Community

Circulation ◽

10.1161/circ.127.suppl_12.ap353 ◽

2013 ◽

Vol 127 (suppl_12) ◽

Author(s):

Sheila M McNallan ◽

Yariv Gerber ◽

Susan A Weston ◽

Jill Killian ◽

Shannon M Dunlay ◽

...

Keyword(s):

Acute Coronary Syndrome ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Survival Estimate ◽

Risk Of Death ◽

Coronary Syndrome ◽

Kaplan Meier ◽

Increased Risk ◽

Over Time

Background: Contemporary data on survival after incident acute coronary syndrome (ACS), including both myocardial infarction (MI) and unstable angina (UA), are limited. Objective: To describe survival after incident ACS, to determine if it differs by ACS type (MI or UA) and to determine whether it has improved over time. Methods: Olmsted County, MN residents hospitalized between 1/1/2005-12/31/2010 were screened for incident ACS. ACS was defined as either MI validated by standard epidemiological criteria or UA validated by the Braunwald classification. Patients were followed for death from any cause. Cox proportional hazards regression was used to determine whether survival differed by ACS type, while adjusting for year of diagnosis, age, sex and comorbidities. Results: Among 1,160 incident ACS cases (mean±SD age 66.9±14.8, 60% male), 35% were UA and 65% were MI. After a mean (SD) follow up of 3.7 (2.1) years, 274 deaths occurred. The 3-year Kaplan-Meier survival estimate for MI was 79.6% (95% CI: 76.7%-82.6%) and for UA was 84.9% (95% CI: 81.3%-88.6%) (log-rank p=0.011). The association of ACS type with survival differed by age (p=0.056). After adjustment for year of diagnosis, sex and comorbidities, no difference in survival was observed between ACS types among those aged <60 (HR for MI vs. UA: 0.64, 95% 0.29-1.42). By contrast, among patients aged 60-79, those with an MI had 2 times the risk of death compared to those with UA (HR: 2.04, 95% CI: 1.24-3.37). Patients aged 80 or older who had an MI had a 40% increased risk of death compared to patients of the same age who had UA (HR: 1.42, 95% CI: 1.02-1.98). There was no difference in survival over time (HR for 2010 vs. 2005: 0.91, 95% CI: 0.61-1.36). Conclusions: Survival did not differ between UA and MI patients younger than 60, however among patients 60 or older, survival was worse among those with an MI. Survival after ACS did not change over the study period.

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Clinical characteristics and treatment outcomes of newly diagnosed multiple myeloma with chromosome 1q abnormalities

Blood Advances ◽

10.1182/bloodadvances.2020002218 ◽

2020 ◽

Vol 4 (15) ◽

pp. 3509-3519 ◽

Cited By ~ 1

Author(s):

Nadine Abdallah ◽

Patricia Greipp ◽

Prashant Kapoor ◽

Morie A. Gertz ◽

Angela Dispenzieri ◽

...

Keyword(s):

Multiple Myeloma ◽

Clinical Characteristics ◽

Tumor Burden ◽

Disease Stage ◽

Cytogenetic Abnormalities ◽

Chromosome 1Q ◽

Risk Of Death ◽

High Tumor Burden ◽

Increased Risk ◽

The Impact

Abstract A gain in chromosome 1q (+1q) is among the most common cytogenetic abnormalities in multiple myeloma (MM). It is unclear whether +1q is independently associated with decreased overall survival (OS). The objective of this study was to evaluate the impact of +1q on clinical characteristics, treatment response, and survival outcomes. We included 1376 Mayo Clinic patients diagnosed with MM from 2005 to 2018 who underwent fluorescence in situ hybridization testing at diagnosis with a panel including the +1q probe. A gain in 1q was found in 391 patients (28%) and was associated with anemia, hypercalcemia, high tumor burden, International Staging System (ISS) stage 3, high-risk (HR) translocations, and chromosome 13 abnormalities. There was no difference in overall response or deeper responses to proteasome inhibitor (PI)–, immunomodulatory drug (iMiD)–, or PI plus IMiD–based induction. Time to next treatment was shorter in patients with +1q compared with those without +1q (19.9 vs 27.7 months; P < .001). On univariate analysis, +1q was associated with increased risk of death (risk ratio [RR], 1.9; P < .001), and decreased OS was seen in all treatment groups. +1q was independently associated with decreased OS on multivariate analysis when other HR cytogenetic abnormalities, ISS stage 3, and age ≥70 years were included (RR, 1.5; P < .001). Gain of >1 copy of 1q was not associated with worse OS compared with gain of 1 copy (4.9 vs 4.3 years; P = .21). +1q was associated with high tumor burden, advanced disease stage, and HR translocations. It is independently associated with decreased OS, even in the setting of novel therapy and transplant.

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The Impact of the NOD2/CARD15 Variant (3020insC) and PSMA6 Polymorphism (-8C>G) on the Development and Outcome of Multiple Myeloma

BioMed Research International ◽

10.1155/2020/7629456 ◽

2020 ◽

Vol 2020 ◽

pp. 1-15

Author(s):

S. Zmorzyński ◽

S. Popek-Marciniec ◽

W. Styk ◽

M. Wojcierowska-Litwin ◽

I. Korszeń-Pilecka ◽

...

Keyword(s):

Multiple Myeloma ◽

Progressive Disease ◽

Bone Marrow Cells ◽

Risk Of Death ◽

Automated Dna Sequencing ◽

Increased Risk ◽

Pcr Rflp ◽

Relationship Of ◽

The Impact

Introduction. Multiple myeloma (MM) is a hematological malignancy characterized by genetic variety. The 3020insC variant of the NOD2/CARD15 gene results in the upregulation of proinflammatory cytokines. Chronic inflammation and abnormal function of the proteasome system may lead to MM development. The polymorphism (-8C>G) in the PSMA6 gene affects proteasome activity. The aim of our study was to analyze the possible relationship of NOD/CARD15 and PSMA6 genes with the risk of development and outcome of MM, as well as the sensitivity to bortezomib (proteasome inhibitor) in cell cultures derived from MM patients. Objects and Methods. Genomic DNA from 100 newly diagnosed MM patients and 100 healthy blood donors was analyzed by methods such as PCR-RFLP (for PSMA6 genotyping) and automated DNA sequencing (for NOD2/CARD15 genotyping). In a subgroup of 50 MM patients, nucleated bone marrow cells were treated with bortezomib in vitro. Results. Patients with PSMA6 CG+GG genotypes had higher chances for progressive disease (OR=5.0, 95% CI 1.07-23.16, p=0.05), shorter overall survival taking into account the type of treatment (p=0.039), and increased risk of death due to MM at the level of tendency (OR=4.74, 95% CI 1.02-21.97, p=0.06). The presence of NOD2/CARD15 3020insC decreased the risk of renal dysfunction in MM (OR=0.23, 95% CI 0.07-0.74, p=0.009). The analyzed changes in NOD2/CARD15 and PSMA6 genes did not impact the MM risk. In an in vitro study, bortezomib increased the number of apoptotic cells at 8 nM and 12 nM between wild-type and 3030insC variants of NOD2/CARD15 (p=0.018 and p=0.03, respectively). Conclusion. The presented results suggest a possible impact of PSMA6 CG+GG genotypes on the MM outcome and the association of the NOD2/CARD15 variant with bortezomib in vitro sensitivity.

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The Impact of Fractures on Survival in Multiple Myeloma: Results from a Population-Based Study

Blood ◽

10.1182/blood-2018-99-115403 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 4490-4490

Author(s):

Sigrun Thorsteinsdottir ◽

Ingigerdur S Sverrisdottir ◽

Gauti Gislason ◽

Ola Landgren ◽

Ingemar Turesson ◽

...

Keyword(s):

Multiple Myeloma ◽

Board Of Directors ◽

Research Funding ◽

Cox Regression ◽

Population Based ◽

Advisory Committees ◽

Population Based Study ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Abstract Introduction Multiple myeloma (MM) causes lytic bone lesions, osteopenia, and fractures, which increase the morbidity of MM patients. Results from small previous studies have indicated that fractures in MM have a negative effect on survival. Aims The aim of the study was to evaluate the impact of fractures on survival in MM patients diagnosed in Sweden in the years 1990-2013. Furthermore, to analyze the effect of bone fractures at MM diagnosis on subsequent survival. Methods Patients diagnosed with MM in 1990-2013 were identified from the Swedish Cancer Registry. Information on date of birth, diagnosis, and death were collected from the Registry of Total Population. Information on all fractures were retrieved from the Swedish Patient Registry. Cox regression model was used with fractures as time-dependent variables. The effect of fractures on survival was assessed for any fracture or a subtype of fracture (a specific bone fracture or ICD-coded pathologic fracture). Either first fracture or the first subtype of fracture was used in the analysis. The effect of a fracture at MM diagnosis (within 30 days before or 30 days after MM diagnosis) on survival was also estimated using a Cox regression model. All models were adjusted for age, sex, time of diagnosis, and previous fractures. Results A total of 14,008 patients were diagnosed with MM in the study period. A total of 4,141 (29.6%) patients developed a fracture including fractures that occurred within a year before MM diagnosis and thereafter. Hereof 2,893 (20.7%) patients developed a fracture after MM diagnosis. The risk of death was significantly increased for patients that developed a fracture after the time of MM diagnosis with a hazard ratio (HR) of 2.00 (95% confidence interval (CI) 1.91-2.10) for all fractures combined. The risk of death was significantly increased for patients that developed all subtypes of fractures after MM diagnosis except ankle fractures. The risk of death was significantly increased for patients that developed pathologic fractures (HR=2.17; 95% CI 2.03-2.32), vertebral fractures (HR=1.73; 95% CI 1.61-1.87), hip fractures (HR=1.99; 95% CI 1.82-2.18), femoral fractures (HR=2.62; 95% CI 2.32-2.98), humerus fractures (HR=2.57; 95% CI 2.32-2.86), forearm fractures (HR=1.24; 95% CI 1.05-1.46), and rib fractures (HR=1.52; 95% CI 1.31-1.77), but not for ankle fractures (HR 1.07; 95% CI 0.79-1.44). A total of 942 (6.7%) of all MM patients were diagnosed with a fracture within 30 days before or 30 days after MM diagnosis. The patients with a fracture at diagnosis were at a significantly increased risk of death compared to those without (HR 1.31; 95% CI 1.21-1.41; Figure) Conclusions Our large population-based study, including over 14,000 patients diagnosed with MM in Sweden in the years 1990-2013, showed that MM patients that developed a fracture after the time of diagnosis were at twofold increased risk of dying compared to MM patients without a fracture. Furthermore, MM patients with a fracture at diagnosis had a 30% higher risk of dying compared to patients without a fracture. Our results indicate that fractures in MM reflect a more advanced disease at diagnosis and stress the importance of managing MM bone disease in all MM patients. Figure. Figure. Disclosures Landgren: Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy; Celgene: Consultancy, Research Funding; Amgen: Consultancy, Research Funding.

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Low Intracellular Water, Overhydration, and Mortality in Hemodialysis Patients

Journal of Clinical Medicine ◽

10.3390/jcm9113616 ◽

2020 ◽

Vol 9 (11) ◽

pp. 3616

Author(s):

Carolina Gracia-Iguacel ◽

Emilio González-Parra ◽

Ignacio Mahillo ◽

Alberto Ortiz

Keyword(s):

Proportional Hazards ◽

Hemodialysis Patients ◽

Cox Proportional Hazards ◽

Intracellular Water ◽

C Reactive Protein ◽

Reactive Protein ◽

Risk Of Death ◽

Cox Proportional Hazards Models ◽

Increased Risk ◽

Over Time

Background: In hemodialysis patients, extracellular water (ECW) overload predicts all-cause and cardiovascular mortality. The primary aim of the present study was to analyze changes in post-dialysis (i.e., following removal of excess ECW) ECW, intracellular water (ICW), and the overhydration (OH) parameter over time. Additionally, the association of these parameters with mortality was explored. Patients and methods: Prospective study of prevalent hemodialysis patients (n = 124) followed for a median of 20 (interquartile range (IQR) 8–31) months. In three visits, inflammation (C-reactive protein) and post-dialysis fluid status (bioimpedance, BIS) were assessed. Results: During follow-up, the overhydration (OH) parameter increased (−0.696 ± 1.6 vs. 0.268 ± 1.7 L; p = 0.007) at the expense of a decrease in intracellular water (ICW) (19.90 ± 4.5 vs. 18.72 ± 4.1 24 L; p = 0.006) with a non-significant numerical increase in ECW/ICW ratio (0.795 ± 0.129 vs. 0.850 ± 0.143; p = 0.055). Baseline ICW positively correlated with muscle mass and energy intake and negatively with C-reactive protein and it was lower in those who died than in survivors (15.09 ± 2.36 vs. 18.87 ± 4.52 L; p = 0.004). In Kaplan–Meier analysis, patients with low baseline ICW (≤17 L) and high ECW/ICW ratio (≥0.84) were at an increased risk of death. Baseline ICW was also associated with the risk of death in adjusted Cox proportional hazards models (HR 0.62 (0.40–0.98) p = 0.04). Conclusions: In hemodialysis patients, the post-dialysis OH parameter increased over time while ICW decreased, without changes in ECW. Low baseline post-dialysis ICW correlated with muscle wasting and inflammation and was an independent risk factor for mortality.

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Population Trends in Incidence of Second Malignant Neoplasm and Cause-Specific Mortality in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v130.suppl_1.682.682 ◽

2017 ◽

Vol 130 (Suppl_1) ◽

pp. 682-682

Author(s):

Luciano J. Costa ◽

Kelly N. Godby ◽

Saurabh Chhabra ◽

Robert Frank Cornell ◽

Parameswaran Hari ◽

...

Keyword(s):

Multiple Myeloma ◽

Hematopoietic Cell Transplantation ◽

Conflicts Of Interest ◽

Malignant Neoplasm ◽

Hematologic Malignancies ◽

Malignant Neoplasms ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Background: The management of patients with multiple myeloma (MM) has evolved significantly over the last two decades with increased utilization of autologous hematopoietic cell transplantation (AHCT) and introduction of proteasome inhibitors (PIs) and immunomodulatory agents (IMIDs) and concomitant improvement in survival, particularly in younger patients. Both AHCT and the IMID lenalidomide have been associated with increased risk of second malignant neoplasms (SMN) in clinical trials, with the risk reaching 6.9% at 5 years in a recent meta-analysis. We intended to assess whether an increase in incidence of SMN was evident at the population level and the impact of the changing SMN risk on survival of MM patients. Methods: We utilized the Surveillance, Epidemiology and End Results 13 (SEER 13) registries to analyze three cohorts of patients: those diagnosed during 1995-1999 (pre-thalidomide, limited use of AHCT, 15 years of follow up), 2000-2004 (post-thalidomide, pre lenalidomide and bortezomib, increased utilization of AHCT, 10 years of follow up) and 2005-2009 (post-lenalidomide and bortezomib, higher utilization of AHCT, 5 years of follow up). Follow up is current to the end of 2014. We included patients younger than 65 years at the time of diagnosis of MM as first malignant neoplasm to focus the analysis in patients more likely to receive AHCT and presumably prolonged lenalidomide exposure. For each cohort, we calculated the incidence of SMN considering death from any cause as a competing risk. Since comparison by era is subject to confounding by attained age, we analyzed and compared standardized incidence ratios (SIRs) for SMN and causes of death (COD) in intervals of 5 years: years 1-5 and years 6-10 from diagnosis. Results: There were 2,720 patients in the 1995-1999, 3,246 in the 2000-2004 and 3,867 in the 2005-2009 cohort. Median age of diagnosis was 56 years and 56.6% of the patients were males with no differences across cohorts. Non-Hispanic Whites were 55.9%, non-Hispanic Blacks 23.2%, Hispanics 12.6% and individuals of other race/ethnicities 8.2%. Median follow up of survivors was 198 months (range 1-239), 141 months (range 1-179) and 81 months (range 0-119) in the 1995-1999, 2000-2004 and 2005-2009 cohorts respectively. Cumulative incidences of SMN at 90 months were 4.7% (95% C.I. 4.0-5.6%), 6.0% (95% C.I. 5.2%-6.8%) and 6.3% (95% C.I. 5.5%-7.1%), respectively in the 3 consecutive cohorts, P=0.0008. The statistically significant, yet small increase in SMN is accompanied with decline in all-cause mortality in the same period from 69.9% for the 1995-1999 cohort to 60.4% for the 2000-2004 cohort to 52.8% for the 2005-2009 cohort, P<0.0001. During years 1-5 after MM diagnosis, the risk of another cancer of any type evolved from lower than expected in an age, gender and race-matched population for patients diagnosed in 1995-1999 (SIR=0.77, 95% C.I. 0.59-0.99) to similar to expected for patients diagnosed in 2005-2009 (SIR=1.15, 95% C.I. 0.97-1.36), driven particularly by increase in hematologic malignancies from SIR=1.28 (95% C.I. 0.47-2.78) to SIR=2.17 (95% C.I. 1.27-3.48),(Figure). For years 6-10, the overall risk of subsequent malignancy in MM survivors is similar to the matched population for both the 1995-1999 and the 2000-2004 cohorts (most recent cohort with 10-year follow up). However, the risk of subsequent hematologic malignancy is increased in both periods with the most substantial change being in the risk of lymphomas evolving from SIR=0.59 (95% C.I. 0.01-3.29) for the 1995-1999 cohort to SIR=3.31 (95% C.I. 1.51-6.27) for the 2000-2004 cohort. As expected, overall mortality in years 1-5 declined sharply across the three cohorts (Table), driven by decline in both MM-associated (from 159.4 to 91.7/1,000 patient-year) and cardiovascular mortality (from 12.6 to 9.1/1,000 patient-year). Importantly, there was no discernible increase in risk of death from SMN (from 4.5 to 3.9/1,000 patient-year). Conclusions: This population study confirms that the evolution of MM therapy in the US in the last 20 years is associated with a small, statistically significant increase in the risk of SMN in patients <65 years. Such increase is driven mostly by the increased incidence of hematologic malignancies. The study also demonstrates that the mortality from SMN is modest, has not significantly increased over time and is obscured by the robust reduction in mortality from MM. Disclosures No relevant conflicts of interest to declare.

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Venous Thromboembolism Is Associated with Increased Mortality in Patients with Multiple Myeloma

Blood ◽

10.1182/blood.v124.21.2176.2176 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2176-2176 ◽

Cited By ~ 1

Author(s):

Kristen M. Sanfilippo ◽

Suhong Luo ◽

Brian F Gage ◽

Katiuscia O'Brian ◽

Kenneth R. Carson

Keyword(s):

Multiple Myeloma ◽

Overall Survival ◽

Prognostic Factors ◽

Venous Thromboembolism ◽

Thrombotic Event ◽

Direct Result ◽

Health Administration ◽

Risk Of Death ◽

Increased Risk ◽

The Impact

Abstract Introduction: Previous studies have demonstrated conflicting results regarding the effect of venous thromboembolism (VTE) on survival in patients with multiple myeloma (MM). Recently, a population-based study demonstrated inferior overall survival in patients with MM and VTE (Kristinsson 2012). Given the nature of the data, the prior study was unable to verify venous thrombotic event or adjust for known confounding prognostic risk factors. In an attempt to verify the impact of VTE on survival in MM, we studied outcomes in a nationwide population of United States Veterans with MM. Methods: Patients with newly diagnosed MM treated within the Veterans Health Administration (VHA) system between September 1, 1999 and September 30, 2009 were identified within the VHA Central Cancer Registry. To avoid including patients with precursor states (i.e. monoclonal gammopathy of undetermined significance or smoldering myeloma), patients who did not receive treatment within 6 months of diagnosis were excluded. The cohort was followed using administrative data through April 22, 2013. Data on age, sex, race, body mass index (BMI), co-morbidities, treatment including transplant status, hemoglobin (HGB), albumin, and renal function were obtained. VTE was identified using an algorithm consisting of a combination of VTE international classification of diseases (ICD)-9 codes and VTE treatment data. Cox proportional hazards regression modeling was used to assess the association between VTE and overall survival while controlling for known prognostic factors. Results: The final analytic cohort consisted of 2785 patients of which 190 developed VTE after MM diagnosis (6.8%). After controlling for age, race, BMI, medical comorbidities, baseline lab characteristics, year of diagnosis, and upfront treatment with a novel agent (thalidomide, bortezomib, or lenalidomide), patients with MM and VTE had a 46% increased risk of death at 2 years compared to those without (table 1). This risk persisted at 5-year analysis; however, was no longer statistically significant (HR 1.16; 95% CI, 0.95-1.40). Conclusion: After controlling for known MM prognostic factors, VTE was significantly associated with increased mortality in the 2-years following MM diagnosis. Whether the observed increase in mortality is a direct result of VTE could not be determined in this study. Further study of MM patients with a high-risk for VTE, including studies of thromboprophylaxis, could clarify the significance of this association. Table 1:Increased Risk of Death from VTE in 2,785 US Veterans with MMHR for death within 2 years of MM diagnosis (95% CI)HR for death within 5 years of MM diagnosis (95% CI)VTE1.46 (1.13-1.89)1.15 (0.95-1.40)BMI < 18.5 25 <= BMI < 30 BMI >= 301.45 (1.09-1.93) 0.87 (0.76-0.99) 0.76 (0.65-0.89)1.50 (1.18-1.92) 0.87 (0.79-0.97) 0.78 (0.69-0.88)Age (year)1.01 (1.00-1.02)1.02 (1.01-1.02)Race (AA vs. non)0.87 (0.76-0.99)0.88 (0.79-0.97)HGB mg/dL1.30 (1.15-1.47)1.26 (1.14-1.39)HGB Unknown mg/dL (n=152)0.98 (0.73-1.30)0.88 (0.71-1.10)CrCl < 30 ml/min1.47 (1.28-1.68)1.42 (1.27-1.59)CrCl Unknown ml/min (n=184)1.15 (0.89-1.49)1.11 (0.90-1.10)Albumin <=3 g/dL1.42 (1.25-1.61)1.26 (1.14-1.40)Albumin Unknown g/dL (n=366)0.76 (0.62-0.94)0.85 (0.73-1.00)Year of Diagnosis0.99 (0.96-1.01)0.97 (0.95-0.99)Charlson Comorbidity Index1.08 (1.06-1.11)1.07 (1.05-1.10)Transplant0.22 (0.15-0.31)0.46 (0.38-0.55)Upfront Treatment with Novel Therapy0.47 (0.42-0.53)0.63 (0.57-0.70) Disclosures Carson: Spectrum: Consultancy; Celgene: Consultancy, Speakers Bureau.

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