Does Increased Body Mass Index Predispose Myeloma Patients to Fractures or Shortened Survival?.

Abstract Background: Obese individuals are at increased risk of developing myeloma (Pan et al, Am J of Epidemiol, 2004, Feb) and at increased risk of death, compared to non-obese individuals (Calle et al, N Engl J Med, 2003 April). However, a higher BMI is protective against the development of osteoporosis and fracture in the general population (Siris et al, JAMA, 2001 Dec). Objectives: To assess the effect of obesity on fracture risk and mortality in patients diagnosed with multiple myeloma. Patients and Methods: Retrospective chart review of all patients identified by the Tumor Registry with the diagnosis of multiple myeloma, diagnosed from 1999–2003, at a single center (n= 60). Median age: 66 (range: 39–91). The study group is comprised of the following characteristics: female (58%), African-American (82%), white (15%) and other races (3%). All patients with bone disease were treated with bisphosphonates. Results: According to the World Health Organization criteria for BMI, 32% were grade 1 obese (25–29.9kg/m2), 18% were grade 2 obese (30–34.9kg/m2), 13% were grade 3 or 4 obese (>35kg/m).2 Fracture occurred in 23 patients (38%), either at diagnosis or during follow up. The mean BMI of patients with fracture was 30.7 ± 7.2 kg/m 2. The mean BMI of patients without fracture was 26.5 ± 4.2 kg/m 2.T-test comparison between the 2 groups shows a statistically significant correlation between increased BMI and fracture occurrence (T value = 2.577, p= 0.013). Rank-Spearman correlation was used to assess the significance of age, gender and diabetes as confounding factors; none of these factors were shown contribute to the difference observed. This correlation also shows statistically significant correlation between increased BMI and number of fractures (p= 0.035). Mean BMI of patients with rib fractures was 27.7kg/m2 (N=6), vertebral compression fractures was 31.8 (N=13), pathologic femur fractures was 30.3 (N=5) and all other types was 27.0 (N=4). The BMI is numerically greater in patients with fractures of weight bearing bones, but this difference did not reach statistical significance. Of the 60 patients studied, 27 patients have died. The median survival of patients with a normal BMI (<25 kg/m2) was 50 months, and that of patients with an increased BMI (≥25 kg/m2) was 58 months (p>0.05). Patients with poor performance status experienced shorter survival (p= 0.013). Conclusions: Although a higher BMI is protective against the development of osteoporosis in the general population, our study shows that higher BMI correlates with a greater incidence of osteoporosis and fracture in patients with multiple myeloma. Our results suggest that reduction of BMI should be recommended to reduce the likelihood of fracture and related complications. Prospective studies of larger populations to assess the impact of BMI and weight loss on fracture development are needed. BMI does not appear to impact on the length of survival of these patients. Limitations of this study include its retrospective nature, small sample size, ethnic distribution and location at a single institution.

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

Blood ◽

10.1182/blood.v120.21.760.760 ◽

2012 ◽

Vol 120 (21) ◽

pp. 760-760

Author(s):

Tanya Wildes ◽

Suhong Luo ◽

Graham A Colditz ◽

Kenneth R. Carson

Keyword(s):

Cardiovascular Disease ◽

Multiple Myeloma ◽

Renal Impairment ◽

Proportional Hazards ◽

First Year ◽

Risk Of Death ◽

Increased Risk ◽

Comorbidity Index ◽

The Impact ◽

Over Time

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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Impact of changes in heart rate with age on all-cause death and cardiovascular events in 50-year-old men from the general population

Open Heart ◽

10.1136/openhrt-2018-000856 ◽

2019 ◽

Vol 6 (1) ◽

pp. e000856 ◽

Cited By ~ 6

Author(s):

Xiao-jing Chen ◽

Salim Bary Barywani ◽

Per-Olof Hansson ◽

Erik Östgärd Thunström ◽

Annika Rosengren ◽

...

Keyword(s):

Heart Rate ◽

General Population ◽

Cardiovascular Events ◽

Population Sample ◽

Resting Heart Rate ◽

Risk Of Death ◽

Increased Risk ◽

Old Men ◽

The Impact ◽

Random Population Sample

BackgroundResting heart rate (RHR), a known cardiovascular risk factor, changes with age. However, little is known about the association between changes in RHR and the risk of cardiovascular events. The purpose of this study was therefore to assess the impact of RHR at baseline, and the change in RHR over time, on the risk of all-cause death and cardiovascular events.DesignA random population sample of men born in 1943 who were living in Gothenburg, Sweden was prospectively followed for a 21-year period.MethodsParticipants were examined three times: first in 1993 and then re-examined in 2003 and 2014. At each visit, a clinical examination, an ECG and laboratory analyses were performed. Change in RHR between 1993 and 2003 was defined as a decrease if RHR decreased by 5 beats per minute (bpm), an increase if RHR increased by 5 bpm or stable if the RHR change was <4bpm).ResultsParticipants with a baseline RHR of >75 bpm in 1993 had about a twofold higher risk of all-cause death (HR 2.3, CI 1.2 to 4.7, p=0.018), cardiovascular disease (CVD) (HR 1.8, CI 1.1 to 3.0, p=0.014) and coronary heart disease (CHD) (HR 2.2, CI 1.1 to 4.5, p=0.025) compared with those with <55 bpm in 1993. Participants with a stable RHR between 1993 and 2003 had a 44% decreased risk of CVD (HR 0.56, CI 0.35 to 0.87, p=0.011) compared with participants with an increasing RHR. Furthermore, every beat increase in heart rate from 1993 was associated with a 3% higher risk for all-cause death, 1% higher risk for CVD and 2% higher risk for CHD.ConclusionHigh RHR was associated with an increased risk of death and cardiovascular events in men from the general population. Moreover, individuals with an increase in RHR between 50 and 60 years of age had worse outcome.

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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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Hematologic Characteristics of Surviving Versus Non-Surviving COVID-19 Patients in Critical Care Units: Inner-City Hospital Experience, Detroit, MI

Blood ◽

10.1182/blood-2020-135869 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 33-34

Author(s):

Nino Balanchivadze ◽

Raef Fadel ◽

Jawad Sheqwara ◽

Philip Kuriakose

Keyword(s):

Inner City ◽

Henry Ford Hospital ◽

City Hospital ◽

Icu Admission ◽

Risk Of Death ◽

Increased Risk ◽

Unit Increase ◽

Henry Ford ◽

The Mean ◽

The Impact

Background As the COVID-19 pandemic spread across the US, the city of Detroit rose as one of the earliest infection epicenters in the nation. Henry Ford Hospital serves a diverse multi ethnic population in the inner city and throughout metropolitan Detroit, and thus provided care to a significant percentage of COVID 19 patients in the state of Michigan. Retrospective reviews have described different hematologic abnormalities in patients with COVID-19. Various markers, such as lymphopenia, neutrophilia, elevated ferritin, and DDimer levels have been identified as predictors of poor outcomes, intensive care unit (ICU) admission, and mortality. The aim of this study was to evaluate the impact of hematologic characteristics on the risk of intubation and mortality in our unique patient population infected with COVID-19 who required ICU admission. Methods: This was a retrospective medical record review of adult patients with laboratory-confirmed COVID-19 requiring admission to adult ICU at Henry Ford Hospital in Detroit, MI, from March 1 to April 15, 2020. The main outcomes assessed were death and need for intubation and mechanical ventilation. Results: A total of 229 patients met the study inclusion criteria. Of the 76 surviving patients analyzed, 40 (53%) were men and 36 (47%) were women, including 59 (78%) Black and 11 (14%) White patients. The mean age at presentation was 61 (SD, 15) years. Hypertension was the most common comorbidity (n=65 patients), followed by diabetes (n=39). Most surviving patients (n=60; 79%) were admitted to general practice units (GPU) and then transferred to ICU, while 49 (64%) patients required intubation. Among the 153 patients who died, 95 (62%) were men and 58 (38%) were women, with 41 (27%) being White and 99 (65%) Black. The mean age at presentation was 69 years (SD, 14.3). Hypertension was the most common presenting co-morbidity (n=118), followed by diabetes (n=72). More non-surviving patients were admitted directly to the ICU (n=71; 46%) and/or required intubation (n=147; 96%). Hematologic laboratory findings of the studied patients are represented in Table 1. Multivariate analysis of variables predictive of death and intubation are summarized in Table 2. Logistic modeling revealed an 18% increase in the odds of death and a 17% increase in odds of intubation for each unit increase in WBC. Also, for each unit increase in ANC, there was a 17% increase in odds of death and 21% increase in odds of intubation. Conclusions: Among patients with COVID-19 who required admission to ICU, Black patients were over-represented. Coronary artery disease (CAD), older age, and a lower oxygen saturation (SpO2) on initial triage in the emergency department were associated with increased mortality. A higher absolute neutrophil count (ANC) and white blood cell count (WBC) was associated with higher risk of intubation and death. Male sex and direct ICU admission were predictors of increased risk of intubation - and these patients were more likely to die. Contrary to other reports, lymphopenia did not increase odds of intubation or death in ICU, and neither the serum ferritin nor DDimer levels on admission were discriminators for death; however, higher peak levels during the hospitalization were linked to increased mortality. Inner city Black populations with advanced age, multiple co-morbidities, and COVID-19 may be at increased risk for ICU admission, and thereby at an increased risk of death. However, not all hematologic characteristics are generalizable with regard to intubation and mortality in ICU. Disclosures No relevant conflicts of interest to declare.

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Prevalence and Predictors of Non-Adherence to 6-Mercaptopurine (6MP) in Children with Acute Lymphoblastic Leukemia (ALL) - a Children’s Oncology Group Study.

Blood ◽

10.1182/blood.v112.11.897.897 ◽

2008 ◽

Vol 112 (11) ◽

pp. 897-897

Author(s):

Smita Bhatia ◽

Doojduen Villaluna ◽

Wendy Landier ◽

Alexandra Schaible ◽

Lindsey Hageman ◽

...

Keyword(s):

High School ◽

Household Income ◽

Lymphoblastic Leukemia ◽

Systemic Exposure ◽

Small Sample ◽

Future Research ◽

Annual Household Income ◽

Increased Risk ◽

The Mean ◽

The Impact

Abstract Use of contemporary risk-based therapy in children with ALL has resulted in five-year survival rates exceeding 80%. Achievement of durable remissions requires a maintenance phase composed of oral administration of antimetabolites (6-mercaptopurine and methotrexate) for approximately two years. Previous studies have shown that low systemic exposure to oral 6MP adversely affects prognosis, thus emphasizing the critical need for therapeutic levels throughout maintenance. However, significant inter-patient variability in red cell thioguanine nucleotide (6TGN – a major metabolite of 6MP) concentrations exists, and could in part be related to failure to adhere to prescribed therapy. Non-adherence in pediatric ALL patients has been reported – however, small sample sizes and varying methods of assessment make it difficult to understand the magnitude of this problem. The purpose of our study was to describe adherence to oral 6MP in a large multi-ethnic cohort of children with ALL. Patients were eligible to participate if they were diagnosed with ALL at age less than 22 years, belonged to one of four ethnic/racial groups (Asian, African-American, Caucasian, or Hispanic), and had completed at least 24 weeks of maintenance therapy. We have restricted the current report to Caucasians, where we have completed our target accrual. To measure 6MP adherence, we used the Medication Event Management System (MEMS) and supplied each patient with a MEMS TrackCap. This electronic cap allowed the collection of real-time data by recording the date and time(s) when the 6MP bottle was opened over a 6-month period. The MEMS data was downloaded at the end of the 6-month study period. Patients/parents also completed a self-administered sociodemographic questionnaire. Longitudinal analysis was performed using the Generalized Estimating Equations. A total of 173 Caucasian patients provided 26,424 person-days of observation for 6MP adherence. The median age at diagnosis was 5 years (1 to 19), and at study participation was 6 years (range, 2 to 20); median time from diagnosis was 18.8 months, and from start of maintenance, 8.1 months; 67% were males. NCI criteria for high-risk disease were present in 42% of the patients. The median annual household income was between $50K and $75K; 79% of the mothers and 72% of the fathers had received education beyond high school. The median number of household members (including patient) was 4 (range, 2 to 10). Adherence was defined as the ratio of 6MP bottle openings to actual 6MP doses prescribed, calculated as a percentage (“percent adherence”). Prescribed doses for the entire 6-month period were reviewed for each patient, and instances when 6MP was withheld by the prescriber due to toxicity or illness were taken into account for purposes of calculating adherence. The mean percent adherence over the 6-month study period was 85% (range 11% to 100%). The mean monthly percent adherence declined significantly over the 6-month study period (p=0.002). Multivariate analysis identified certain subgroups that were at increased risk of lower percent adherence (Figure): age >8 years at study entry (p=0.01); households that included members other than the mother, father, and patient (<0.001); father’s education ≤ high school or ≥ college degree (p=0.05), and annual household income <$20k or ≥ $100K (p=.045). In this study, 19% of the study participants were <80% adherent at the end of the first study month; this increased to 30% by the end of the 6-month study period. Over 6% of patients were <50% adherent at the end of the first month, and this increased to 11% at month 6 – demonstrating that over 10% of the patients were taking less than 50% of their prescribed doses of 6MP. This study demonstrates that non-adherence to 6MP is prevalent in children undergoing treatment for ALL and increases with time on maintenance. It further delineates certain sociodemographic variables that define those at highest risk for non-adherence. Patients from this study will be followed long-term to understand the impact of non-adherence on outcome. Future research needs to focus on developing targeted, multidisciplinary interventions to reduce non-adherence to therapy. Figure Figure

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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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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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