Shah, Nilay D.

Abstract Background: Unlike acute lymphoblastic leukemia, data on acute myelogenous leukemia (AML) in the adolescents and young adults (AYA) are limited and generally derived from clinical trials, which are mostly conducted in academic centers. It is unclear whether the choice of treatment facility influences clinical outcome independent of disease biology and socio-demographic factors. This study used the National Cancer Data Base, a nationwide oncology database covering 70% of the US cancer population, to address this question. Methods: We identified 11,712 AYA patients who were diagnosed with AML from 2003-2011. We excluded patients who were: a) 15-17 years of age (n = 3,104) as treatment facility data were not available for age <18 years; b) not treated at the reporting facilities (n = 415) as follow-up might be incomplete; c) treated at treatment facilities with ≤100 new cancer cases/year (n = 18); and d) those without follow-up data (n = 47). Treatment facilities were classified as academic, comprehensive community (>500 new cancer cases/year), or community (101-500 new cancer cases/year) cancer programs. AMLs harboring t(15;17), inv(16), or t(8;21) were defined as good-risk, while the rest were considered non-good risk. Overall survival from the time of AML diagnosis was the primary outcome. We used multivariate imputation by chained equation to impute missing values, weighted Cox regression to obtain average hazard ratios (HRs), and pooled Wald c2 statistics to detect interaction. Results: We included 8,128 AYA patients with AML in the study and 25.2% were good risk. Among the good risk AMLs, 11.6%, 12.3%, and 76.1% had t(8;21), inv16, and t(15;17), respectively. The distribution of patients by treatment facility were academic (64.1%), comprehensive community (32.9%), and community (3.0%). After detecting an interaction between AML risk and type of treatment facility (P=0.038), we stratified treatment facility by AML risk and found significant differences in overall survival among good risk (P=0.02) but not non-good risk AML (P=0.19). This survival difference persisted even after adjusting for demographic (age, sex, race/ethnicity), socioeconomic (income, education, medical insurance), geographic (area of residence, travel distance), co-morbidities (Charlson-Deyo score), and treatment (receipt of chemotherapy) factors. Patients with good risk AML treated in comprehensive community cancer programs had a higher risk of death compared to those treated in academic programs (adjusted HR: 1.41, 95% CI: 1.11-1.79). For community cancer programs, the risk of death was also higher but did not reach statistical significance (adjusted HR: 1.22, 95% CI: 0.68-2.21). ). Subset analysis showed that the survival difference among those with good risk AML was observed in t(15;17) or acute promyelocytic leukemia (APL; P=0.02) but not in t(8;21) or inv16 (P=0.79). The disparity occurred primarily during the first month of APL diagnosis, wherein the risk of death was two-fold higher in community programs (Figure). Conclusions: Among AYA patients with AML, treatment at academic cancer programs was associated with a better survival, but only for the APL subgroup. Because APL comprises a fifth of all AMLs in the AYA and is a highly curable cancer, health care delivery research in APL should become a priority in this age group. Figure 1. Figure 1. Disclosures Al-Kali: Celgene: Research Funding.

Abstract Background: The optimal follow-up of MGUS patients, including frequency of visits and type of tests to order, is unknown because there are no evidence-based data available for guidance. Nevertheless, there are currently 4 clinical practice guidelines that are based on expert-consensus: UK-Nordic (2009), International Myeloma Working Group (IMWG; 2010), International Expert Consensus (IEC; 2010) and European Myeloma Network (EMN; 2014). Most guidelines recommend annual follow-up with laboratory tests until life expectancy becomes limited. How MGUS patients are followed in the US and whether clinical practice guidelines are being followed remain largely unknown. Methods: We conducted a retrospective analysis of adult (age >18 years) patients from 2006-2012 using theOptum Labs Data Warehouse,a large database including administrative claims information on >150 million privately insured and Medicare Advantage enrollees throughout the US. We identified patients with an incident diagnosis of MGUS (ICD9: 273.1) who had enrollment periods of>1 year pre- and>2 years post-diagnosis in order to exclude patients with a prior history or subsequent diagnosis of lymphoplasmacytic malignancy. We determined the overall outpatient follow-up practice patterns (visits or tests performed for MGUS), their variations over time and by geo-demographic subgroups, and concordance with current clinical practice guidelines Results: There were 10,349 MGUS patients who met the study criteria. The mean interval per MGUS follow-up visit was 13.1 months. The distribution of patients by mean interval between visits was: q<6 months (39.9%), q6-12 months (10.7%), q13-24 months (2.6%) and q>24 months (46.8%). There was a significant trend towards a higher proportion of patients being followed q<6 over time from 36.2% in 2006 to 43.7% in 2013 (P=0.01). Patients ≥70 years were more likely followed q<6 months, while those from the Northeast or ≤50 years were more likely followed q>24 months compared to their counterparts (P<0.01). Over half of patients≥80 years were being followed either q<6 (44.7%) or q6-12 (11.6%) months (Figure 1). Only about half of the patients diagnosed in 2013 were concordant with any of the available guidelines regardless of whether the guidelines were more aggressive (UK-Nordic/IEC) or more conservative (IMWG/EMN) in their follow-up recommendations (54.6% and 56.5%, respectively). The tests ordered during follow-up are shown in Figure 2. The most common tests were complete blood count, calcium, and creatinine as they were ordered in over half of the follow-up visits (56.5% to 68.4%). In 11.6% of the follow-up, a face-to-face visit was not associated with any ancillary test, while in 31.5%, the follow-up was comprised of ancillary tests only without a face-to-face visit. The test combination of complete blood count, calcium, creatinine, and serum protein electrophoresis with or without free light chain was ordered in 25.0% of the visits. Conclusions: In the US, the MGUS follow-up practice patterns varied demographically and geographically. Only half of the patients were followed according to current guideline recommendations. A large proportion of patients with limited life expectancy continued to undergo close follow-ups. Figure 1 Figure 1. Figure 2 Figure 2. Disclosures No relevant conflicts of interest to declare.

Abstract Background: Prior studies on the risk of progression of monoclonal gammopathy of undetermined significance (MGUS) into lymphoplasmacytic malignancies (LPMs) were almost exclusively in the White populations, comprised of limited number of patients residing in relatively small geographic areas, or included patients mostly detected by serologic screening as part of clinical study (as opposed to detected clinically during evaluation of symptoms suspicious for LPMs). Similar epidemiologic studies in a large, racially diverse population are lacking. Methods: We conducted a retrospective analysis of incident MGUS patients diagnosed from 2006-2013 using theOptum Labs Data Warehouse, a large database including administrative claims information on >110 million privately insured and Medicare Advantage enrollees throughout the United States. We identified patients with a diagnosis of MGUS (ICD9: 273.1) with 1-5 years of continuous enrollment. Each enrollment cohort based on the duration of follow-up (1-, 2-, 3-, 4-, or 5-year) was analyzed individually to help estimate the progression to cancer. We excluded patients who were diagnosed with LPMs within three months of MGUS diagnosis. We calculated the rate of progression into LPMs (chronic lymphocytic leukemia [CLL], light chain amyloidosis [AL], multiple myeloma [MM], non-Hodgkin lymphoma [NHL], and Waldenström macroglobulinemia [WM]) expressed as number per 100 person-years. Results: There were 14,728 MGUS patients for a total of 21,288 person-years of follow-up. The distributions of the number of patients and events according to the cohorts classified by duration of follow-up were: 1-year (14,728 patients; 243 events), 2-year (10,644 patients; 307 events), 3-year (7,333 patients; 299 events), 4-year (4,497 patients; 237 events), and 5-year (2,960 patients; 191 events). The rates of progression to LPMs were consistently highest during the first year after MGUS diagnosis (~2.00), generally declined by half during the second year and remained fairly stable thereafter (~1.00; Table 1). The rates of progression into LPMs overall as well as by demographics are shown in Table 2. The risk of progression was significantly higher among men (P < 0.01) and older patients (>50 years; P = 0.03) compared to their counterparts but similar among races (P = 0.15). Of the 243 patients who progressed, the distribution of LPMs was MM (70.0%), NHL (13.2%), WM (12.3%), AL (4.1%), and CLL (0.4%). Conclusions: Among patients withMGUS, the risk of transformation into LPMs is continuous although twice as high during the first year after MGUS diagnosis compared to subsequent years. The risk of transformation was higher among men and those who were older but did not differ among the racial subgroups. Our findings can be used to develop an optimal risk-based MGUS follow-up strategy that incorporates not only serum biomarkers but also demographic factors. Disclosures No relevant conflicts of interest to declare.

Background The American College of Cardiology and American Heart Association periodically revise clinical practice guidelines. We evaluated changes in the evidence underlying guidelines published over a 10‐year period. Methods and Results Thirty‐five American College of Cardiology/American Heart Association guidelines were divided into 2 time periods: 2008 to 2012 and 2013 to 2017. Guidelines were categorized into the following topic areas: arrhythmias, prevention, acute and stable ischemia, heart failure, valvular heart disease, and vascular medicine. Changes in recommendations were assessed for each topic area. American College of Cardiology/American Heart Association designated class of recommendation as level I, II , or III (I represented “strongly recommended”) and levels of evidence ( LOE ) as A, C, or C (A represented “highest quality”). The median number of recommendations per each topic area was 281 (198–536, interquartile range) in 2008 to 2012 versus 247 (190–451.3, interquartile range) in 2013 to 2017. The median proportion of class of recommendation I was 49.3% and 44.4% in the 2 time periods, 38.0% and 44.5% for class of recommendation II , and 12.5% and 11.2% for class of recommendation III . Median proportions for LOE A were 15.7% and 14.1%, 41.0% and 52.8% for LOE B, and 46.9% and 32.5% for LOE C. The decrease in the proportion of LOE C was highest in heart failure (24.8%), valvular heart disease (22.3%), and arrhythmia (19.2%). An increase in the proportion of LOE B was observed for these same areas: 31.8%, 23.8%, and 19.2%, respectively. Conclusions There has been a decrease in American College of Cardiology/American Heart Association guidelines recommendations, driven by removal of recommendations based on lower quality of evidence, although there was no corresponding increase in the highest quality of evidence.

Background: High-quality diabetes care is evidence-based, timely, and equitable. Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are the most recently approved class of glucose-lowering medications with additional cardio- and renal-protective benefits and low risk of hypoglycemia. Cardiovascular and kidney disease are among the most common chronic diabetes complications, whereas hypoglycemia is the most prevalent adverse effect of glucose-lowering therapy. We examine the sociodemographic and clinical factors associated with early SGLT2i initiation and appropriateness of use based on contemporaneous scientific evidence. Materials and Methods: Retrospective analysis of medical and pharmacy claims data from OptumLabs ® Data Warehouse for commercially insured and Medicare Advantage adult beneficiaries with diabetes types 1 and 2, who filled any glucose-lowering medication between January 1, 2013 and December 31, 2016. Demographic (age, sex, race, income), clinical (comorbidities), and insurance-related factors affecting first prescription for a SGLT2i were examined using multivariable logistic regression. Results: Among 1,054,727 adults with pharmacologically treated diabetes, 7.2% ( n = 75,500) initiated a SGLT2i. Patients with prior myocardial infarction (MI) (odds ratio [OR]: 0.94, 95% confidence interval [CI]: 0.91–0.96), heart failure (HF) (OR: 0.93, 95% CI: 0.91–0.94), kidney disease (OR: 0.80, 95% CI: 0.78–0.81), and severe hypoglycemia (OR: 0.96, 95% CI: 0.94–0.98) were all less likely to start a SGLT2i; P < 0.001 for all. SGLT2i were also less likely to be started by patients ≥75 years (OR: 0.57, 95% CI: 0.55–0.59, vs. 18–44 years), Black patients (OR: 0.93, 95% CI: 0.91–0.95, vs. White), and those with Medicare Advantage insurance (OR: 0.63, 95% CI: 0.62–0.64, vs. commercial). Conclusions: Younger, healthier, non-Black patients with commercial health insurance were most likely to start taking SGLT2i. Patients with MI, HF, kidney disease, and prior hypoglycemia were less likely to use SGLT2i, despite evidence supporting their preferential use in these patients. Efforts to address this treatment-risk paradox may help improve health outcomes among patients with type 2 diabetes.

Abstract Rationale Since their approval, there has been no real-world or randomized trial evidence evaluating the effect of the antifibrotic medications pirfenidone and nintedanib on clinically important outcomes such as mortality and hospitalizations. Objectives To evaluate the clinical effectiveness of the antifibrotic medications pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis. Methods Using a large U.S. insurance database, we identified 8,098 patients with idiopathic pulmonary fibrosis between October 1, 2014 and March 1, 2018. A one-to-one propensity score–matched cohort was created to compare patients treated with antifibrotic medications (n = 1,255) with those not on treatment (n = 1,255). The primary outcome was all-cause mortality. The secondary outcome was acute hospitalizations. Subgroup analyses were performed to evaluate mortality differences by drug. Measurements and Main Results The use of antifibrotic medications was associated with a decreased risk of all-cause mortality (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.62–0.98; P value = 0.034). However, this association was present only through the first 2 years of treatment. There was also a decrease in acute hospitalizations in the treated cohort (HR, 0.70; 95% CI, 0.61–0.80; P value &lt;0.001). There was no significant difference in all-cause mortality between patients receiving pirfenidone and those on nintedanib (HR, 1.14; 95% CI, 0.79–1.65; P = 0.471). Conclusions Among patients with idiopathic pulmonary fibrosis, antifibrotic agents may be associated with a lower risk of all-cause mortality and hospitalization compared with no treatment. Future research should test the hypothesis that these treatments reduce early, but not long-term, mortality as demonstrated in our study.