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The US veteran population has a high proportion of chronic lymphocytic leukemia (CLL) risk factors. Using the Veterans Health Administration (VHA) population, we conducted a retrospective chart review of 1205 CLL patients who initiated treatment with a novel oral agent. For 1L ibrutinib, 33% (n = 107) discontinued therapy during the study, of which 64% discontinued due to adverse events (AEs). For relapsed/refractory (R/R) ibrutinib, 35% (n = 262) discontinued therapy, of which 63% discontinued due to AEs. For R/R venetoclax, 31% (n = 27) discontinued therapy, of which 41% were due to AEs. For idelalisib, 84% (n = 41) discontinued therapy, of which 54% were due to AEs. This real-world study suggests that AEs play an important role in dose reductions and discontinuations; however, physician inexperience in using these drugs when they were first introduced could be part of what is leading to these negative outcomes.

BACKGROUND: The primary objective of emergency medicine (EM) residency training is to develop knowledgeable, procedurally competent, and highly efficient physicians. We aimed to determine current overall productivity statistics and if there is an average rate of productivity change for individual residents as they progress through their training. METHODS: This was a retrospective review of EM resident productivity performed at two American Council of Graduate Medical Education–accredited, community‐academic residency programs from July 2012 to June 2018. Productivity was defined by relative value units (RVU)/h, RVU/patient, and patients/h. Mixed‐effects models for repeated‐measures data were used to assess change in outcome over postgraduate year (PGY) levels. The models included the interaction between progressive PGY levels to assess whether there was a pattern of change between each training year. RESULTS: A total of 102 unique EM residents were included in the analysis. All three productivity measures increased linearly between PGY levels. However, while each graduating class had linear improvement throughout training, the rates of change were not consistent from one class to the next. Furthermore, a consistent rate of change between PGY for individual residents could not be established. Productivity can increase, decrease, stay the same, or any combination as residents advance through their training. CONCLUSIONS: Overall productivity of EM residents increases as they advance through their training. However, there is no consistent pattern of increase from one graduating class to the next and no reliable pattern of change for individual residents. Having increased granularity and understanding of productivity as it relates to individual residents will allow for more enhanced advisement of residents about their current productivity and their anticipated course through residency.

252 Background: Previously, we reported that adverse events (AEs) were the top reason for dose reductions in VHA patients on novel agents. Some AEs might be problematic but might not directly lead to dose reduction; however, these concomitant AEs should not be overlooked. This study describes AE clusters that occurred with the primary AE that led to dose reduction in VHA CLL patients receiving ibrutinib. Methods: This is a retrospective chart review study of CLL patients treated with ibrutinib in the VHA from October 2013 to March 2018. Variables included the presence of dose reduction, the reasons for dose reduction, primary AEs leading to dose reduction, and concomitant AEs present at the time of dose reduction. Descriptive statistics were used to summarize AE clusters. Results: Out of 1069 CLL patients on ibrutinib, 285 patients experienced dose reduction due to AEs and were included in this analysis. The most common AEs leading to dose reduction were: musculoskeletal (11%), bleeding (11%), fatigue (10%), infection (9%), atrial fibrillation (8%), diarrhea (8%), and rash (8%). Fatigue was the leading concomitant AE present at dose reduction among patients who were dose reduced due to musculoskeletal (18%), infection (12%), diarrhea (18%), and rash (25%). Fatigue was also the second-leading or third leading concomitant AE among those who were dose reduced due to atrial fibrillation (13%) or bleeding (10%). Musculoskeletal was the leading or second-leading concomitant AE present at dose reduction among those who were dose reduced due to fatigue (17%), infection (12%), or diarrhea (14%). Bleeding was the leading concomitant AE among those who were dose reduced due to atrial fibrillation (17%) and vice versa. Conclusions: This study provides evidence that fatigue and musculoskeletal AEs are problematic in CLL patients on ibrutinib in the VHA. These were not only among the most common primary AEs but also the leading concomitant AEs present at dose reduction. Although not directly leading to dose reduction, these ‘nuisance’ AEs can greatly affect quality of life among CLL patients and warrant more attention from clinicians. A better understanding of all AEs present at dose reduction may help clinicians better manage patients on novel agents. These data also highlight the unmet need for novel agents with a ‘cleaner’ safety profile.

e19339 Background: The first novel agent for use in CLL was approved in 2014; however, the extent of novel agent uptake in the VHA is largely unknown. Objective: This study described the pharmacoepidemiology of three novel agents (ibrutinib, idelalisib, venetoclax), and traditional chemotherapies/chemoimmunotherapies (CT/CIT) in the VHA. Methods: This was a retrospective study of 26,879 adults with CLL in the VHA from 10/01/2013 to 5/31/2018. All were followed for at least 6 months. Data were extracted from the VHA electronic health record. Patients came from all 18 Veterans Integrated Service Networks, spanning all 50 states and US territories. Descriptive statistics were used to summarize baseline characteristics, CLL treatments, next therapies, and secondary complications. Results: A total of 3670 patients received at least one of 12 CLL therapies of interest. Patients had a median age of 69 years (47% were 65+ and 26% were 75+), a median age-adjusted Charlson comorbidity score of 6, and 6% had a history of exposure to Agent Orange. Ibrutinib accounted for 89% of the novel agent use. Ibrutinib use across all lines of therapy (LOTs) increased sevenfold over the study period (Table). Venetoclax (42%) and idelalisib (30%) were the most common therapies for the next LOT after ibrutinib. Across all LOTs, traditional CT/CIT use declined steadily over the study period. However, in fiscal year (FY) 2018, there were still 17% of patients receiving CT/CIT. Ibrutinib was the most common therapy for the next LOT in these patients (43–74%). Incidence of diffuse large B cell lymphoma post-index was 2–6 times higher in patients on CT/CIT than those on ibrutinib. Other secondary complications were similar between ibrutinib and CT/CIT. Conclusions: To our knowledge, this is the largest study looking at CLL treatment patterns among VHA patients in the real world. There has been a major shift in the treatment of CLL, with fast adoption of novel agents in the VHA from 2013 to 2018. The impact of this shift on healthcare resource use and cost burden in the VHA will need to be examined. [Table: see text]

Introduction : CLL is the most common chronic leukemia in the US, with nearly 20,000 new cases expected annually. Novel agents, such as ibrutinib, idelalisib, and venetoclax, have been approved in recent years and provide oral options for CLL. However, there is limited data regarding real-world treatment patterns with these novel agents. This study describes dose reduction and discontinuation rates, reasons for both, and outcomes, including overall survival (OS) and duration of therapy (DOT), in CLL patients treated with novel agents. Methods : This is an analysis of a large retrospective cohort study of adult patients (≥ 18 years old) with CLL, treated with novel agents in the VHA from 10/01/2013 to 3/31/2018. Historical data were examined for up to 20 years prior to the enrollment period (10/01/1993 to 9/30/2013). Index date was defined as the date of novel agent initiation. The follow-up period was a minimum of 6 months post index date. Variables, collected via a structured EMR database, included patient demographics, and clinical and treatment characteristics. CLL diagnosis, molecular profiles, and reasons for dose reduction and discontinuation were abstracted by chart review. Descriptive statistics were used to summarize baseline characteristics, treatment patterns, and outcomes. Results: A total of 1205 CLL patients were included in this analysis. Of these, in first observed line, 328 (27%) patients received ibrutinib; in relapsed/refractory observed line (r/r), 741(62%) patients received ibrutinib, 49 (4%) patients on idelalisib, and 87 (7%) patients on venetoclax. Ibrutinib patients in first observed line had a median (range) age of 73 (48-96) years and a median follow-up of 23 (3-54) months after treatment initiation. Dose reduction (n=83, 25%) and discontinuation (n=108, 33%) were frequently due to adverse events (AEs) (93% and 64%). Median DOT to ibrutinib discontinuation was 8 months. The most common AEs leading to dose reduction were major bleed (15%) and rash (15%). The most common AEs leading to discontinuation were atrial fibrillation (20%), major bleed (19%), and infection (11%). The calculated median OS from initiation was 31 (14-49) months. R/R ibrutinib patients had a median age of 72 (45-96) years and had 31 (2-85) months of follow-up after treatment initiation. Dose reduction (n=242, 33%) and discontinuation (n=263, 35%) were frequently due to AEs (89% and 63%). Median DOT to ibrutinib discontinuation was 12 months. The most common AEs leading to dose reduction were thrombocytopenia (13%), arthralgia/myalgia (13%), and infection (12%). The most common AEs leading to discontinuation were atrial fibrillation (19%), infection (15%), and major bleed (11%). the calculated median OS from initiation was 39 (9-57) months. R/R idelalisib patients (n=49) had a median age of 72 (55-93) years and had 27 (3-53) months of follow-up after treatment initiation. Dose reduction (n=8, 16%) and discontinuation (n=41, 84%) were frequently due to AEs (100% and 54%). Median DOT to idelalisib discontinuation was 5 months. The most common AE leading to dose reduction was neutropenia (50%). The most common AEs leading to discontinuation were infection (27%) and pneumonia (18%). R/R venetoclax patients (n=87) had a median age of 72 (47-90) years and had 9 (0-35) months of follow-up after treatment initiation. Dose reduction (n=24, 28%) and discontinuation (n=27, 31%) were frequently due to AEs (100% and 41%). Median DOT to venetoclax discontinuation was 5 months. The most common AEs leading to dose reduction were neutropenia (27%) and thrombocytopenia (27%). The most common AEs leading to discontinuation were neutropenia (36%), thrombocytopenia (18%), and infection (18%). There was not enough follow-up time to have a meaningful OS in this cohort. Conclusions: To our knowledge, this is the largest EMR/chart review study among CLL patients initiating treatments in the real-world setting. This study provides evidence regarding patient characteristics, treatment patterns, and outcomes among patients initiating novel agents for the treatment of CLL in the national VHA population. Dose reduction and discontinuation were frequent across all novel agents, with AEs as the most common reason. These data highlight the significant difference in real world data compared with clinical trial data and indicate the unmet need for more tolerable treatment options for CLL patients. Disclosures Frei: AstraZeneca: Research Funding. Le:AstraZeneca: Employment, Other: Stocks. McHugh:AstraZeneca: Employment. Elesinmogun:AstraZeneca: Employment, Equity Ownership. Obodozie-Ofoegbu:UT Austin: Employment.

The increasing complexity of cancer chemotherapy increases the requirement that pharmacists be familiar with these highly toxic agents. This column will review various issues related to preparation, dispensing, and administration of cancer chemotherapy, and review various agents, both commercially available and investigational, used to treat malignant diseases. Questions or suggestions for topics should be addressed to Dominic A. Solimando, Jr., President, Oncology Pharmacy Services, Inc., 4201 Wilson Blvd #110-545, Arlington, VA 22203, e-mail: OncRxSvc@aol.com ; or J. Aubrey Waddell, Associate Professor, University of Tennessee College of Pharmacy; Oncology Pharmacist, Pharmacy Department, Blount Memorial Hospital, 907 E. Lamar Alexander Parkway, Maryville, TN 37804, e-mail: waddfour@charter.net .

An ultimate goal in the development of effective rehabilitation interventions within clinical-research contexts is the dissemination of these techniques to the “typical” treatment setting. Often however, hospital administrators at such settings either see this goal as unattainable, or do not implement a carefully integrated process of staff training and administrative support. In this paper, we describe the steps in an ongoing effort to implement psychiatric rehabilitation practices hospital-wide in a state psychiatric facility. This process has involved a number of critical components including time-limited use of outside experts, focused administrative support and quality assurance, continuing education opportunities, and the establishment of both a unit specializing in rehabilitation interventions that serves as an ongoing training environment for hospital staff, and a core group of practitioners from this program who provide regular external consultation to other hospital programs. These and ...

BACKGROUND There is little information for age differences in body composition in elderly people > 65 years of age, especially for those > 80 years. As the proportion of people older than 65 years is expected to nearly double during the next few decades, this information is needed. METHODS Age differences in body composition and anthropometry were examined in 316 men and women aged 60 to 95 years. Multiple components of body composition were quantified using dual energy X-ray absorptiometry and isotope dilution methods, and expressed in molecular and cellular models. Analysis of variance was used to test for differences between age groups 60 to 70, 71 to 80, and > 80 years in each sex. Body composition components were regressed on age, controlling for knee height, fat-free mass, or total body fat. Age-adjusted correlations were calculated with anthropometric variables. RESULTS Fat-free mass (FFM), body cell mass (BCM), and appendicular skeletal muscle (ASM) decreased with age in both sexes. ASM decreased relative to FFM in both the men and the women, while BCM decreased relative to FFM in the women only. Total fat mass and percent body fat decreased with age in the women, but not in the men. Body fat distribution did not appear to change with age. Anthropometric indices, muscle area and waist/hip ratio, had low correlations with muscle mass and fat distribution. CONCLUSIONS "Sarcopenia," or muscle loss, continues to occur into old age, and may have significant impacts on physical function and health status. New anthropometric techniques are needed for assessing muscle loss with age.

There is little, if any, information on bone mineral densities (BMD) in Native Americans. This information is valuable not only for assessing the risk of osteoporosis and fractures in this population, but with regard to estimating levels of obesity (%body fat), since bone mineral is a major factor influencing the density of the fat-free mass.1