ALBERT

Description: Introduction: Febrile neutropenia and hospitalizations for infection are serious potential complications of myelosuppressive chemotherapy treatment in cancer patients. Oral antimicrobial use may provide effective prophylaxis against these complications in the elderly population. The available literature provides a limited description of antimicrobial use in elderly patients with non-Hodgkin lymphoma (NHL) receiving chemotherapy. Objectives: Describe the use patterns of oral antimicrobial agents in elderly patients with NHL on chemotherapy. Methods: The study population included non-HMO enrollees in the 20% Medicare sample with Parts A, B, and D coverage who had NHL and initiated their first course of chemotherapy between July 1, 2007, and November 30, 2011. We searched Part D claims for oral antimicrobial agents from 5 days before chemotherapy initiation to the end of the first cycle. We examined type of antimicrobial agents prescribed and timing of first prescription fill relative to chemotherapy initiation. Counts and percentages were estimated. Results: The study cohort included 6306 patients with NHL; 1682 patients (26.7%) had at least one prescription fill for an oral antimicrobial agent during the first cycle, for an overall total of 2569 claims for antimicrobials. Of these, 77.1% were for antibacterial, 9.9% for antifungal, and 13.1% for antiviral agents. Of antibacterial claims, 44.3% were for fluoroquinolones, 16.2% for sulfonamides, 12.0% for penicillins, and 12.0% for cephalosporins. First prescription fill occurred in the 5 days before the start of the first cycle for 17.4% of patients, from day 0 (the beginning of the cycle) to day 5 for 22.9%, and from day 6 to the end of the cycle for 59.7%. Peak days for first prescription fill were days 0, 7, and 14 of the first chemotherapy cycle (Figure). Conclusions: Over 25% of elderly NHL patients filled prescriptions for oral antimicrobial agents during the first cycle of chemotherapy. Since these data represent the fill date and not the date a patient started taking the medicine, it is possible that all fills in the 5 days before day 0 were to be started on day 0. Under this assumption, about 26% of prescriptions were started at the beginning of the cycle, likely for prophylaxis, and the remaining (especially peaks on days 7 and 14) may reflect either prophylaxis or treatment for an active infection. The literature suggests that peak infection risk occurs between days 7 and 16 of the chemotherapy cycle.  Current antibiotic use patterns may not be optimal for patient care. Figure 1 Figure 1. Note: 114 patients had their first oral antimicrobial prescription fill after day 23, but these results could not be shown because there were fewer than 11 patients on each of those days. Disclosures Page: Amgen Inc.: Employment, Equity Ownership. Barron:Amgen Inc.: Employment, Equity Ownership. Morrow:Amgen Inc.: Employment, Equity Ownership. Stryker:Amgen Inc.: Employment, Equity Ownership. Acquavella:Amgen Inc.: Employment, Equity Ownership. Collins:ZS Pharma Inc.: Consultancy; Keryx Biopharmaceuticals, Inc.: Consultancy; Amgen Inc.: Consultancy; NxStage Medical Inc.: Consultancy.

Description: Background: Febrile neutropenia (FN) and hospitalizations for infection are serious potential complications of myelosuppressive chemotherapy (chemo) treatment in cancer patients. Primary prophylactic G-CSF (PPG) is often used to decrease incidence of FN in patients at high risk. Due to the potential for G-CSF to stimulate neutrophil precursors at the same time as myelosuppression from chemotherapy, it is recommended that G-C SF be administered 24 hours after chemo administration. In addition, several studies showed that use of G-CSF on the same day as chemo may result in worse FN outcomes. Data are limited describing practice patterns of PPG timing relative to chemo administration in elderly patients with non-Hodgkin's lymphoma (NHL), overall and by agent. Methods: The study population included non-HMO enrollees in the 20% Medicare sample with Parts A and B coverage who had NHL and initiated the first course of chemo between July 1, 2007, and November 30, 2011. PPG was defined as G-CSF initiated during days 0-5 of the first cycle, with day 0 the start of the chemo course. In patients with PPG, type of agent prescribed [Filgrastim (FIL), Sargramostim (SAR), or Pegfilgrastim(PEG)], timing of PPG initiation relative to chemo start date overall and by agent, and duration of prophylactic use (for the daily use agents FIL and SAR) were examined. Counts and percentages were estimated. Results: The study cohort included 13,402 patients with NHL; 2690 (20.1%) received PPG. In these patients, the most common PPG agent used was PEG (2471; 91.9%) followed by FIL (171; 6.4%) and SAR (48; 1.8%). The median [interquartile range] of course duration (in days) for the daily use agents was 3.5 [2, 5] for FIL and 3 [1.5, 5] for SAR. Overall, first G-CSF use within the prophylactic period peaked on the day after chemo initiation (day 1, 47.3%) and steadily decreased from day 2 (22%) to day 5 (4%). About 5% of patients received PPG on the same day as chemo (day 0). Patterns were similar by agent type (Figure). More PPG with FIL than with PEG was used on days 4 and 5. Conclusion: Use of prophylactic growth factor support is the recommended standard of care for patients at high risk of neutropenic infection. Consistent with the recommendations, PPG began most often on the day after chemo initiation regardless of agent type and more PPG with FIL started on day 4 or 5 after chemo initiation. Figure 1 Figure 1. Note: Ten or fewer patients with SAR on days 0, 3-5. Results are not shown. Disclosures Page: Amgen Inc.: Employment, Equity Ownership. Barron:Amgen Inc.: Employment, Equity Ownership. Morrow:Amgen Inc.: Employment, Equity Ownership. Stryker:Amgen Inc.: Employment, Equity Ownership. Acquavella:Amgen Inc.: Employment, Equity Ownership. Collins:ZS Pharma Inc.: Consultancy; Keryx Biopharmaceuticals, Inc.: Consultancy; Amgen Inc.: Consultancy; NxStage Medical Inc.: Consultancy.

Description: Abstract 2187 Introduction: A recent systematic review and meta-analysis of randomized controlled trials of thrombopoietin-receptor agonists (TPOr), romiplostim and eltrombopag, in adult thrombocytopenic patients found a numerically but non-statistically significant increase in the occurrence of thromboembolism (TE) among treated patients compared to those not treated with TPOr.1 To put these results into context and to estimate the baseline risk of TE in ITP patients, this study will summarize results of observational studies that reported the risk of venous thrombembolism (VTE) or arterial thrombembolism (ATE) in patients with ITP relative to comparable populations without ITP. Methods: We searched MEDLINE and EMBASE via Ovid and the Cochrane database for articles that included both terms relating to ITP (i.e., immune thrombocytopenia, idiopathic thrombocytopenia) and TE (i.e., thromboembolism, thrombosis, embolism). Articles were restricted to research on humans, published in English, January 1996 to July 2012. Only observational studies were included. We abstracted measures of relative risk (or rate ratio) comparing the incidence of TE in ITP patients with that in a comparable non-ITP population. The pooled relative risk and 95% confidence intervals (CIs) were calculated by taking a weighted average of individual study results using both fixed and random effects models using the META2 module for STATA 10. Results: Five observational studies met the inclusion criteria: two from Denmark and one each from Sweden, United Kingdom, and United States; all published 2010–2012. All studies completed patient follow-up before the commercial availability of TPOr. Studies varied in the duration of follow-up, choice of comparison group, and specific events reported. Some studies excluded patients with previous events. The relative risk of any VTE among patients with ITP compared to that in a non-ITP population ranged from 1.6 to 2.9 based on 3 studies that reported VTE. The pooled relative risk of any VTE was 1.9 (95%CI 1.4, 2.7) using a fixed-effect model and similar estimates using a random effect model (test for heterogeneity, p = 0.3). The relative risk of any ATE among patients with ITP compared to that in a non-ITP population ranged from 1.3 to 1.6 based on 3 studies that reported ATE. The pooled relative risk of any ATE was 1.5 (95%CI 1.3, 1.8) for both the random and fixed effects models (test for heterogeneity, p = 0.7). Conclusions: Five population-based observational studies have been published recently comparing the risk of thrombembolism among ITP patients to populations without ITP. The results of a meta-analysis showed nearly a 2-fold increased risk of VTE and a 50% increased risk of ATE among the general population of ITP patients not treated with TPOr. These ITP patients were likely to have less severe disease than those in experimental trials where entrance criteria may require significant thrombocytopenia, prior bleeding episodes, or failure of a previous therapy. However, the demonstrated elevated risk of TE among patients with ITP should be considered when evaluating the risk of TE ascribed to ITP treatments. Disclosures: Langeberg: Amgen: Employment, Equity Ownership. Eisen:Amgen: Employment, Equity Ownership. Schoonen:Amgen: Employment, Equity Ownership. Gamelin:Amgen: Employment, Equity Ownership. Stryker:Amgen: Employment, Equity Ownership.

Description: Background: ITP is a rare autoimmune disorder characterized by low platelet counts, resulting in an increased risk for bleeding. Paradoxically, patients with cITP may also have an increased incidence of thrombotic or thromboembolic events, but population-based data on this are limited. We estimated the incidence of these events in a prospective cohort study of incident cITP patients in three Nordic countries. Methods: Based on National Health Registry Systems (NHRSs) and medical records in Denmark, Norway, and Sweden, the study cohort included all adults diagnosed with cITP from January 1, 2008 to December 31, 2012 (n=1,821). Arterial thrombotic events (myocardial infarction [MI] and stroke) and venous thromboembolic events (pulmonary embolism and deep vein thrombosis) were identified in the NHRSs. Patients were followed from the latest of cITP diagnosis or April 1, 2009, until the earliest date of the first occurrence of the event of interest, death, emigration, or December 31, 2012. Incidence rates (events per 1,000 person-weeks [PW]) were computed for the entire cohort and stratified by gender, age, splenectomy status, and comorbidity burden. Results: Nearly 60% of the cITP cohort was 〉50 years in age, and 56% were female. Overall, the incidence of arterial thrombotic events was 0.31 per 1,000 PW (95% confidence interval [CI]: 0.25-0.39) and the incidence of venous thromboembolic events was 0.18 per 1,000 PW (95% CI: 0.13-0.24). For arterial thrombotic events, the risk was higher in males (compared with females), and the risk for both event types increased with increasing age and comorbid burden. Given the small number of patients who underwent splenectomy (n=101), it was difficult to detect any differences in the risk of thrombotic events by splenectomy status, but the incidence of venous thromboembolic events was higher in splenectomized versus non-splenectomized patients (0.27 per 1,000 PW [95% CI: 0.15-0.50] versus 0.16 [95% CI: 0.11-0.23]). Conclusions: Among patients with cITP, the risk of arterial thrombotic events is higher in males than females and increases with increasing age and level of comorbid burden. The risk of venous thromboembolic events is heightened in cITP patients who have undergone splenectomy. Abstract 4845. TableArterial thrombotic eventsVenous thromboembolic eventsN / PWIncidence rate per 1,000 PW (95% CI)N / PWIncidence rate per 1,000 PW (95% CI)Overall (n=1,821)68 / 218,3910.31 (0.25-0.39)39 / 220,8650.18 (0.13-0.24)GenderMale (n=794)39 / 90,5310.43 (0.31-0.59)17 / 92,4080.18 (0.11-0.30)Female (n=1,027)29 / 127,8600.23 (0.16-0.33)22 / 128,4570.17 (0.11-0.26)Age18-50 years (n=751)5 / 96,1190.05 (0.02-0.12)5 / 95,9630.05 (0.02-0.13)51-70 years (n=544)13 / 65,6520.20 (0.11-0.34)13 / 65,5560.20 (0.12-0.34)〉70 years (n=526)50 / 56,6210.88 (0.67-1.17)21 / 59,3450.35 (0.23-0.54)Comorbid burdenLow (n=1,243)25 / 154,1810.16 (0.11-0.24)18 / 155,0580.12 (0.07-0.18)Moderate (n=435)29 / 48,3070.60 (0.42-0.86)14 / 49,6940.28 (0.17-0.48)High (n=143)14 / 15,9030.88 (0.52-1.49)7 / 16,1130.43 (0.21-0.91)Splenectomy statusSplenectomized (n=101)10 / 37,1210.27 (0.14-0.50)10 / 36,9570.27 (0.15-0.50)Non-splenectomized (n=1,720)58 / 181,2700.32 (0.25-0.41)29 / 183,9080.16 (0.11-0.23) Disclosures Cetin: Amgen: Employment. Ghanima:Roche: Consultancy, Research Funding; Amgen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy. Stryker:Amgen Inc.: Employment, Equity Ownership.

Description: An observational study was conducted at 18 transplant centers in the United States and Canada to characterize the platelet recovery of patients receiving myeloablative therapy and stem cell transplantation and to determine the clinical variables influencing recovery, determine platelet utilization and cost, and incidence of hemorrhagic events. The study included 789 evaluable patients transplanted in 1995. Clinical, laboratory, and outcome data were obtained from the medical records. Variables associated with accelerated recovery in multivariate models included (1) higher CD34 count; (2) higher platelet count at the start of myeloablative therapy; (3) graft from an HLA-identical sibling donor; and (4) prior stem cell transplant. Variables associated with delayed recovery were (1) prior radiation therapy; (2) posttransplant fever; (3) hepatic veno-occlusive disease; and (4) use of posttransplant growth factors. Disease type also influenced recovery. Recipients of peripheral blood stem cells (PBSC) had faster recovery and fewer platelet transfusion days than recipients of bone marrow (BM). The estimated average 60-day platelet transfusion cost per patient was $4,000 for autologous PBSC and $11,000 for allogeneic BM transplants. It was found that 11% of all patients had a significant hemorrhagic event during the first 60 days posttransplant, contributing to death in 2% of patients. In conclusion, clinical variables influencing platelet recovery should be considered in the design and interpretation of clinical strategies to accelerate recovery. Enhancing platelet recovery is not likely to have a significant impact on 60-day mortality but could significantly decrease health care costs and potentially improve patient quality of life.

Description: An observational study was conducted at 18 transplant centers in the United States and Canada to characterize the platelet recovery of patients receiving myeloablative therapy and stem cell transplantation and to determine the clinical variables influencing recovery, determine platelet utilization and cost, and incidence of hemorrhagic events. The study included 789 evaluable patients transplanted in 1995. Clinical, laboratory, and outcome data were obtained from the medical records. Variables associated with accelerated recovery in multivariate models included (1) higher CD34 count; (2) higher platelet count at the start of myeloablative therapy; (3) graft from an HLA-identical sibling donor; and (4) prior stem cell transplant. Variables associated with delayed recovery were (1) prior radiation therapy; (2) posttransplant fever; (3) hepatic veno-occlusive disease; and (4) use of posttransplant growth factors. Disease type also influenced recovery. Recipients of peripheral blood stem cells (PBSC) had faster recovery and fewer platelet transfusion days than recipients of bone marrow (BM). The estimated average 60-day platelet transfusion cost per patient was $4,000 for autologous PBSC and $11,000 for allogeneic BM transplants. It was found that 11% of all patients had a significant hemorrhagic event during the first 60 days posttransplant, contributing to death in 2% of patients. In conclusion, clinical variables influencing platelet recovery should be considered in the design and interpretation of clinical strategies to accelerate recovery. Enhancing platelet recovery is not likely to have a significant impact on 60-day mortality but could significantly decrease health care costs and potentially improve patient quality of life.