Use Of Filgrastim Research Articles

Filgrastim use in patients receiving chemotherapy for early-stage breast cancer—a survey of physicians and patients

Despite its widespread use as primary febrile neutropenia (FN) prophylaxis during chemotherapy for early-stage breast cancer, the optimal duration of daily filgrastim is unknown. Using the minimum effective duration may improve patient comfort and acceptability while reducing costs. Yet, suboptimal dosing may also negatively impact patient care. A survey was performed to obtain information regarding current practices for granulocyte colony-stimulating factor (G-CSF) use. Canadian oncologists involved in the treatment of breast cancer patients, as well as patients who had received neo/adjuvant chemotherapy for breast cancer, were surveyed. Standardized surveys were designed to collect information on perceived reasons for G-CSF use and current practices. The surveys were completed by 38/50 (76%) physicians and 95/97 (98%) patients. For physicians, there was variability in the choice of chemotherapy regimens that required G-CSF support, the dose of filgrastim prescribed and the number of days prescribed. The majority of physicians reported using 5 (31.6%), 7 (47.4%), or 10 (13.2%) days of therapy. Nearly half of the patients (46.3%) recalled having experienced at least one of the chemotherapy-related complications including chemotherapy delays, dose reductions, and FN. While on filgrastim, 66.3% of patients reported myalgia and bone pain. Both physicians and patients expressed interest in participating in clinical trials designed to optimize the duration of filgrastim administration. Significant variability in practice exists with respect to filgrastim administration. Definitive studies are therefore required to standardize and improve care, as this has the potential to impact treatment outcomes, patient quality of life, and cost savings.

Conversion from Filgrastim to Tbo-filgrastim: Experience of a Large Health Care System.

In 2008, tbo-filgrastim was approved as a biosimilar in Europe and then approved in the United States by the FDA in 2012 as a biologic product with 1 similar indication to filgrastim. Because tbo-filgrastim was less expensive than filgrastim, and clinical information and expert opinion supported similarity, the Pharmacy & Therapeutics Committee of a large health care system approved tbo-filgrastim as the preferred granulocyte-colony stimulating factor (G-CSF) product in March 2014. To (a) assess the use of filgrastim and tbo-filgrastim products by comparing baseline characteristics, setting of care, indication for use, and payer type and (b) understand potential barriers of conversion to tbo-filgrastim. A retrospective evaluation of filgrastim and tbo-filgrastim use was conducted on all patients (N = 204) who received the drugs between July 2015 and December 2015 at the 2 largest hospitals in the health system. Baseline characteristics, indication requiring use of filgrastim or tbo-filgrastim, setting of care, and payer information were collected from electronic medical records, and descriptive analyses were conducted. Overall, G-CSFs were administered to 204 patients for 261 episodes of care (filgrastim and tbo-filgrastim were used in 65 and 196 episodes of care, respectively). Baseline characteristics were similar between the 59 patients who received filgrastim and the 174 patients who received tbo-filgrastim. G-CSF was primarily used in the inpatient setting (163 episodes of care, 63%) with 90% of patients using tbo-filgrastim. In the outpatient setting (98 episodes of care, 38%), filgrastim and tbo-filgrastim were each used by 50% of patients. Tbo-filgrastim was the preferred G-CSF by clinical providers for all indications, except for stem cell mobilization, where filgrastim use was higher (55% vs. 45% of 71 episodes of care). In the outpatient setting, analysis by payers showed that the majority of patients on commercial plans were using filgrastim (58%), while half of Medicare patients were using filgrastim (50%, n = 12). Twelve patients were self-paid, and all were using tbo-filgrastim. Subgroup analysis by hospital showed differences in utilization patterns. Although tbo-filgrastim was the preferred G-CSF in our formulary, 29% of patients continued to receive filgrastim. Conversion to tbo-filgrastim has been largely successful, but extra steps may be needed to achieve full conversion to biosimilars. No outside funding supported this study. Agboola was employed by Partners Healthcare at the time of the study. The authors have nothing to disclose. Study concept and design were contributed equally by Agboola and Reddy. Agboola collected the data, and data interpretation was performed by both authors. The manuscript was written primarily by Agboola, with assistance from Reddy. Both authors revised the manuscript.

Evaluation of Filgrastim Therapy in Kidney Transplant Recipients.

Neutropenia is associated with a high risk of serious infections in kidney transplant recipients. There are no sufficient studies of using granulocyte colony-stimulating factors, such as filgrastim, in renal transplant recipients to establish a clear, specified role of this off-label indication. Using filgrastim in these patients may increase the risk of rejection by overstimulating the immune system. To evaluate the use of filgrastim in adult kidney transplant recipients presenting with neutropenia. Data were obtained from a medication utilization report of filgrastim in kidney transplant recipients at our center from September 2012 to August 2015. Main Outcome Measure(s) and Results: There were 28 cases of neutropenia that were treated with a range of 1 to 5 doses of filgrastim 300 or 480 μg, with a mean of 1.79 doses. The mean total dose of filgrastim administered per episode of neutropenia was 632 μg (8.6 μg/kg). Overall, 87.5% of the cases achieved a white blood cell count of at least 3 × 109 cells/L within 7 days of hospital discharge. There were no cases of infection or acute rejection following treatment. The use of filgrastim in kidney transplant recipients demonstrated success in reversing neutropenia. Short courses of therapy were required with minimal adverse events. Patients who required readmission were successfully re-treated. Additional studies are required to determine the most effective dose and duration of treatment.

Use of granulocyte-colony stimulating factor to prevent recurrent clozapine-induced neutropenia on drug rechallenge: A systematic review of the literature and clinical recommendations.

Clozapine is the most effective medication for treatment-refractory schizophrenia; however, its use is contraindicated in people who have had previous clozapine-induced neutropenia. Co-prescription of granulocyte-colony stimulating factor may prevent recurrent neutropenia and allow continuation or rechallenge of clozapine. Systematic review of literature reporting the use of granulocyte-colony stimulating factor to allow rechallenge or continuation of clozapine in people with previous episodes of clozapine-induced neutropenia. The efficacy of granulocyte-colony stimulating factor and predictors of successful rechallenge will be determined to elucidate whether evidence-based recommendations can be made regarding the use of granulocyte-colony stimulating factor in this context. A total of 17 articles were identified that reported on clozapine rechallenge with granulocyte-colony stimulating factor support. In all, 76% of cases were able to continue clozapine at median follow-up of 12 months. There were no clear clinical or laboratory predictors of successful rechallenge; however, initial neutropenia was more severe in successful cases compared to unsuccessful cases. Cases co-prescribed lithium had lower success rates of rechallenge (60%) compared to those who were not prescribed lithium (81%). The most commonly reported rechallenge strategy was use of filgrastim 150-480 µg between daily to three times a week. There were no medication-specific side effects of granulocyte-colony stimulating factor reported apart from euphoria in one case. Three cases who failed granulocyte-colony stimulating factor had bacterial infection at time of recurrent neutropenia. No deaths were reported. Preliminary data suggest granulocyte-colony stimulating factor is safe and effective in facilitating rechallenge with clozapine. Clinical recommendations for use are discussed.

Efficacy and safety of biosimilar filgrastim in primary and secondary prevention of febrile neutropenia.

Neutropenia and febrile neutropenia (FN) are among the most common side effects/complications of chemotherapy. The aim of the present study was to evaluate the practice of the use of biosimilar filgrastim in the primary and secondary prevention of FN, and assess its efficacy and safety. A multi-center, non-interventional epidemiological study of 170 cancer patients aged 23-82 years was conducted. Data were collected via a questionnaire completed based on medical documentation and patient examination over five chemotherapy visits. The risk of FN related to the chemotherapy protocol used was in the range of 10-20% in >50% of the patients (53.5%) and a majority (74.7%) had additional FN risk factors. 60% of the patients received filgrastim as primary prevention of FN, and 40% received it as secondary prevention. In 40.6% of cases, six cycles of chemotherapy were used. More than 90% of patients continued chemotherapy according to the initial recommended dose. In majority of patients, no FN was observed following the final cycle of chemotherapy. Median neutrophil count at visit 1 was 2.2×103/µl and did not fall below that level. Majority of patients (>70%) performed self-injections of filgrastim, and 86.3% of patients were continuing therapy with this drug at the last visit. No treatment-related side effects were recorded. The use of biosimilar filgrastim in the primary and secondary prevention of FN allows to maintain initial chemotherapy dosage. Furthermore, the use of biosimilar filgrastim is safe and tolerable, and has a high acceptance by patients.

Therapeutic Use of Filgrastim for Established Febrile Neutropenia Is Cost Effective Among Patients With Solid Tumors and Lymphomas

PurposeWith the emergence of biosimilar filgrastim to the market, there is a gradual decrease in the listed price of the originator product of filgrastim over the years, and this could have an impact on the cost-effectiveness of filgrastim in the treatment of febrile neutropenia (FN). A cost-effectiveness analysis would allow clinicians to make informed decision when considering the therapeutic filgrastim among low-risk FN patients. This study aims to evaluate the cost-effectiveness of adding therapeutic filgrastim to antibiotics in the treatment of established FN among patients with solid tumors and lymphomas. MethodsA decision tree model was created to compare two treatment options for established FN as follows: (1) antibiotics alone (standard care) and (2) antibiotics with therapeutic filgrastim (comparator). The target population was a hypothetical cohort of adult cancer patients with solid tumors or lymphomas hospitalized with FN in Singapore. The analysis was performed from a hospital’s perspective over a 21-day time horizon. The main outcome measures included costs, quality-adjusted life year (QALY) and incremental cost-effectiveness ratio (ICER). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to evaluate the robustness of the results. FindingsCompared with antibiotics alone, the treatment strategy of antibiotics with therapeutic filgrastim was a dominant choice, incurring a cost saving of US$125 per patient (comparator versus standard care: US$9110 versus US$9235) and additional health benefit of 0.0007 QALY gained per patient (comparator versus standard care: 0.0450 versus 0.0443). Model results were robust against the parameter variations in the one-way sensitivity analyses, but increasing the cost of filgrastim beyond US$87 per injection would increase the ICER to >US$50,000/QALY. Furthermore, the strategy of antibiotics with therapeutic filgrastim was the preferred choice (dominant or cost-effective) in 83.7% of the model iterations at a willingness-to-pay threshold of US$50,000/QALY. ImplicationsFrom a hospital’s perspective, the therapeutic filgrastim, in conjunction with antibiotics, in the treatment of FN is cost effective. This provides evidence to support the routine use of filgrastim for the treatment of FN among adult cancer patients with solid tumors and lymphomas.

High-Dose Filgrastim Treatment of Nonregenerative Pancytopenia Associated With Chronic Canine Ehrlichiosis

To report the management and outcome of a dog with canine monocytic ehrlichiosis and nonregenerative pancytopenia, with high doses of filgrastim. An 8-year-old male, mixed-breed dog, weighing 5.6kg, presented with a 1-month history of hyporexia, adynamia, and a weight loss of approximately 1kg. The general condition of the dog was observed to be poor as follows: lethargy, tachycardia, marked pallor of the mucous membranes, petechiae on the abdomen, hepatosplenomegaly, and cervical lymphadenopathy. A complete blood count analysis revealed severe leukopenia, thrombocytopenia, and anemia. A direct immunofluorescence assay using anti-Ehrlichia canis-immunoglobin G (1:400) yielded positive result. The dog was diagnosed with nonregenerative pancytopenia associated with canine monocytic ehrlichiosis. The dog presented poor prognostic signs (neutropenia, thrombocytopenia, and severe anemia). The dog was treated with antibiotics and a short course of high-dose filgrastim (50µg/kg, SC, q 48h for 4 days) to stimulate bone marrow response, prednisone to decrease peripheral platelet destruction, and an iron supplement to compensate for the iron deficiency in the bone deposits. Although temporary side effects associated with filgrastim use, such as bone pain, bleeding, and the worsening of thrombocytopenia, were observed, the treatment improved the clinical course and the cell counts in less than a month. The treatment protocol used in this case might be an alternative for treating cases of severe myelosuppression. This treatment plan can substantially change the clinical course of the disease for the better, compared to conventional treatment.

Exciting Results with Injection Darbepoietin Alfa and Pegfilgrastim in Patients with Decompensated Liver Cirrhosis

1.1.Introduction: Dysregulated erythropoietin (EPO) plasma levels may play a role in the patho physiology of liver cirrhosis. No report of Darbepoetin alpha and Pegylated Filgrastim use in Liver cirrhosis. 1.2.Aims and methods:To study the benefits of Darbepoetin and Pegfilgrastim in patients with de-compensated liver cirrhosis. Prospectively clinical data recorded since October 2014. Patients with active bleed, hepato renal syndrome, hepatoma, portal vessel thrombosis were excluded. Patients started on Injection Darbepoetin alpha 200 microgram and Injection Pegfilgrastim 6 mg subcutaneously every 15 days, total three visits of patients, then three month follow up planned. Improvement in clinical, laboratory parameters analyzed. Median calculated, Wilcoxon Signed-Rank Test applied to compare both groups. 1.3.Results and discussion:N=22 all male, 3 lost to follow up, aetiology of cirrhosis were Non-alcoholic Fatty Liver Disease 5, Hepatitis B Virus 3, Hepatitis C Virus 2 and Alcohol 12. Median age 59 years (range: 40 to 70). Improvement in Haemoglobin from 10.1 gram% (range 5.9-13.4 gm%) to 10.6 gm % (range: 7.5-13.7 gm%) p value 0.00374, Total leukocyte count from 5100/cu mm to 7100/cu mm p value 0.00214, Platelet count 90,000/cu mm to 146,000/cu mm, p value 0.00096, INR 1.7 (range 1.5-4.8) to 1.4 p value 0.00064, Albumin 2.4 gram/dl (range 1.6-2.9) to 2.5 gm/dl (range 1.8-3.5) P value 0.043, Child score from 10 to 8 P value 0.007, ascites score 2 to 1, P value 0.00222. No significant improvement in Serum creatinine, sodium, potassium, calcium, bilirubin, total protein and hepatic encephalopathy. High cost of medicine was the limiting factor. 1.4.Conclusion:Our study suggests that Darbepoetin Alpha and Pegfilgrastim is significantly effective in improving hematology, International normalized ratio, Albumin, ascites and Child score of liver cirrhosis patients.

Pegfilgrastim Use and Risk of Bleomycin Induced Pulmonary Toxicity in Hodgkin Lymphoma

BackgroundHodgkin lymphoma (HL) is a potentially curable malignancy when treated with bleomycin-containing chemotherapy regimens such as ABVD at full dose intensity. Growth factor support may be necessary to maintain dose intensity. The major limitation of bleomycin use is the development of bleomycin induced pulmonary toxicity (BPT). Bleomycin-induced cell injury stimulates an inflammatory response n the lung. G-csf has been shown in animal models to augment this response. Clinically, filgrastim (g-csf) use appears to increase the risk of BPT in HL, with BPT occurring in 25.6% of ABVD treated pts who were exposed to filgrastim in one study1. It remains unclear whether pegylated filgrastim, with a delayed onset of action, also leads to increased BPT. We previously reported2 a small series of HL pts who were predominantly treated with pegfilgrastim with ABVD and did not find increased BPT. We now report an update of our experience, including a larger subset who did not receive pegfilgrastim.MethodsAll cases of HL diagnosed from 1/2004 to 2/2016 and treated at MetroHealth Medical Center, a safety net hospital in Cleveland, OH, were reviewed. Pts who did not receive bleomycin or received filgrastim were excluded. 69 cases were identified, all of whom were treated with ABVD. 34 of these patients (Group A) received pegfilgrastim (all at least 24 hours after bleomycin) while 35 (Group B) did not receive pegfilgrastim. BPT was defined by the presence of new pulmonary symptoms, radiographic findings of interstitial infiltrates and absence of infection.ResultsGroup A: mean age of 38 (19-73), stage I-2/34, II-17/34, III-6/34 and IV-9/34. 30 of 34 patients received full doses of ABVD, 2 of 34 patients received 4 cycles of ABVD followed by radiation therapy, one patient received ABD and one patient received ABVD with bleomycin on hold after 3 cycles due to lung toxicity. Complete remission (CR) was found in 27 of 34 patients, partial remission (PR) was identified in 5 of 34 patients and response was unavailable in the remaining 2 patients. 3/34 pts developed relapse of HL. Of 34 patients, one (2.9%) developed BPT (age 44).Group B: mean age of 37 (22-69), stage II-18/35, III-11/35 and IV-6/35, 26 of 35 patients received full doses of ABVD and 4 of those were given radiation therapy. 2 patients had bleomycin held due to pulmonary toxicity. CR was identified in 29 of 35 patients, PR was found in 3 patients and response was unavailable in the remaining 3 patients due to being lost to follow up or transfer of care. 3/35 pts developed relapse of HL. Of 35 patients, 3 developed BPT (8.6%). All 3 patients were older than age 40 (42-69).ConclusionsIn this retrospective study, pegfilgrastim use with ABVD in HL was associated with a low (2.9%) risk of BPT. This risk was not higher than in our HL ABVD treated pts who did not receive pegfilgrastim (8.6% risk of BPT). All of the pts who developed BPT were >age 40. The 2.9% risk of BPT with pegfilgrastim use contrasts with much higher previously reported BPT with filgrastim use (25.6%)1. One explanation for this may be the delayed onset of pegfilgrastim.1Martin WG et al. J Clin Oncol. 2005; 23 (30): 76142 Janakiram M and O'Brien TE. ASH Proceedings. 2008; 112: Abstract #4950 DisclosuresNo relevant conflicts of interest to declare.

Real-World Safety Experience for Short-Acting Recombinant Human Granulocyte Colony-Stimulating Factor

Introduction: Marketed therapeutic products are subject to periodic benefit-risk evaluation reports (PBRERs), which provide comprehensive worldwide safety assessments and benefit-risk analyses. The short-acting recombinant human granulocyte colony-stimulating factor (rG-CSF) is known as filgrastim (Tevagrastim®, Ratiograstim®, Biograstim®) in Europe (approved in 2008) and tbo-filgrastim (Granix®) in the United States (approved in 2012). In the United States, Granix is indicated for reducing the duration of severe neutropenia in patients with non-myeloid malignancies receiving myelosuppressive anti-cancer drugs associated with a clinically significant incidence of febrile neutropenia. Here, we present the accumulated safety data from the PBRER for the rG-CSFs collected in a 3-year period from the 52 countries in which the product was registered.Methods: Cumulative data were collected since initial approval in 2008. This PBRER period includes data captured from September 16, 2012, to September 15, 2015. Data were collected from spontaneous reports submitted by healthcare professionals and consumers, the scientific literature, competent authorities, and solicited case reports. Adverse reactions were categorized by system organ class (SOC), source, and seriousness. Pharmacovigilance in Europe requires screening of all adverse reaction reports and antibody assessment for cases of suspected immunogenicity. Safety concerns identified by the originator during the use of filgrastim were described in the risk management plan (RMP; version 8; dated 14 May 2012).Results: During this PBRER period, the estimated exposure to the rG-CSFs was ~4,314,994 patient-days. As of September 15, 2015, the estimated cumulative exposure to the rG-CSFs was ~8,741,835 patient-days over 7 years. Estimated cumulative exposure to the rG-CSFs in clinical trials were 190 patient-days in healthy subjects and 22,099 patient-days in patients with cancer. The global safety database processed 561 rG-CSFs case reports from initial product approval through September 15, 2015 (~9 years), including 339 (60%) from this PBRER period (~3 years). Postmarketing data sources cumulatively reported 1133 adverse reactions, 702 (62%) from this PBRER period. The most common adverse events (AEs) reported during this PBRER period per SOC are summarized in the figure. The most frequently reported serious AEs associate with general disorders and administration site conditions during this period were pyrexia (11 reports) and ineffective drug (8). Reports of serious bone pain (3 reports), back pain (2), muscular weakness (2), musculoskeletal pain (2), and myalgia (2) were also received during this period. The most common AEs associated with serious skin conditions were pruritus and urticarial (5 reports each). Two additional safety concerns (capillary leak syndrome [CLS] and cytokine release syndrome [CRS]) were identified by the originator during the use of filgrastim and were subsequently added to the RMP based on recommendations from the Pharmacovigilance Risk Assessment Committee. As of September 15, 2015, one report of CLS and no reports of CRS have been received. Overall, reported cases of immunogenicity showed no impact on efficacy or pharmacokinetics/ pharmacodynamics of the rG-CSFs. Updated data will be presented at the conference as available.Conclusions: No significant changes in the safety or risk-benefit profiles were identified for the rG-CSFs relative to other filgrastim products during this reporting period, and reported cases of immunogenicity showed no clinically relevant impact. [Display omitted] DisclosuresAbboud:Teva: Speakers Bureau; Alexion, Baxalta, Pharmacyclics, Takeda, Cardinal Health: Honoraria; Merck, Teva, Novartis, Pfizer, Seattle Genetics: Research Funding; Gerson and Lehman Group (GLG): Consultancy. Lang:Teva ratiopharm: Employment. Lammerich:Teva ratiopharm/Teva Pharmaceuticals, Inc.: Employment. Buchner:Merckle GmbH member of TEVA Group: Employment; Teva Pharmaceuticals, Inc.: Equity Ownership. Liu:Teva Pharmaceuticals, Inc.: Employment. Mueller:Teva Pharmaceuticals, Inc.: Employment, Equity Ownership. Pathak:Teva Pharmaceuticals: Employment, Equity Ownership.

Recombinant granulocyte colony-stimulating factor (rG-CSF) in the management of neutropenia induced by anthracyclines and ifosfamide in patients with soft tissue sarcomas (NEUSAR).

Anthracycline and ifosfamide-based chemotherapy represents a widely used regimen both in early and advanced settings in soft tissue sarcoma (STS). Prophylaxis with granulocyte colony-stimulating factor (G-CSF) reduces the severity of chemotherapy-induced neutropenia. The aim of this study was to assess the efficacy and safety of biosimilar G-CSF in these patients. Between 2003 and 2013, 67 patients with soft tissue tumors under epirubicin and ifosfamide (EI) treatment receiving biosimilar filgrastim (Zarzio®), originator filgrastim (Granulokine®, Neupogen®), and lenograstim (only originator Myelostim®) as primary prophylaxis for a total of 260cycles of therapy were retrospectively analyzed. Baseline patient characteristics were summarized in a propensity score (PS). The incidence of febrile neutropenia (FN) was 44.0% in biosimilar filgrastim, 40.0% in originator filgrastim, and 45.5% in the lenograstim groups (p=0.935). All grade and G4 neutropenia were similar in the three groups with the same safety profile. The use of biosimilar filgrastim achieved cost savings of €225.25 over originator filgrastim and €262.00 over lenograstim. Biosimilar G-CSF was effective in preventing FN and in reducing the need for hospitalization in STS patients undergoing EI treatment. It also proved comparable to its reference products from both a clinical and cost-effective standpoint.

How did the Introduction of Biosimilar Filgrastim Influence the Prescribing Pattern of Granulocyte Colony-Stimulating Factors? Results from a Multicentre, Population-Based Study, from Five Italian Centres in the Years 2009-2014.

Granulocyte colony-stimulating factors (G-CSFs) are biological products for which the main indication of use is chemotherapy-induced neutropenia. Biosimilars of G-CSFs have been available in Europe since 2007. The objective of this study was to investigate the prescribing pattern of G-CSFs in five Italian centres using different healthcare policy interventions to promote the use of biosimilars in routine care. This retrospective, population-based drug utilization study was conducted during the years 2009-2014 using the administrative databases of the Caserta, Treviso and Palermo Local Health Units (LHUs) and the Tuscany and Umbria regions. G-CSF users were characterized and the prevalence of use, proportion of biosimilar users and switching pattern of different G-CSFs were evaluated over time and across centres. Overall, 30,247 patients were treated with G-CSFs in the years 2009-2014, of which 29,083 (96.2%) were naïve users. The overall prevalence of G-CSF use increased from 0.8 per 1000 inhabitants in 2009 to 1.1 per 1000 in 2014. An increase in the proportion of the use of the biosimilar filgrastim by the total G-CSF users was observed in all centres: from 0.2% (2009) to 66.2% (2014). However, heterogeneity across different centres was reported, with the largest increase in Treviso LHU (from 0 to 89.1% from 2009 to 2014). During the first year of treatment, switching between different G-CSFs was frequent (20.3%). Heterogeneity in the use of G-CSF and, in particular, biosimilar filgrastim across different Italian centres was observed, probably due to different regional healthcare policy interventions. During the first year of treatment, switching between different G-CSFs was frequent. Considering the impact of biological drugs on pharmaceutical expenses, it is necessary to harmonize healthcare policies promoting the use of biological drugs with the lowest cost.

Quality Improvement: Decreasing Length of Stay, TPN and Filgrastim Usage in Autologous Stem Cell Transplant Patients

We used the Plan-Do-Study-Act quality improvement methodology to reduce the length of stay (LOS) for autologous stem cell transplant (ASCT) patients. Baseline data were collected from the electronic medical records of patients admitted for ASCT from January – April 2014 to serve as the control population. Changes in care were implemented during April 2014. The post implementation comparison intervals were phase I from May – October 2014 and phase II from November 2014 – April 2015 after re-education of staff. Changes in workflow included changing filgrastim administration post-stem cell infusion from day +6 to day +9. The utilization of TPN was changed from individual provider preferences to protocol based with a nutritional team member rounding with the inpatient hematology team. Criteria for starting TPN included patients with less than 50% required calories for >7 days, severe mucositis, or weight loss (>10%) from the time of hospital admission. TPN was not used within the first week of hospital admission unless clinically required. Time to neutrophil engraftment and LOS were monitored continuously during the study period. The pre-implementation median LOS was 17 days (n=16, range: 14-22 days) with a median neutrophil engraftment day of +12 (n=22, range: 10-13). Post-implementation with 3 days less of filgrastim, the median neutrophil engraftment day remained +12 (n=45, range: 10-14). Overall there was a decrease in the median LOS to 16 days (n=46, range: 14-29 days). The cost savings was approximately $1500 per patient due to the reduced filgrastim use and administration and approximately $8500 per patient for the decreased LOS. TPN use was 10% (n=20) at baseline. Post-implementation TPN use decreased to 8.33% (n=24) during phase I and 0% (n=23) during phase II. For the patients receiving TPN during phase I the start day went from +7.5 (pre-implementation) to day +11 and the average number of days on TPN decreased from 4.5 to 3 days. The cost savings was approximately $1000 per patient not requiring TPN. The implementation of protocol driven quality improvement parameters decreased our ASCT patients LOS by one day, decreased TPN use to 0% and decreased the need and cost associated with 3 days of filgrastim use. Re-education of providers at the beginning of phase II contributed to this continued improvement. These practice improvements have important clinical implications. Reduced LOS decreases infection risks and improves the quality of life (QOL) for patients and caregivers. Limiting TPN use also reduces the risks of infection and hepatic dysfunction. Decreased use of filgrastim decreases the risk of side effects including injection site reactions and bone pain, further improving patient QOL. Decreased LOS, TPN and filgrastim use, are all economically preferred and beneficial. An ongoing study is evaluating the same parameters in allogenic BMT patients.

A Retrospective Review of Engraftment Data for Tbo-Filgrastim Vs. Filgrastim in Patients Undergoing High Dose Chemotherapy and Autologous Stem Cell Transplantation

Background:Patients undergoing high dose chemotherapy and autologous stem cell transplantation (HDC/SCT) have received Filgrastim from day +1 through neutrophil engraftment as per institutional guidelines. Recombinant Flgrastim (Tbo-Filgrastim) has not been compared with Filgrastim post SCT for kinetics of engraftment after high dose chemotherapy and stem cell transplantation. Tbo-Filgrastim was introduced in April 2014 at our center and is currently used only in the inpatient setting after HDC/SCT; while the use of Filgrastim is exclusive in the outpatient setting after HDC/SCT. Currently Tbo-Filgrastim is not approved as a biosimilar in the US (only indicated for reduction in the duration of severe neutropenia in patients with non-myeloid malignancies) and does not carry an "interchangeability" designation.Objective:To review neutrophil and platelet engraftment data for patients who received Tbo-Filgrastim compared to patients who received Filgrastim after HDC/SCT.Methods:A comprehensive chart review was conducted on 34 patients from Sept 2013 to May 2015: 17 patients received Tbo-Filgrastim and 17 patients received Filgrastim after SCT. All discharge summaries and electronic medical records were reviewed for inpatient and outpatient status and engraftment data. A Wilcoxon rank sum test was conducted to compare the median time to engraftment for patients who received Tbo-Filgrastim vs. Filgrastim due to the non-parametric nature of the data. A Chi-Square test was done to compare proportions of patients that had febrile neutropenia. Subjects who did not receive Tbo-Filgrastim as an inpatient after the institution switch (n=3) were excluded from analyses.Results:Table 1Tbo-Filgrastim (n=17)Filgrastim (n=17)Time period4/2014-5/20159/2013 -3/2014Disease TypeAL Amyloidosis10 (59%)14 (82%)Myeloma6 (35%)2 (12%)Lymphoma1 (6%)1 (6%)Median Age, years (range)57 (41-72)54 (41-68)Male11 (65%)10 (59%)Female6 (35%)7 (41%)Mobilization RegimenG-CSF7 (41%)13 (76%)Chemo + GCSF3 (18%)1 (6%)G-CSF + Plerixafor6 (35%)2 (12%)Preparative RegimenMelphalan @ 200mg/m210 (59%)13 (76%)Melphalan @ 140mg/m26 (35%)3 (18%)CBV1 (6%)1 (6%)Median number of stem cell collection; 106 CD 34+/kg (range)13.9 (1.8- 21.8)9.1 (3.9- 16.6)Median number of stem cells reinfusion; 106 CD 34+/kg (range)8.4 (3.0-17.4)6.9 (3.5-10.5)Febrile Neutropenia10 (59%)8 (47%) p value=0.73Median days to neutrophil engraftment (range)11 (9-14)10 (8-15) p value=0.07Median days to platelet engraftment (range)12 (10-21)12 (9-27) p value=0.49Median days of growth factor, (range)6 (3-10)10 (8-15)Death01Conclusions:In this retrospective chart review, we did not find any significant difference in time to neutrophil engraftment after HDC/SCT when comparing patients who received Filgrastim and then switched to Tbo-Filgrastim after SCT. Even though Tbo-Filgrastim is not approved as a biosimilar and lacks interchangeability designation, based on our experience the safety, efficacy and immunogenicity is comparable to Filgrastim and there are no clinical meaningful differences between the two products. However, this data warrants further prospective research with a larger sample size to confirm these findings. DisclosuresNo relevant conflicts of interest to declare.

Prophylactic Biosimilar Filgrastim Treatment during Cytotoxic Chemotherapy in Patients with Malignant Diseases: The Venice Observational Study

▪Introduction: Among other serious adverse events, febrile neutropenia (FN) is a serious, frequent complication associated with cytotoxic chemotherapy (CT). Biosimilar filgrastim (NivestimTM, Hospira Inc.) is a granulocyte-colony stimulating factor (G-CSF)approved for use in Europe since 2010 for the reduction in the duration of neutropenia and the incidence of FN in patients treated with cytotoxic CT for malignancy. The VENICE study was conducted to observe the tolerability, safety and efficacy of prophylactic treatment using biosimilar filgrastim among in-patients receiving cytotoxic CT for cancer outside the clinical trial setting in the context of real-life, day-to-day medical practice. This study is of particular relevancy due to the propensity for biosimilar G-CSF to lower overall costs of cancer treatment. ClinicalTrials.gov Identifier: NCT01627990Study Design: The study was conducted as a prospective, non-interventional study at 48 sites in Germany. Patients being treated for solid tumors or malignant hematologic tumors except for chronic myeloid leukemia (CML) or myelodysplastic syndrome (MDS) who had provided informed consent and for whom cytotoxic CT and biosimilar filgrastim treatment was planned were enrolled in the study. Data on demographics, clinical characteristics, treatment-related data on efficacy and safety (AEs including FN) and hospitalizations were collected. Three study visits were planned: at recruitment, at end of first biosimilar filgrastim administration and at end of CT or end of study.Results: The study included 386 adult patients undergoing cytotoxic CT who were treated with biosimilar filgrastim prophylactically to reduce the duration of neutropenia and to reduce incidence of chemotherapy-induced FN. Patients were 81% female with a mean age of 60 years. At baseline, 43% of the patients had already received CT and previous FN was reported by only 3% of patients. A total of 338 patients (88%) had solid tumors and 49 (13%) had hematological malignancies. Antibiotic prophylaxis was taken by 13% of patients at inclusion. Only 9% of the patients had received G-CSF from the first cycle. The majority (64%) of patients received biosimilar filgrastim as primary prophylaxis and 36% as secondary prophylaxis.At least one hospitalization was reported by 24 (6%) of 382 patients in the safety analysis set and the median hospital stay for these patients was 10 days. Hospitalization due to FN or infection was reported for 2% of patients.Only 1% of patients had a delay in their CT due to FN after the first biosimilar filgrastim treatment and for only 5% of patients, the CT in any subsequent CT cycle was delayed due to neutropenia. Reduction of CT dose after first biosimilar filgrastim treatment due to FN was reported for only 1% of patients and reduction of CT dose in any subsequent cycle due to neutropenia was reported for only 5% of patients.The median duration between the last dose of CT and treatment with biosimilar filgrastim was 5 days. The majority of patients were prescribed the 30 million units (MU) dose of biosimilar filgrastim administered SC. The median duration of treatment was 4 days. Most patients administered the biosimilar filgrastim injection themselves at both treatment visits (78% at first visit and 69% at last visit). Most of the self-applicators reported that the application was easy or very easy.During the study, 24% of patients experienced ≥1 AE that was at least possibly related to biosimilar filgrastim treatment. The treatment related AEs reported most frequently were musculoskeletal and connective tissue disorders (11%); general disorders and administration site conditions (5%); and blood and lymphatic system disorders (5%).Conclusions: The VENICE non-interventional study aimed to evaluate the use of biosimilar filgrastim according to the label approved usage of the biosimilar filgrastim in order to collect additional real world data on the tolerability, safety and efficacy in cancer patients. Biosimilar filgrastim was effective and well-tolerated in both the primary and secondary prophylactic settings in patients undergoing chemotherapy for solid tumors and hematological malignancies. DisclosuresErdlenbruch:Hospira Germany: Employment.

Use of biosimilar filgrastim yields substantial cost savings

Use of biosimilar filgrastim yields substantial cost savings

Biosimilar Compared with Originator Filgrastim for Autologous Stems CELL Mobilisation: A Prospective-Historical Control Study in Multiple Myeloma REAL-Life Setting

Introduction:Biosimilars of filgrastim have been available since 2008 and are now in widespread use also for stem cells (SCs) mobilization. There are no previously published data on the use of biosimilar G-CSF for peripheral blood (PB) SCs collection only in patients with Multiple Myeloma (MM) as they always had been presented aggregated with other different hematological malignancies. Here we report the use of a biosimilar filgrastim (Zarzio®) compared with a matched historical control group in PBSCs in patients with de-novo MM treated with reference product (Neupogen®) and scheduled to receive a double autologous transplantation.Material and Methods: A total of 26 consecutive patients received biosimilar filgrastim after cyclophosphamide (CTX) 4g/m2 chemotherapy for PBSCs mobilization between January and July 2014, this group was compared with a matched historical control cohort (n=26) who had been treated with originator filgrastim between 2012 and 2013. In both groups G-CSF was administered 5 μg/kg/day until almost a minimal count of 4 x106 CD34+ cells/kg was collect. Monitoring of peripheral blood CD34+ cell concentrations began as soon as WBC recovery reached 1x109/L and leukapheresis was initiated when the CD34+cell concentration reached 10/mL.Results: Characteristics (age, gender, body weight, type of induction CHT, radiation therapy) were similar in both groups. The median peak CD34+ cells value was 187.8 ± 159.5 x ml in the biosimilar group compared with 223.7 ± 206.5 x ml in the originator group (P=n.s.). The median number of leukapheresis necessary to harvest a minimal count of 4 and 8 x10E6 CD34+/kg was similar in both biosimilar and originator groups: 1.4 ± 0.6 vs 1.3 ± 0.6 (P=n.s.) and 1.8 ± 0.8 vs 1.4 ± 0.7 (P=n.s), respectively. One and 3 patients failed to mobilize 4 and 8 x 10 E /kg CD34+ cells in the biosimilar group compared with 3 and 8 patients in the originator group (P=n.s), respectively). Short-term hematological reconstitution was evaluated for all transplanted patients. Number of CD34+ cells reinfused at the first transplant were 4.8 ± 0.75x10E6/Kg in the biosimilar group compared with 5.1 ± 0.75x10E6/Kg in the originator group (P=n.s.). Median time to neutrophil engraftment (>500/μl) was similar in both the biosimilar and originator groups (10.7 ± 0.8 vs 10.3 ± 1.1 days; P=n.s), as was platelet recovery (13.6 ± 1.8 vs13.4 ± 1.2 days; P=n.s.Conclusions:Our study shows that biosimilar filgrastim administered following chemotherapy is equivalent to originator filgrastim for autologous stem cell mobilization and PBSCs collection when used with the same schedules and doses in a MM real life setting. Long-term follow-up is required to confirm the safety of biosimilar and originator G-CSF. DisclosuresNo relevant conflicts of interest to declare.

Filgrastim use in the emergency department of a Spanish general hospital.

Febrile neutropenia is a cause of dose reduction in hematological cancer treatments, with patient risk of infection proportional to duration and severity. In addition, colony-stimulating factors have been shown to be beneficial in a patient subgroup, although they are probably overused in the clinical setting. Evaluation of compliance with American Society of Clinical Oncology 2006 criteria when it comes to filgrastim use in the Emergency Department of a Spanish general hospital. A prospective observational study from August 2011 to February 2012 in a tertiary Spanish General Hospital. We included all patients prescribed with filgrastim in the Emergency Department. Data was collected on demographics, the pharmacotherapy history, the administered chemoprophylaxis, and the destination after discharge from a clinical department, the complete blood count, and the presence of fever >= 38 °C. 51 patients were recorded over the period of the study. 27.45% of prescriptions complied with the clinical practice guideline criteria given the risk of febrile neutropenia, whereas 72.34% of prescriptions did not comply with the criteria, 17.65% of which did not fulfil any requirements. A high percentage of colony-stimulating factors use in the Emergency Department does not comply with the medical practice guideline.

PCN106 - Cost-Effectiveness of Prophylactic Use of Filgrastim in Adults with Acute Leukemia Lymphoblastic Colombia

PCN106 - Cost-Effectiveness of Prophylactic Use of Filgrastim in Adults with Acute Leukemia Lymphoblastic Colombia

White blood cell growth factor use in an outpatient oncology clinic: Lessons and opportunities learned

The increased use and high cost associated with white blood cell growth factors at our outpatient oncology clinic has prompted this evaluation. The objectives of this study were to categorize the indication for use of pegfilgrastim and filgrastim; evaluate the administration of these white blood cell growth factors; identify opportunities for cost savings; and identify ways to increase prescriber adherence to evidence-based practice guidelines. This medication use evaluation study involved retrospective data collection from patient medical records. Adult oncology patients treated in the outpatient oncology clinic who received filgrastim or pegfilgrastim were identified and included in this study. Computerized patient records were used to collect data on patient demographics, risk factors for febrile neutropenia, prescribing patterns for filgrastim and pegfilgrastim, and chemotherapy regimens. The number of pegfilgrastim and filgrastim doses were predominately used for primary prophylaxis following chemotherapy treatment. Of the 234 total doses of pegfilgrastim used in the setting of primary prophylaxis, 28 (12%), 134 (57%), and 72 (31%) doses were given to patients receiving chemotherapy regimens associated with a high risk (>20%), intermediate risk (10-20%), and low risk (<10%) of febrile neutropenia, respectively. The total number of pegfilgrastim doses used in secondary prophylaxis was 78; 20 (26%) and 58 (74%) of these doses were given to patients receiving chemotherapy regimens associated with an intermediate risk and low risk of febrile neutropenia, respectively. This study revealed a significant portion of prescribed growth factor use that was not in accordance with clinical practice guidelines.