Administration Of Pegfilgrastim Research Articles

Quantification of the Cellular Content of Platelet Rich Plasma Harvested After Injection of Filgrastim Versus Pegfilgrastim Biosimilars: A Prospective, Single Center, Crossover Study

BackgroundHematopoietic stem cells (HSCs) are primitive cells that often appear in peripheral blood (PB) following mobilization events from bone marrow due to stress, injury, exercise, or pharmaceutical agents like filgrastim and pegfilgrastim. These cells can be concentrated into platelet-rich plasma (PRP), widely used in orthopedics. Filgrastim requires consecutive daily doses, while pegfilgrastim requires a single dose. Hypothesis/PurposeThis crossover study aimed to compare the safety profiles of filgrastim and pegfilgrastim administration and quantify the cellular content of PRP derived from peripheral blood following drug administration. We hypothesized comparable rates and severity of adverse events among participants, along with similar cellular content in the PRP products. Study DesignProspective, single center, cross over and controlled laboratory study MethodsHealthy participants aged 19-39 years and weighing 50-100 kilograms were screened and enrolled. They underwent a crossover design with two interventions separated by a washout period: four days of 10mcg/kg filgrastim or a single 6mcg/kg pegfilgrastim injection. Peripheral blood samples were collected before and after each intervention to produce PRP samples for cellular comparison in vitro. Adverse events (AEs) were monitored for severity and frequency throughout the study. Results10 healthy male participants were included in this study. The mean ± (SD) age of the participants was 28.30 ± 6.48 years, with a mean ± (SD) BMI of 25.29 ± 3.80. The most common adverse events for filgrastim included fatigue (36%) myalgia (36%) and back pain (9.1%), and the most common adverse events for pegfilgrastim included myalgia (31%), fatigue (23%), and back pain (23%). There were no significant differences in safety data between filgrastim and pegfilgrastim in terms of adverse event occurrence (P=0.49) nor relationship to study drug (P>0.99). The baseline PRP samples had an average TNC count of mean ± (SD) 3,844.77 ± 1,326.71, the filgrastim PRP samples had 6,939.20 ± 6,252.24, and the pegfilgrastim PRP samples had 8,923.20 ± 3,258.09. The baseline PRP samples had an average TNC concentration of mean ± (SD) 1.33×107±4.60×106 cells/mL, the filgrastim PRP samples had 1.83×107±1.81×107 cells/mL, and the pegfilgrastim samples had 3.09×107±1.13×107cells/mL. Significant differences were found in both TNC count (P=0.010) and TNC concentration (P=0.004). Specifically, there were significantly higher average TNC counts in the pegfilgrastim PRP samples compared to control (P=0.0082), but there were no differences between the filgrastim and pegfilgrastim PRP samples (P=0.1515). There was also a significantly higher average TNC concentration in the pegfilgrastim PRP samples compared to control PRP (P=0.0082) and compared to filgrastim PRP (P=0.0197). White blood cells, basophils, and immature granulocytes were significantly higher in the pegfilgrastim PRP compared to control (P=0.0082, P=0.0002, and P=0.0272). Neutrophils were significantly higher in both the filgrastim PRP (P=0.0357) and pegfilgrastim PRP (P=0.0024) compared to control. There were no differences detected for these measures among the filgrastim and pegfilgrastim PRP groups. None of the cultured PRP samples produced CFU-Fs, however cellular growth was qualitatively observed after overnight incubation. All PRP products expressed high levels (>88%) of HPC/HSC-specific CD45+, CD34+, CD45dim+, and HPC/HSC+ markers. There were no statistically significant differences in cell-surface antigens between the PRP products. ConclusionsThis prospective, single center, cross over and controlled laboratory study demonstrated that filgrastim and pegfilgrastim administration appears safe and pegfilgrastim is equivalent to filgrastim for the mobilization of white blood cells and cells expressing hematopoietic cell-surface markers into the peripheral blood and consequently, into the derived platelet rich plasma product. Clinical RelevanceThis study presents pegfilgrastim as a single-injection alternative to filgrastim for the mobilization of HSCs into the PB and subsequent PB-derived PRP, which is more convenient and less invasive for patients.

A retrospective study on the efficacy of pegfilgrastim-filgrastim combination regimen in the mobilization for autologous stem cell transplantation in lymphoma patients

BACKGROUNDThe high mobilization failure rate with the mobilization strategy of combining chemotherapy and filgrastim (rhG-CSF) in autologous hematopoietic stem cell transplantation (auto-HSCT) in lymphomas is one of the unresolved issues. Whether the combination of polyethylene glycol filgrastim [pegfilgrastim (PEG-FIL), PEG-rhG-CSF] and filgrastim (FIL) improves the mobilization success rate and the timing of combination therapy has not been studied. METHODS107 lymphoma patients who received auto-HSCT were retrospectively enrolled and divided into groups of PEG+FIL and FIL. The group of PEG+FIL received pegfilgrastim (9 mg) on the third day of the chemotherapy, followed by filgrastim (10 μg/kg/day) based on the counts of peripheral blood stem cells (PBSC). The group of FIL received filgrastim 10 μg /kg/day depending on the number of PBSCs. RESULTSThe incidence of neutropenic fever in the group of PEG+FIL was significantly lower than in the group of FIL. The mean recovery time of leukocytes at autologous stem cell transplantation was significantly shorter in the group of PEG+FIL than in the group of FIL. Compared to the groups of FIL, the group of PEG+FIL had lower hospitalization costs. We found that the combination therapy is more recommended for patients with a bone marrow hematopoietic area of less than 30%. Filgrastim is best administered 5-6 days after pegfilgrastim administration. CONCLUSIONSCompared to conventional filgrastim mobilization, the combination of pegfilgrastim and filgrastim schedule has high efficacy, non-inferior safety, and superior health economic benefits during auto-HSCT.

Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients.

To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival. Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72h) or delayed administration (after 72h) of HiDAC. The difference in neutrophil recovery time was similar between the early and delayed groups (18days versus 19days, p < 0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p = 0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p = 0.28) as well as a trend towards longer median survival (16months versus 19months, p = 0.69) and overall survival (21months versus 31months, p = 0.47). A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed administration of pegfilgrastim in these patients.

Prophylactic pegfilgrastim reduces febrile neutropenia in ramucirumab plus docetaxel after chemoimmunotherapy in advanced NSCLC: post hoc analysis from NEJ051

Ramucirumab plus docetaxel (RD) can cause febrile neutropenia (FN), which frequently requires the prophylactic administration of pegfilgrastim. However, the effects of prophylactic pegfilgrastim on FN prevention, therapeutic efficacy, and prognosis after RD have not been fully evaluated in patients with advanced non-small-cell lung cancer (NSCLC). Two hundred and eighty-eight patients with advanced NSCLC who received RD as second-line therapy after platinum-based chemotherapy plus PD-1 blockade were included. Patients were divided into groups with and without prophylactic pegfilgrastim, and adverse events, efficacy, and prognosis were compared between both groups. Of the 288 patients, 247 received prophylactic pegfilgrastim and 41 did not. The frequency of grade 3/4 neutropenia was 62 patients (25.1%) in the pegfilgrastim group and 28 (68.3%) in the control group (p < 0.001). The frequency of FN was 25 patients (10.1%) in the pegfilgrastim group and 10 (24.4%) in the control group (p = 0.018). The objective response rate was 31.2% and 14.6% in the pegfilgrastim and control groups (p = 0.039), respectively. The disease control rate was 72.9% in the pegfilgrastim group and 51.2% in the control group (p = 0.009). Median progression free survival was 4.3 months in the pegfilgrastim group and 2.5 months in the control group (p = 0.002). The median overall survival was 12.8 and 8.1 months in the pegfilgrastim and control groups (p = 0.004), respectively. Prophylactic pegfilgrastim for RD reduced the frequency of grade 3/4 neutropenia and febrile neutropenia and did not appear to be detrimental to patient outcome RD.Clinical Trial Registration Number: UMIN000042333.

Docetaxel, cisplatin, and fluorouracil with pegfilgrastim on day 3 as neoadjuvant chemotherapy for esophageal cancer.

A high risk of febrile neutropenia (FN) from neoadjuvant chemotherapy with docetaxel, cisplatin, and fluorouracil (DCF) for esophageal cancer has been reported. The optimal timing of prophylactic use of pegfilgrastim remains to be elucidated. To evaluate the effect of pegfilgrastim administered on day 3, we conducted a feasibility study. Chemotherapy consisted of intravenous administration of docetaxel (70 mg/m2 per day) and cisplatin (70 mg/m2 per day) on day 1 and continuous infusion of 5-fluorouracil (750 mg/m2 per day) on days 1-5. Pegfilgrastim was given as a single subcutaneous injection at a dose of 3.6 mg on day 3 during each treatment course. This regimen was repeated every 3 weeks for up to a maximum of three courses. Prophylactic antibiotics were not needed but were allowed to be given at the discretion of the physician. The primary endpoint was the incidence of FN. Twenty-six patients were administered DCF in combination with pegfilgrastim on day 3. After the first course of DCF, 10 out of 26 patients (38.5%) experienced grade 4 neutropenia, and two patients (7.7%) experienced FN. Of the 14 patients who did not receive prophylactic antibiotics, four had grade 4 neutropenia, including two who developed FN. On the contrary, of the 12 patients who received prophylactic levofloxacin, six had grade 4 neutropenia, but no cases of FN were observed. Administration of pegfilgrastim on day 3 was not sufficient to prevent FN due to DCF treatment, and prophylactic administration of both pegfilgrastim and antibiotics could be a solution.

Pegfilgrastim for the management of neutropenia during neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil in esophageal cancer patients.

Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.

The Combination of Pegfilgrastim and Filgrastim Improves the Outcomes of Mobilization and Engraftment after Transplantation of Autologous Hematopoietic Stem Cells for the Treatment of Lymphoma

BACKGROUND : Hematopoietic stem cell transplantation (HSCT) is broadly utilized for the treatment of lymphoma. Autologous peripheral blood stem cell (PBSC) transplantation (ASCT) requires mobilization of hematopoietic stem cell/ hematopoietic progenitor cell (HSC/HPC) in peripheral blood (PB) to collect HSCs. The high mobilization failure rate with the mobilization strategy of combining chemotherapy and filgrastim (rhG-CSF, recombinant human granulocyte colony-stimulating factor) in ASCT is one of the unresolved issues. Whether the combination of polyethylene glycol filgrastim [pegfilgrastim (PEG-FIL), PEG-rhG-CSF] and filgrastim (FIL) improves the mobilization success rate and the timing of combination therapy has not been studied. METHODS: To test the hypothesis that the combination of pegfilgrastim and filgrastim schedule has superiority, we retrospectively investigated a cohort of 107 lymphoma patients who received auto-HSCT and collection in the First Hospital of Jilin University from Jan 1st 2015 to Dec 1st 2022. These patients were categorized into PEG+FIL group and FIL group. The group of PEG+FIL received pegfilgrastim (9 mg) on the third day of the chemotherapy, followed by filgrastim (10 μg/kg/day) based on the counts of peripheral blood stem cells (PBSC). The group of FIL received filgrastim 10 μg /kg/day depending on the number PBSCs. Demographic information, laboratory results, and treatment plans were collected for these two groups of patients. RESULTS：We compared their mobilization efficacy (mononuclear cell [MNC] and CD34 + cell counts) and transplantation efficacy (days to leukocyte and platelet recovery post-transplantation). Successful ASCT mobilization was achieved in 93 patients (86.9%), with the PEG+FIL group exhibiting a higher success rate compared to the FIL group (89.2% [58/65] vs. 83.3% [35/42], p = 0.032). The PEG+FIL group also demonstrated significantly higher CD34+ cell counts [MNC: 8.9 (6.9, 11.2) vs. 7.8 (6.2, 9.8) × 10 8 cells/kg, p = 0.024; CD34 + cell count: 7.5 (5.6, 13.0) vs. 4.9 (3.2, 9.2) × 10 6 cells/kg, p = 0.008] and a lower incidence of neutropenic fever compared to the FIL group (11.8% vs. 24.3%, p = 0.038). The PEG+FIL group also demonstrated a shorter mean leukocyte recovery time in autologous stem cell transplantation than the FIL group (10.02 ± 0.73 vs. 10.9 ± 1.1 days, p &amp;lt; 0.001). To delve deeper into the safety considerations of both groups, we evaluated the advantages of each regimen and the methodologies for selecting time windows. A bone marrow aspiration and biopsy were performed on all patients before stem cell collection. Among 18 patients who had a hematopoietic area less than 30% and a fat area greater than 40%, 10 were in the PEG+FIL group and 8 in the FIL group. For patients who required only one collection, the durability was 80% in the PEG+FIL group compared to 0% in the FIL group (p &amp;lt; 0.01), indicating a superior recommendation for patients with a bone marrow hematopoietic area of less than 30%. In the PEG+FIL group, monitoring was carried out for PB CD34 + percentage and WBC count following pegfilgrastim administration, with subsequent computation of CD34 + cells in PB. Filgrastim administration was found to be optimal 5-6 days post-pegfilgrastim administration. CONCLUSIONS: In conclusion, relative to conventional filgrastim mobilization, the conjunctive use of pegfilgrastim and filgrastim demonstrates superior efficacy, non-inferior safety during ASCT. The schedule enhanced the the outcomes of mobilization in the patients of less hematopoietic area. KEY WORDS: Pegylated recombinant human granulocyte-stimulating factor (pegfilgrastim, PEG-rhG-CSF), recombinant human granulocyte-colony stimulating factor (filgrastim, rhG-CSF), lymphoma, hematopoietic stem cell transplantation (HSCT) autologous hematopoietic stem cell mobilization.

Efficacy and safety of second-line therapy of docetaxel plus ramucirumab after first-line platinum-based chemotherapy plus immune checkpoint inhibitors in non-small cell lung cancer (SCORPION): a multicenter, open-label, single-arm, phase 2 trial

Immune checkpoint inhibitors (ICI) plus platinum-based chemotherapy has been recognized as a standard first-line therapy in non-small cell lung cancer (NSCLC); however, no prospective clinical trials of docetaxel (DTX) plus ramucirumab (RAM) following first-line ICI plus platinum-based chemotherapy has been reported. In this multicentre, open-label, single-arm, phase 2 trial, we enrolled patients with NSCLC from eight centres in Japan. Patients with metastatic NSCLC with disease progression after platinum-based chemotherapy plus ICI were eligible for the study. Patients were intravenously treated with 60mg/m2 of DTX and 10mg/kg of RAM on day 1 with a strong recommendation of pegfilgrastim administration on day 2 every 3 weeks. The primary end point was objective response rate (ORR) in efficacy analysis population. Safety was assessed in all patients treated at least one dose. The ORR of the null and alternative hypotheses were 10% and 30%, with α error of 0.1 and β error of 0.1. This trial is registered with the Japan Registry for Clinical Trials, jCRTs041190077. Between 16 January, 2020, and 24 August, 2021, 33 patients (median age 66 [range 42-79] years) were enrolled. Thirteen patients (41%) had Eastern Cooperative Oncology Group performance status of 1. Twenty-five patients (78%) had an interval of <60 days after the last administration of ICI. In the efficacy analysis population (n=32), the primary endpoint was met as 11 patients achieved partial response (PR), with ORR of 34.4% (80% CI, 23.1-47.2). Grade ≥3 anaemia and febrile neutropenia were observed in 2 (6%) and 3 (9%) patients, respectively. No treatment-related deaths and no new safety signals were observed. DTX plus RAM demonstrated encouraging antitumor activity with a manageable safety profile in patients who have progressed on front-line ICIs plus platinum-based chemotherapy. The results of this trial can be a helpful reference in conducting further phase III trials of new second-line treatment options. Eli Lilly Japan K.K.

P33-7 Two patients with DLBCL who developed aortitis following pegfilgrastim administration during chemoimmunotherapy

P33-7 Two patients with DLBCL who developed aortitis following pegfilgrastim administration during chemoimmunotherapy

MO40-5 Early administration of pegfilgrastim contributes to the safety of DCF therapy as neoadjuvant chemotherapy for esophageal cancer

MO40-5 Early administration of pegfilgrastim contributes to the safety of DCF therapy as neoadjuvant chemotherapy for esophageal cancer

Aortitis after administration of pegfilgrastim to a healthy donor for peripheral blood stem cell collection

A 45-year-old man who was a sibling donor for allogeneic peripheral blood stem cell transplantation (allo-PBSCT) was administered 7.2 mg of pegfilgrastim for stem cell collection. Peripheral blood stem cells were collected 4 days after administration of pegfilgrastim (Day 4) and 4.32 × 106 /kg of CD34-positive cells per recipient body weight were obtained. Fever of 38 ℃ or higher and left submandibular pain appeared on Day 6. Ultrasonography and contrast-enhanced computed tomography (CT) showed wall thickening of the carotid artery and the abdominal aorta. We carefully excluded the possibilities of cardiovascular and autoimmune diseases by thorough examination, and ultimately diagnosed pegfilgrastim-induced aortitis. The patient’s fever resolved rapidly after treatment with prednisolone (PSL) 1 mg/kg. We began to taper PSL after eight days. Sixty-one days after starting PSL, we confirmed that abdominal aortic wall thickening had improved by contrast-enhanced CT. We continued to taper off PSL and stopped 141 days later with no relapse thereafter. This is the first case report of pegfilgrastim-induced aortitis in an allo-PBSCT donor. Careful monitoring is warranted when administering pegfilgrastim to donors even without past medical history.

Safety of same day administration of pegfilgrastim in breast cancer patients.

e18850 Background: Myelosuppressive therapy plays a crucial role in the treatment plan of patients with cancer; one common toxicity associated with myelosuppressive regimens is neutropenic fever. Pegfilgrastim is approved for use no sooner than 24 hours after receiving cytotoxic therapy, based on the initial FDA indication, requiring a return to clinic or the use of a patented on-body injector placed at the time of treatment. However, alternative schedules assessing earlier administration were never examined in the FDA registration studies. Small studies have suggested that same-day administration of pegfilgrastim can be carried out safely, including a prior safety study at UAB. The present analysis sought to test the non-inferiority of same day pegfilgrastim compared to administration 24-72 hours after cytotoxic chemotherapy. Methods: We undertook a retrospective analysis of 241 breast cancer patients receiving cytotoxic therapy from May 2016 through October 2018. The patient population was predominately Caucasian women with 28% African American or Asian women, and a median age of 55 (33-81). I2B2 codes identified patients with breast cancer receiving adjuvant or neoadjuvant therapy patients receiving same day versus next day pegfilgrastim were compared. Blood counts, delays in therapy, and neutropenic hospitalizations were analyzed for same day versus 24-hour delayed pegfilgrastim at two separate institutions. Dose reduced metastatic regimens were excluded from this review. Results: We comparedthe rate of neutropenia resulting in dose-delay for breast cancer patients receiving standard chemotherapy with administration of pegfilgrastim on both schedules. Overall, neutropenia with fever resulting in delay of subsequent chemotherapy was similar in both groups with same day administration being non-inferior to the standard administration schedule. Other treatment delays due to non-neutropenic conditions included mucositis, port malfunction, COPD, fatigue, and transportation delays. Conclusions: Policies requiring 24-hour delays following chemotherapy for pegfilgrastrim administration, reduce utilization of biosimilars and make the on-body injector, Onpro, a more convenient, albeit expensive option, for patients and the health system. These data suggest that same day administration of pegfilgastrim are non-inferior to delayed administration and may provide both substantial cost savings and quality of life benefits to patients and health care systems by increasing utilization of biosimilars and removing the need for a return visit after chemotherapy. In addition, same day administration also reduces the risk of complications associated with on body injector use, where failure rates of up to 10% are reported.

Artifactual hypoglycaemia may be common in patients with soft tissue sarcoma who received pegfilgrastim-supported chemotherapy

BackgroundRecently, we identified artifactual hypoglycemia in patients with soft tissue sarcoma (STS) who received pegfilgrastim-supported chemotherapy. In the present study, we measured white blood cell count and fasting blood glucose levels after the administration of pegfilgrastim in patients with STS and showed the relationship between artifactual hypoglycemia and white blood cell count. PatientsA total of 19 patients were included in this study. The mean age of the patients was 54 years. They received chemotherapy and administration of pegfilgrastim. Pegfilgrastim was injected subcutaneously 48 h after chemotherapy. No patient had a history of diabetes mellitus. ResultsFifty-nine cycles were administered to 19 patients. One hundred and twenty-eight samples were obtained within one week after the of pegfilgrastim administration. Hypoglycemia was observed in 38 of the 13 patients. There were no symptoms of hypoglycemia in any patient. The white blood cell count in samples from patients with hypoglycemia was significantly higher than that in samples without hypoglycemia (p < 0.001). The median white blood cell count in samples with hypoglycemia was 29,415 and 3420 in samples without hypoglycemia. Age, sex, body mass index, performance status, and red blood cell count were not associated with hypoglycemia. White blood cell count was strongly negatively correlated with fasting blood glucose levels (Pearson's r: 0.786, 95% confidence interval: 0.844–0.709, p < 0.001). Of the 38 samples with hypoglycemia, 32 were measured within 2 days after pegfilgrastim administration. ConclusionIf a lack of symptoms due to hypoglycemia and leukocytes is confirmed, physicians should wait and identify the normalization of the level of glucose according to the neutrophil nadir following temporal leukocytes, which prevents further invasive examination for hypoglycemia.

Factors associated with thrombocytopenia in patients treated with pegfilgrastim.

Pegfilgrastim is a long-acting, granulocyte colony-stimulating factor approved in Japan for the prevention of neutropenia caused by antineoplastic agents. Severe thrombocytopenia was reported with pegfilgrastim, however, the factors associated with thrombocytopenia are unclear. This study aimed to explore the factors associated with thrombocytopenia in patients with metastatic castration-resistant prostate cancer treated with pegfilgrastim for primary prophylaxis of febrile neutropenia (FN) with cabazitaxel. This study included metastatic castration-resistant prostate cancer patients who received pegfilgrastim for primary prophylaxis of FN with cabazitaxel. The timing and severity of thrombocytopenia and factors associated with the reduction rate of platelets were examined in patients who received pegfilgrastim for the primary prevention of FN during the first course of cabazitaxel and by multiple regression analysis. Thrombocytopenia was most common within 7 days of pegfilgrastim administration, with 32 cases of grade 1 and 6 cases of grade 2 as per the Common Terminology Criteria for Adverse Events version 5.0. Multiple regression analysis revealed that the reduction rate of platelets after pegfilgrastim administration was significantly positively correlated with monocytes. In contrast, the presence of liver metastases and neutrophils was significantly negatively correlated with the reduction rate of platelets. Thrombocytopenia due to pegfilgrastim administered as primary prophylaxis for FN with cabazitaxel was most likely to occur within one week after pegfilgrastim administration, suggesting that monocytes, neutrophils, and liver metastases were associated with a reduction in platelets.

Health professionals’ preferences with the use of pegfilgrastim on-body injector at oncology centers in 8 cities in Colombia

BackgroundFebrile neutropenia associated with some chemotherapy regimens can lead to potentially fatal complications and high health care costs. Administration of pegfilgrastim using an On-Body Injector (OBI) may be more convenient for cancer patients and physicians in countries with limited access to high-complexity healthcare. This study aims to describe physician and nurse preferences regarding different options for administration of pegfilgrastim at cancer centers, the chemotherapy schemes for which pegfilgrastim is most frequently prescribed and how healthcare providers prioritize certain administration schemes according to patients’ access to healthcare services.MethodsObservational, descriptive, cross-sectional study and survey, conducted between 2019 and 2020, to describe physician and nurse preferences regarding options for administration of pegfilgrastim at cancer centers, the demographics of the study population and characteristics of participating cancer centers. It included 60 healthcare professionals practicing at oncology centers from 8 cities in Colombia who were contacted and surveyed via telephone. Quantitative continuous variables were summarized using central tendency and dispersion measures.ResultsIt was found that 35% of participants are haemato-oncologists, oncologists or hematologists, 30% are general practitioners, and 35% are other healthcare professionals (i.e., nurse, oncology nurse and head nurse). Our study shows that 48% of physicians prefer the use of OBI, particularly in the scheme of 24 h after myelosuppressive chemotherapy administrations. Regardless of patient frailty and travel time to the clinic, over 90% of healthcare providers (HCPs) prefer to prioritize preventing the patient from having to return to the clinic for pegfilgrastim administration as well as to increase healthcare staff availability through the use of OBI.ConclusionsThe present study is the first one in Colombia that sought the reasons behind HCPs’ choice to use OBI pegfilgrastim. Our results indicate that most professionals prefer to avoid the patient having to re-enter the care center for pegfilgrastim administration to facilitate access to healthcare for patients; patient characteristics and ease of transport are determining factors for respondents when choosing an option for drug administration. We found OBI is the preferred alternative by most HCPs and a good resource optimization strategy in the context of cancer patients’ health care in Colombia.

Higher incidence of pegfilgrastim-induced bone pain in younger patients receiving myelosuppressive chemotherapy: a real-world experience

BackgroundPegfilgrastim is widely used for the prevention of febrile neutropenia (FN) in patients receiving myelosuppressive chemotherapy for various types of cancer. However, pegfilgrastim-induced bone pain (PIBP) is a relevant adverse event occurring during cancer treatment. Thus, we aimed to determine the risk factors for PIBP in real-world clinical practice.Main bodyWe retrospectively collected the clinical records of patients who received pegfilgrastim to support myelosuppressive chemotherapy with at least a 10% risk of FN between 2015 and 2018 at our center. Patients received pegfilgrastim 3.6 mg between days 2 and 7 after chemotherapy administration (day 1) for primary or secondary prophylaxis against FN. All adverse events were recorded according to the Common Terminology Criteria for Adverse Events. Patients who experienced intermittent bone pain in the back, femur, or other anatomic sites after the pegfilgrastim administration were considered to have PIBP. To evaluate the relationship between PIBP incidence and patient characteristics, we performed univariate and multivariate logistic regression analyses to calculate the odds ratios (ORs) of possible risk factors for PIBP. We analyzed the data of 305 patients (median age: 63 years), who underwent 1220 chemotherapy cycles with pegfilgrastim per cycle. Univariate analysis revealed that female sex (vs. male sex), younger age (< 55 years vs. ≥ 55 years), and solid cancers (vs. hematologic cancers) had significantly higher ORs (p < 0.05). However, only younger age (< 55 years) was an independent risk factor for PIBP on multivariate analysis (OR 3.62, 95% confidence interval 1.51–8.69, p = 0.004).ConclusionsYounger age (< 55 years) was significantly associated with a higher risk of PIBP among patients receiving chemotherapy with a ≥ 10% risk of FN. Therefore, oncologists should meticulously formulate management plan for PIBP in younger patients after administering pegfilgrastim.

Efficacy of same-day versus next-day administration of pegfilgrastim for the prevention of chemotherapy-induced febrile neutropenia in breast cancer patients receiving dose-dense doxorubicin and cyclophosphamide: A retrospective multi-site analysis.

Administering pegfilgrastim on the same day as chemotherapy can improve patient satisfaction through convenience and may increase the utilization of cost-effective biosimilars compared to next-day administration, but the effect on clinical outcomes with commonly used breast cancer regimens is unclear. This multi-site, retrospective cohort study included breast cancer patients age 18 years or older who received dose-dense doxorubicin and cyclophosphamide (ddAC) and pegfilgrastim between 1 June 2016 and 31 May 2020. Pegfilgrastim was given on the same day as chemotherapy at one site and the day after chemotherapy at the other two sites. The primary endpoint compared the incidence of febrile neutropenia associated with pegfilgrastim administration timing. A total of 360 patients were reviewed (146 same-day administration and 214 next-day administration). In the same-day group 36 patients (24.6%) developed FN compared to 25 patients (11.7%) in the next-day group (p = 0.002). Same-day administration also significantly increased the incidences of additional acute care visits (11.6% vs 2.8%, p = 0.0016), grade ≥ 3 neutropenia (38.4% vs 13.6%, p < 0.0001), chemotherapy dose reductions (21.2% vs 6.1%, p < 0.0001), and antibiotic use (26.7% vs 12.6%, p = 0.001). Same-day administration did not significantly increase the rate of hospitalization (15% vs 11.2%, p = 0.36) and delay of next chemotherapy cycle by ≥1 day (8.2% vs 6.1%, p = 0.57) due to neutropenic complications. Administering pegfilgrastim on the same day as ddAC led to a significant increase in neutropenic complications. This study confirms the need to administer pegfilgrastim the day after chemotherapy in breast cancer patients receiving ddAC.

Predictive Factors of Febrile Neutropenia After Primary Prophylactic Pegfilgrastim With DCF Chemotherapy for Esophageal Cancer.

We investigated the predictive factors of febrile neutropenia (FN) after the administration of pegfilgrastim as primary prophylaxis in patients with esophageal cancer who received neoadjuvant chemotherapy with docetaxel, cisplatin, and 5-fluorouracil (DCF) to support the appropriate management of FN. We evaluated changes in neutrophil counts and relative dose intensity (RDI) after the incidence of FN. This retrospective study involved 122 patients with esophageal cancer who were treated with DCF and pegfilgrastim at Showa University Hospital, Japan, between April 2016 and August 2021. The primary outcome was FN incidence after cycle 1 of DCF chemotherapy. The significant independent factors associated with FN incidence were selected using the multivariate analysis. Changes in neutrophil counts and RDI were compared between the FN and non-FN groups. One-hundred patients were included in the analysis. The incidence of FN in cycle 1 was 21%. In the multivariate analysis, geriatric nutritional risk index (GNRI) <92 [odds ratio (OR)=13.162, p<0.001] and combination of platelet and neutrophil-to-lymphocyte ratio (COP-NLR) score of 0 (OR=4.619, p=0.012) were independent predictors of FN. The neutrophil count on day 7-10 and RDI in the FN group were lower than those in the non-FN group (all p<0.05). GNRI <92 and COP-NLR score of 0 are important indicators to predict patients at high risk of DCF chemotherapy-induced FN. Furthermore, FN incidence after pegfilgrastim administration had a strong effect on delayed neutrophil recovery and reduced RDI.

Meta-Analysis of Same-Day Pegfilgrastim Administration Stratified by Myelotoxic Febrile Neutropenia Risk and Tumor Type.

Pegfilgrastim is recommended to be administered at least 24 hours following the completion of chemotherapy, yet some clinicians use a same-day administration protocol. In this meta-analysis, we compared the incidence of chemotherapy-induced (febrile) neutropenia (CIN/FN) as well as CIN/FN-related chemotherapy disruptions in cancer patients provided with pegfilgrastim same-day vs. next-day. Six databases were searched for comparative studies of same-day vs. next-day pegfilgrastim administration. Fixed or random-effects meta-analyses were conducted to estimate pooled odds ratios (ORs) and 95% confidence intervals (CIs). Thirteen studies were included in this meta-analysis. The FN OR for same-day vs. next-day administration was 1.48 (95% CI = 1.06-2.08) across all cycles, attributable mainly to studies of high FN risk (OR = 2.46, 95% CI = 1.04-5.83) vs. intermediate FN risk regimens (OR = 1.41, 95% CI = 0.95-2.10), and breast cancer (OR = 3.15, 95% CI = 1.24-8.01) vs. non-Hodgkin lymphoma (NHL; OR = 1.48, 95% CI = 0.98-2.23) and gynecologic cancers (OR = 0.64, 95% CI = 0.11-3.85). Where available, ORs for first cycle of chemotherapy, grades 3 and/or 4 CIN, and chemotherapy dose delays or reductions were in line with these findings. In this independent study, same-day pegfilgrastim administration may or may not increase the likelihood of FN, grades 3 and/or 4 CIN, and chemotherapy dose reductions or delays; and this may be a function of the myelotoxicity of the regimens (elevated in high-risk but not intermediate-risk regimens) and tumor type (elevated in breast but not in NHL or gynecologic cancers). With due caution, same-day pegfilgrastim administration may be safe and beneficial in intermediate-risk regimens and selected tumor types.

Pegfilgrastim Biosimilars in US Supportive Oncology: A Narrative Review of Administration Options and Economic Considerations to Maximize Patient Benefit.

Granulocyte colony-stimulating factor (G-CSF) biologics, such as pegfilgrastim, are a standard of care in supportive cancer treatment that are administered once per chemotherapy cycle to reduce the incidence of febrile neutropenia. The high cost of these biologics in the United States can be a limiting factor to accessing care; however, lower-cost pegfilgrastim biosimilars have been available for several years for patients requiring prophylaxis of febrile neutropenia. Different options for pegfilgrastim administration are also now available to accommodate specific patient preferences. As patients may want to minimize the risk of both neutropenia and SARS-CoV-2 infection, same-day administration is a pertinent option during the present COVID-19 pandemic. Therefore, individualized, patient-centered approaches and risk-management strategies should be considered when selecting the treatment and administration method for prophylaxis of febrile neutropenia. Three methods of administration would minimize hospital or clinic visits while also providing the prophylactic effect of G-CSF: same-day administration after chemotherapy, use of the US Food and Drug Administration–approved on-body injector delivering pegfilgrastim approximately 27 h after chemotherapy, or self-administration by the patient or caregiver > 24 h after chemotherapy. Choice of the specific administration option should be based on the patient’s specific needs, while also considering mitigating factors, such as the economic burden associated with biologic medications and the risk of COVID-19. Pegfilgrastim biosimilars can minimize the additional financial burden on patients and the health care system during this pandemic and beyond.