Dose Of Pegfilgrastim Research Articles

Granulocyte colony-stimulating factor has the potential to attenuate the therapeutic efficacy of chemo-immunotherapy for extensive-stage small-cell lung cancer.

Granulocyte colony-stimulating factor (G-CSF) has the potential to attenuate the anti-tumor immune responses of T-cells by increasing immune suppressive neutrophils and myeloid-derived suppressor cells. However, the clinical impact of G-CSF on the efficacy of immunotherapy remains unknown. This multi-center retrospective analysis evaluated the impact of G-CSF in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemo-immunotherapy. We analyzed 65 patients with ES-SCLC who completed four cycles of induction chemo-immunotherapy and evaluated the effects of G-CSF on progression-free survival (PFS), overall survival (OS), and a durable response to immunotherapy (defined as PFS ≥ 12months). Fifty patients (76.9%) received ≥ 1 dose of G-CSF. The PFS of the patients with G-CSF was poorer than that of the patients without G-CSF (median PFS 8.3 vs. 4.9months, p = 0.009). The OS of the patients with G-CSF tended to be shorter, but not statistically significant, than that of the patients without G-CSF (median OS 24.3 vs. 16.4months, p = 0.137). In the multivariate analysis, G-CSF administration was associated with poorer PFS (hazard ratio 2.78, 95% CI 1.36-5.69, p = 0.005) and was identified as a determinant of a durable response (odds ratio 0.18, 95% CI 0.04-0.80, p = 0.024). These results were consistent with other definitions of G-CSF administration (administration of ≥ 1 dose of pegfilgrastim, or either ≥ 5 doses of filgrastim or ≥ 1 dose of pegfilgrastim). G-CSF has the potential to attenuate the efficacy of immunotherapy; therefore, the indication for G-CSF during chemo-immunotherapy should be carefully considered for ES-SCLC.

Abstract PO2-12-12: REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer

Abstract Background: Granulocyte colony stimulating factor (G-CSF) such as filgrastim (FIL) or pegfilgrastim (PEG) significantly reduces the risk of febrile neutropenia (FN) and treatment-related hospitalization in patients with early breast cancer receiving chemotherapy. However, patients receiving G-CSF can experience clinically significant bone pain. Previous studies examining post-GCSF bone pain were mostly based on physician pain assessment and compared mixed doses (30/60/100 μg/kg) of PEG vs. FIL (5μg/kg/day or 300 μg/day) given for 7 to 14 days. Based on a randomized non-inferiority study, 5 days of FIL is considered non-inferior to 10 days of FIL to prevent FN and hospitalizations and is frequently used in patients receiving chemotherapy for breast cancer. Patient-reported bone pain after 5 days of FIL vs. single dose of PEG has never been compared in a prospective randomized study and has important implications for patient and physician treatment preferences. Methods: In this multicenter, open-label trial, patients receiving neo-/adjuvant chemotherapy for early-stage breast cancer requiring primary FN prophylaxis with G-CSF were randomized 1:1 to either 5 days of FIL (300 μg or 480μg if ≥ 90 kg) or 1 day of PEG (6 mg) with each cycle of chemotherapy. The primary endpoint was bone pain using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) during cycle 1. We used linear regression adjusting for stratification factors [cancer center (2 centers) and chemotherapy regimen (taxane (TAX) or anthracycline (ANTH)-based during cycle 1] and prespecified baseline covariates: age, pain, and use of pain medications pre-chemotherapy. Supportive analysis of bone pain across cycles 1 to 4 was conducted using repeated linear regression. Key secondary endpoints included incidence of FN, hospitalizations, chemotherapy delay, dose-reduction or discontinuation, and chemotherapy-related deaths. Results: From June 2021 to March 2023, 233 patients were enrolled, with 217 patients (108 FIL/109 PEG) in the intention-to-treat analysis; 16 (7.4%) patients were excluded because of incomplete follow-up. Participants were mean age 55.6 years; almost exclusively female (99.1%), on chemotherapy regimen TAX 57% vs. ANTH 43%, had mean baseline pain score 1.12, and prevalence of pain medication use pre-chemotherapy was acetaminophen 14.7%, non-steroidal anti-inflammatory drugs (NSAIDs) 6.0% and opioids 3.2%. Characteristics were balanced between arms (Table 1). After repeated measures linear regression adjusted for age, chemotherapy regimen, baseline pain, and use of pain medications pre-chemotherapy, mean AUC for bone pain at cycle 1 was 10.94 for FIL and 10.12 for PEG (mean difference 0.82; 95% CI: -1.59, 3.23; p = 0.516). There was no significant difference between arms across treatment cycles (interaction p = 0.785; mean time-averaged difference 0.28; 95% CI: -1.75, 2.32). Across cycles 1 to 4, mean peak pain over 5 days post-GCSF was 3.27 vs. 3.41 (p=0.700); frequency of bone pain during first 8 days (pain score > 0) was 52.5% vs. 51.3%; p=0.358, and mean frequency of severe pain (pain score ≥ 5) was 17.5% vs. 15.2%; p=0.014 for FIL vs. PEG, respectively. The incidence of FN [4.6% vs. 0%, absolute difference 4.6% (95% CI: -0.3%, 9.5%; p=0.069)] and hospitalization [FN and non-FN related: 10.2% vs. 1.8%, absolute difference of 8.4% (95% CI: 1.2%, 15.5%; p=0.021)] was higher in the FIL group. There were no significant differences in chemotherapy delay (13% vs. 11%; p=0.815), dose reduction (14.8% vs. 14.7%; p=0.999), early discontinuation (8.3% vs. 5.5%; p=0.580), or chemotherapy-related death (0.9% vs. 0%; p=0.996) in the FIL vs. PEG groups, respectively. Conclusion: There was no difference in patient-reported bone pain after 5 days of FIL or PEG, even after controlling for important clinical factors. Importantly, the study observed higher rates of FN and hospitalizations in patients receiving FIL for 5 days only. Table 1 Baseline Characteristics Citation Format: Terry Ng, Yuxin Zhang, Carol Stober, Jennifer Shamess, Natalie Mills, Stuart Nicholls, Mohammed Ibrahim, Daniel Davoudpour, Christopher Armiento, Marie-France Savard, Moira Rushton, Arif Awan, Sandeep Sehdev, John Hilton, Xinni Song, Rakesh Goel, Fiona Macdonald, Kelly Daigle, Lisa Vandermeer, Monica Taljaard, Mark Clemons. REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-12.

Efficacy and Safety of Single-dose Pegfilgrastim for CD34 + Cell Mobilization in Healthy Volunteers: A Phase 2 Study.

Pegfilgrastim, a long-acting form of granulocyte-colony stimulating factor, with a convenient single-injection dosage, is being investigated for peripheral blood stem cell (PBSC) mobilization in healthy volunteers. However, data on the adequate dose of pegfilgrastim for PBSC mobilization are limited. This phase 2, single-arm study evaluated the efficacy and safety of pegfilgrastim for PBSC mobilization in healthy volunteers. The study comprised 2 phases: pilot (steps 1-3, dose escalation, a single subcutaneous dose of 3.6, 7.2, and 10.8 mg pegfilgrastim, respectively) and evaluation (step 4, efficacy and safety assessments). The primary endpoint was the proportion of subjects who achieved mobilization of ≥20 × 10 6 /L cluster of differentiation 34 positive (CD34 + ) cells. Thirty-five subjects (6 each in steps 1 and 2 and 23 in step 4) were included. In the pilot phase, step 3 with a 10.8 mg dose was not conducted due to favorable outcomes in step 2 (desired CD34 + cell count), at 7.2 mg pegfilgrastim, which was identified as the optimal dose for the evaluation phase. In the evaluation phase, successful CD34 + mobilization was achieved in all 23 subjects. The mean peripheral blood CD34 + cells count peaked on day 5. Back pain, thrombocytopenia, transient elevations of alkaline phosphatase, and lactate dehydrogenase were the most common adverse events. All adverse events were mild, and none led to study discontinuation. A single-dose pegfilgrastim successfully mobilized an optimal number of CD34 + cells and was well tolerated. Pegfilgrastim could be an alternative option for PBSC mobilization in healthy volunteers. The trial was registered at www.clinicaltrials.gov (NCT03993639).

Efbemalenograstim alfa not inferior to pegfilgrastim in providing neutrophil support in women with breast cancer undergoing myelotoxic chemotherapy: results of a phase 2 randomized, multicenter, open-label trial

PurposeEvaluate the safety and efficacy of efbemalenograstim alfa for neutrophil support in breast cancer patients undergoing myelosuppressive chemotherapy in a phase 2, dose-finding, open-label study (NCT01648322, ClinicalTrials.gov, 2012–07-19).Methods232 patients received up to 4 cycles of chemotherapy, 141 patients with docetaxel + cyclophosphamide (TC) and 91 patients with docetaxel + doxorubicin + cyclophosphamide (TAC). Patients were randomized to efbemalenograstim alfa (80, 240, or 320 µg/kg [TC]; 240 or 320 µg/kg [TAC]) or pegfilgrastim (6 mg) on Day 2 of each cycle.ResultsEfbemalenograstim alfa was non-inferior to pegfilgrastim in duration of moderate and severe neutropenia (absolute neutrophil count [ANC] < 1.0 × 109/L) in TAC Cycle 1 (mean [SD] of 2.1 [1.58] and 2.1 [1.46] days for 240 µg/kg and 320 µg/kg efbemalenograstim alfa, respectively, and 1.8 [1.28] days for pegfilgrastim), with a difference (95% CI) of 0.3 (-0.4, 1.1) days. ANC nadir occurred between Days 7–8 of TAC Cycle 1, with mean [SD] of 0.68 [1.064], 0.86 [1.407] and 0.78[1.283] × 109/L for 240 µg/kg, 320 µg/kg efbemalenograstim alfa and pegfilgrastim, respectively. Time to ANC recovery post nadir (defined as an ANC > 2.0 × 109/L after the expected ANC nadir) was 2.0–2.4 and 1.9 days for TAC patients treated with efbemalenograstim alfa and pegfilgrastim, respectively. No significant difference was found between any dose of efbemalenograstim alfa and pegfilgrastim in TAC Cycle 1 for incidence of moderate to severe neutropenia (76%-77% of patients) or incidence of severe neutropenia (ANC < 0.5 × 109/L; 63%-72%). Efbemalenograstim alfa exhibited similar safety profile to pegfilgrastim. Febrile neutropenia occurred in 4 (1.8%) patients, 2 patients each for 320 µg/kg efbemalenograstim alfa and pegfilgrastim, with no event considered related to study drug.ConclusionEfbemalenograstim alfa was comparable to pegfilgrastim in efficacy and safety.ClinicalTrials.gov identifierNCT01648322.

P34-2 Half dose pegfilgrastim for patients with breast cancer during chemotherapy: A case-series study

P34-2 Half dose pegfilgrastim for patients with breast cancer during chemotherapy: A case-series study

Half Dose Pegfilgrastim for Patients With Breast Cancer During Chemotherapy: A Case-series.

This study aimed to show the trend of neutrophil counts and frequency of febrile neutropenia after changing pegfilgrastim from 3.6 mg to 1.8 mg. This case-series study was performed between April 2016 and December 2021 at Hyogo Prefectural Amagasaki General Medical Center. All patients who reduced their normal dose of 3.6 mg pegfilgrastim to 1.8 mg due to adverse events or markedly elevated neutrophil counts were included. Any type of chemotherapy was acceptable. Patients who dropped out within 1 month of receiving 1.8 mg pegfilgrastim were excluded. The primary outcome was the neutrophil counts after receiving 1.8 mg pegfilgrastim. The secondary outcome was febrile neutropenia, which was evaluated by the Common Terminology Criteria for Adverse Events v5.0. The study included seven patients who used a regimen of dose-dense epirubicin and cyclophosphamide, trastuzumab, pertuzumab, and docetaxel, docetaxel, or docetaxel and cyclophosphamide. After using 1.8 mg pegfilgrastim, neutrophil counts changed from a mean of 18,944 [standard deviation (SD)=-7,768] to only 4,447 (SD=1,224). The patients experienced grades 1 to 3 adverse events during the use of 1.8 mg and 3.6 mg pegfilgrastim doses, including febrile neutropenia, and pain. Four patients (57%) complained of grade 1 or 2 fatigue and anorexia. After switching from 3.6 mg pegfilgrastim to 1.8 mg, three patients (42%) experienced adverse events. In patients who experienced adverse events due to markedly elevated neutrophil counts with pegfilgrastim, reducing the dose of pegfilgrastim by half may reduce adverse events.

Cost comparison of filgrastim versus pegfilgrastim and pegfilgrastim biosimilars for inpatient prophylaxis of febrile neutropenia.

The Ohio State University Comprehensive Cancer Center (The James) uses daily subcutaneous filgrastim as the inpatient granulocyte colony-stimulating factor of choice. The coordination of care associated with filgrastim can often be a barrier to patient discharge. The purpose of this study was to compare the inpatient cost of daily filgrastim to single dose pegfilgrastim and biosimilars. Adult patients admitted to The James who received at least one dose of filgrastim between June 1, 2021 and August 31, 2021 were retrospectively identified. This study compared the inpatient cost of filgrastim and biosimilars associated with one chemotherapy cycle to the potential inpatient cost of pegfilgrastim and biosimilars based on average sales price (ASP). Additionally, the number and duration of discharge prescriptions for filgrastim was determined. Of the 44 unique patient encounters that met inclusion criteria, 19 received 300-mcg doses of filgrastim and 25 received 480-mcg doses. The median number of doses administered per admission was eight. If each of these patients were to instead receive the most inexpensive biosimilar, pegfilgrastim reference product, the cost would be 216% higher than with filgrastim-sndz. At discharge, 15 patients (34%) received a prescription for filgrastim to be continued for a median duration of 6 days. Based on ASP, pegfilgrastim was more costly than filgrastim. Potential rebates and negotiation power may alter the financial outlook of adding pegfilgrastim to inpatient formulary. Exploration of delays in discharge due to insurance coordination for filgrastim continuation in the outpatient setting may also impact formulary decisions.

Model-Based Approach to Selecting Pegfilgrastim Dose for Pharmacokinetic and Pharmacodynamic Similarity Studies in Biosimilar Development.

This study applied modeling and simulation (M&S) approaches to evaluate the sensitivity of pegfilgrastim pharmacokinetics (PKs) and pharmacodynamics (PDs) to changes in dose amount, and linear or nonlinear clearance (CL) over pegfilgrastim subcutaneous dose of 2-6 mg. A previously published model was adapted to better describe pegfilgrastim PK and PD data in healthy subjects and used in simulation. Nonlinear CL accounts for 98% and 77%, respectively, of the total CL of pegfilgrastim at 2 and 6 mg. The sensitivity analyses showed: (i) PK of 2 and 6 mg doses are similarly sensitive to detect differences for a 5% change in dose; (ii) PK of 2 mg dose is more sensitive to changes in receptor binding affinity, a model parameter for nonlinear CL, and a product quality attribute characterized with orthogonal methods as part of demonstrating analytical similarity between products; (iii) PK of approved 6 mg dose is more sensitive to changes in linear CL, which has not been associated with any specific product quality attributes, and (iv) the PDs are not sensitive to changes in linear or nonlinear CL. Taken together, our analyses support that the approved pegfilgrastim dose of 6 mg is appropriate for detecting differences between a biosimilar and the reference products in pegfilgrastim PK and PD similarity studies. The described M&S approaches can be adopted to support dose selection for biosimilars with nonlinear PK and complex PK-PD interplay.

Single-Center Analysis of Pegfilgrastim-induced Aortitis Using a Drug Prescription Database and CT Findings.

Background Pegfilgrastim-induced aortitis is a rare but serious adverse event in patients undergoing anticancer therapy with granulocyte colony-stimulating factor analogs. Despite previous case series and systemic reviews, the exact incidence, clinical presentation, and CT manifestations of pegfilgrastim-induced aortitis remain unclear. Purpose To clarify the incidence and clinicoradiologic characteristics of pegfilgrastim-induced aortitis. Materials and Methods Pegfilgrastim administration records from January 2015 to March 2021 were retrospectively collected from the drug prescription database of a single center and were matched with the relevant findings in the CT database. Corresponding CT images within 6 months were available for a total of 1462 doses of pegfilgrastim in 674 patients. Four radiologists reviewed the CT images for the presence of aortitis in two steps. Clinical information and the distribution of aortitis on CT images were examined for patients with a diagnosis of pegfilgrastim-induced aortitis. Results Pegfilgrastim-induced aortitis was observed in 18 of 674 patients (mean age, 62 years ± 13 [SD]; 424 men), resulting in incidence rates of 2.7% per patient (95% CI: 1.6, 4.2) and 1.2% per dose (95% CI: 0.7, 1.9). The most common original primary malignancies were esophageal cancer (n = 10, 9%), breast cancer (n = 3, 4%), and pancreatic cancer (n = 2, 2%). The most common anticancer drugs used at onset were 5-fluorouracil, cisplatin, and docetaxel. Seven cases were symptomatic, while the remaining 11 (61%) were asymptomatic. CT findings indicated that aortitis involved branches of the aortic arch in 13 cases (72%), aortic arch in 10 cases (56%), and abdominal aorta in two cases (11%). Conclusion Pegfilgrastim-induced aortitis may be more prevalent than previously reported and may be more common in patients with esophageal cancer and those who received 5-fluorouracil, cisplatin, and docetaxel as anticancer drugs. The findings also suggest that pegfilgrastim-induced aortitis is often characterized by aortic arch and proximal branch involvement at CT. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Krinsky in this issue.

Comparison of Short Acting versus Long Acting Filgrastim for Reduction of Chemotherapy Induced Febrile Neutropenia

Introduction: Febrile neutropenia (FN) is the most frequent complications reported during cytotoxic chemotherapy treatment. Granulocyte colony stimulating factor (GCSF) is used to reduce neutropenia and related complications. This study compares short versus long acting filgrastim for reduction of chemotherapy induced FN. Methods: Histologically confirmed solid cancer patients (n=112) receiving either high risk or intermediate risk chemotherapy regimens for FN were randomized into two groups. Group one received filgrastim 300 mcg subcutaneously for five days and group two received pegfilgrastim 6 mg subcutaneously single dose, starting after 24 hours after completion of chemotherapy during each chemotherapy cycle. The primary end point was the occurrence of FN. The secondary end points were number of hospital visits, duration of hospital stay and total direct costs of filgrastim and pegfilgrastim. Results: Fifty six patients were analyzed in each group. The incidence of FN was significantly lower in pegfilgrastim group (42.90%) than filgrastim group (69.6%), p&lt;0.004. The mean hospital visits were 1.84±1.93 in filgrastim group and 0.84±1.19 in pegfilgrastim group with 58.90% and 33.90% hospital admission respectively in both groups. The mean duration of stay was 4.14±3.69 days in filgrastim group and 2.36±3.35 days in pegfilgrastim group. The mean cost (Nepali rupees) of filgrastim and pegfilgrastim was 20162.50+6645.37 (US$168.17±55.42) and 32210.71±10429.43($268.67±86.99) respectively. Conclusion: Single dose of pegfilgrastim was significantly better than multiple doses of filgrastim for reducing FN incidence in cancer patients receiving chemotherapy.

Real-world safety and supportive care use of second-line 5-fluorouracil-based regimens among patients with metastatic pancreatic ductal adenocarcinoma

Objective Chemotherapy-related adverse events (AEs) can negatively impact the care of patients. The prevention and management of AEs often require additional medications. This study evaluated the percentages of patients with metastatic pancreatic ductal adenocarcinoma (mPDAC) undergoing second-line therapy with 5-fluorouracil (5-FU)-based regimens that experienced AEs during treatment and received medication to manage those AEs. Methods We conducted a retrospective observational analysis utilizing the Flatiron Health database of adult patients with mPDAC who started second-line therapy between January 2016 and August 2020. The occurrence of diarrhea, fatigue, nausea and vomiting, neuropathy, and hematologic AEs including G3/G4 anemia, neutropenia, and thrombocytopenia was assessed. The use of concomitant medications including atropine and granulocyte colony stimulating factor (G-CSF) was assessed. Results Of the 825 eligible patients, 29.0% (n = 239) received FOLFIRINOX, 24.0% (n = 198) received FOLFOX, 6.8% (n = 56) received FOLFIRI, and 40.2% (n = 332) received liposomal irinotecan-based regimens. FOLFIRI and FOLFIRINOX regimens were associated with the highest rates of anemia (16.1% and 15.5%), neutropenia (19.6% and 22.6%), and thrombocytopenia (14.3% and 9.6%). The liposomal irinotecan and FOLFOX regimens were associated with lower rates of anemia (11.8% and 12.1%), neutropenia (12.4% and 14.7%), and thrombocytopenia (2.4% and 8.1%). G-CSF use was observed among 63.6%, 34.9%, 33.9%, and 44.9% of patients treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Diarrhea was observed among 12.5%, 4.5%, 12.5%, and 10.2% of patients who were treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Nausea and vomiting occurred in 14.9%, 12.6%, 10.5%, and 13.1% of patients treated with FOLFIRINOX, FOLFOX, FOLFIRI, and liposomal irinotecan-based regimens, respectively. Atropine use was higher in patients treated with FOLFIRINOX and FOLFIRI (90.8% and 94.6%, respectively) than in patients treated with liposomal irinotecan-based regimens (75.6%). Conclusions In patients with mPDAC who received second-line therapy, those who received liposomal irinotecan-based regimens had the lowest rates of anemia, neutropenia, and thrombocytopenia compared to FOLFIRI, FOLFIRINOX, and FOLFOX, while requiring a similar or lower level of medication to treat and manage those adverse events. Patients treated with FOLFIRI received the highest dose of pegfilgrastim to manage neutropenia. The results of this real-world analysis are consistent with prior evaluations of patients with mPDAC and highlight the importance of managing adverse events and associated cost implications.

Evaluation of a novel medical device for pegfilgrastim administration.

Pegfilgrastim, a pegylated form of granulocyte colony‐stimulating factor, has reduced the risk of developing febrile neutropenia, which is associated with an increase in severe infection and prolonged hospitalization. However, pegfilgrastim administration requires that patients visit hospital following cancer chemotherapy, thus imposing a burden on patients and those around them. An on‐body injector (OBI), which automatically administers pegfilgrastim about 27 hours after chemotherapy, was used in this study. The OBI, which consists of a main pump unit and infusion set, is a drug delivery device designed to be attached to the patient's body, with a timer‐controlled dosing function. This study was conducted in breast cancer patients to evaluate the safety of pegfilgrastim administered subcutaneously via the OBI. The study period consisted of screening and treatment observation periods involving four cycles of neoadjuvant or adjuvant chemotherapy with docetaxel plus cyclophosphamide. One 3.6‐mg pegfilgrastim dose was administered subcutaneously via OBI during each cycle of chemotherapy. The study enrolled 35 patients, and no serious adverse events or febrile neutropenia occurred. Administration of pegfilgrastim was successfully completed at all times when the OBI was attached to the patient, and no safety concerns associated with OBI function arose. For outpatients requiring pegfilgrastim following cancer chemotherapy, the use of an OBI was considered to be a safe option to reduce the need for outpatient visits that restrict their activities of daily living.

Abstract OT2-21-01: A randomized, multicenter pragmatic trial comparing bone pain from a single dose of pegfilgrastim to 5 doses of daily filgrastim in breast cancer patients receiving neoadjuvant/adjuvant chemotherapy (REaCT-5G)

Abstract Background: Current guidelines recommend the use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis to prevent febrile neutropenia (FN) associated with commonly used breast cancer chemotherapy regimens. Filgrastim (FIL) is a short-acting G-CSF injection that requires daily subcutaneous injection starting 24-72 hours after chemotherapy for 5 to 10 days. Pegfilgrastim (PEG) is a long-acting, pegylated formulation that requires a single injection 24-72 hours after chemotherapy. G-CSF causes bone pain in approximately 70% of patients, which can be severe in over 25% of cases. While registration trials for PEG showed bone pain from PEG was comparable to FIL when given for a median duration of 11 days, many oncologists are now only prescribing FIL for 5 days based on a multicenter RCT showing that 5 days of FIL is non-inferior to 7 or 10 days of FIL in terms of FN and treatment-related hospitalizations. Furthermore, the cost of 5 days of FIL ($CA 721.55 for 300 mcg dose) is half of the price of a single dose of PEG ($CA 1424.63). Therefore, if 5 days of FIL leads to significantly less bone pain, this may improve health-related quality of life (HR-QoL) for patients, improve adherence to G-CSF, and improve cost-effectiveness. Methods: Patients receiving neo-/adjuvant chemotherapy for early stage breast cancer requiring primary FN prophylaxis with G-CSF will be approached for this pragmatic, multicenter, open-label superiority RCT. Using the Rethinking Clinical Trials (REaCT) methodology that incorporates an integrated oral consent model, eligible and consented patients will be randomized to either 5 days of FIL or one day of PEG with each cycle of chemotherapy. The primary endpoint is bone pain during the first 5 days after G-CSF injection using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) of the Bone Pain Diary. Secondary endpoints include incidence of FN and treatment-related hospitalizations, incidence of chemotherapy delay, dose-reduction, or discontinuation, incidence of chemotherapy-related mortality, rate of G-CSF compliance, healthcare resource utilization, HR-QoL, and cost-effectiveness. Participants will also complete a Treatment Preference Questionnaire (TPQ) exploring the relative importance of different factors in deciding between PEG vs. 5 days of FIL both before randomization and at the end of the study. To achieve 80% power in an ANCOVA analysis and assuming 5% are loss to follow-up, the planned sample size is 232 patients (116 per arm). The randomization (1:1 ratio) will be stratified by treatment center (4 centers) and chemotherapy regimen (taxane-based vs. anthracycline-based in the first 4 cycles). Results: The study opened for enrollment on June 9, 2021. As of July 6, 2021, the study has opened at one site, and 13 patients have been randomized.Conclusion: This will be the first RCT using a patient-reported Bone Pain Diary that was co-developed by patient partners to measure bone pain between 5 days of FIL vs. PEG. In collaboration with patient partners, the study incorporates a tool (TPQ) that explores factors that may be important in deciding between PEG and FIL, with the aim of translating the findings of this study into real world clinical practice. Citation Format: Terry L. Ng, Monica Taljaard, Marie-France Savard, Carol Stober, Stuart Nicholls, Lisa Vandermeer, Kednapa Thavorn, Claudia Hampel, Jennifer Shamess, Natalie Mills, John F. Hilton, Mark Clemons. A randomized, multicenter pragmatic trial comparing bone pain from a single dose of pegfilgrastim to 5 doses of daily filgrastim in breast cancer patients receiving neoadjuvant/adjuvant chemotherapy (REaCT-5G) [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr OT2-21-01.

Stem‐cell mobilization of healthy sibling donors with pegfilgrastim—A prospective open‐label phase II trial (EudraCT no: 2005‐004971‐39)

Pegfilgrastim is a covalently bound conjugate of filgrastim and mono-methoxypolyethylene glycol with a longer half-life. We report on phase II prospective monocentric trial examining the feasibility of stem cell mobilization with 12 mg single dose pegfilgrastim in related donors. The objectives were to determine the optimal collection day, defined as CD34+ concentration in peripheral blood (PB) >50 cells/μl, the number of donors collected with single leukapheresis, and the peak level of pegfilgrastim in donor-serum. Furthermore, the cell composition of grafts was assessed and compared to published data. The results included about 28 matched related donors. The median pegfilgrastim serum level remained >200 ng/mL for 48 hours before declining, with the maximal measured concentration of 259.49 ng/ml 24 h after application. The median white blood cell count and CD34 count in PB peaked on day four with 52.6 (range 22.8-85.0) Gpt/l and 66.25 (range 22.9-136.6) cells/μl, respectively. A CD34+ count >50 cells/μl on day four was detected in 75% of donors. 79% of the donors underwent a single collection. Conventional filgrastim was administered additionally in two donors, due to insufficient CD 34+ concentration in PB. 89% of donors showed CD34+ yields ≥4 (median 6.5, range 4.6-14.5) × 10/kg body weight of the recipient. All grafts were administered without rejections. The results of this trial showed that stem cell mobilization with pegfilgrastim is a feasible, and attractive option. This is the first trial presenting the kinetics of pegfilgrastim serum levels in healthy donors.

Comparative Cost-Efficiency Analysis of Granulocyte Colony-Stimulating Factors for Use in Chemotherapy Patients in the United States

Introduction: Granulocyte colony-stimulating factors (G-CSFs), when used to reduce the incidence, severity, and duration of febrile neutropenia (FN) in chemotherapy patients, may subsequently reduce direct medical costs associated with FN by reducing rates of hospitalization, serious infections, and the use of broad-spectrum antibiotics. While the cost per chemotherapy cycle for short-acting G-CSFs (ie, filgrastim [Neupogen®], filgrastim-sndz [Zarxio®], and tbo-filgrastim [Granix®]) depends on the frequency and number of doses administered and dose used (ie, 300 mcg or 480 mcg), the cost for the long-acting G-CSF pegfilgrastim (Neulasta® 6 mg) is relatively consistent, as it is dosed once per chemotherapy cycle and is effective for 14 days. Given this difference, the extent and duration required for short-acting G-CSF treatment determine the cost-efficiency of these agents relative to pegfilgrastim, when considering similar efficacy and safety across products. This cost-efficiency analysis evaluated the effective daily cost of G-CSFs per chemotherapy cycle, from a US payer perspective.Methods: An interactive model was developed to simulate the relative cost for one chemotherapy cycle from 1 to 14 days for all currently marketed G-CSF products indicated to decrease the incidence or reduce the duration of FN in patients with non-myeloid malignancies treated with myelosuppressive chemotherapy. All agents were assumed to be provided at the health care provider (HCP) office, purchased through the patient's medical benefit, and administered by the HCP. An administration cost for each injection was included. Base-case data were derived from publicly available resources. Daily cost for short-acting G-CSFs was calculated using single dose drug acquisition cost and one administration fee per day, while daily cost for pegfilgrastim was calculated using the drug acquisition cost for one injection plus one administration cost. Additionally, the acquisition cost for short-acting agents was weighted according to the national utilization for low- (300 mcg) vs high-dose (480 mcg) products.Results: The cost of tbo-filgrastim treatment ranged from $312.96 (1 dose) to $4381.47 (14 doses), the cost of filgrastim-sndz treatment ranged from $351.30 to $4918.23, and the cost of filgrastim treatment ranged from $475.24 to $6653.33, compared with $4527.93 for one injection of pegfilgrastim. Tbo-filgrastim is cost-efficient compared with pegfilgrastim through 14 doses. Pegfilgrastim becomes cost-efficient compared with filgrastim-sndz at 13 doses and with filgrastim at 10 doses.Conclusion: Real-world data suggest that short-acting G-CSF products are used fewer than 14 days per chemotherapy cycle in clinical practice, while one dose of pegfilgrastim is efficacious for 14 days. Using acquisition costs plus administration costs for the injections, without considering the additional impact of health plan-contracted rates and manufacturer rebates for the drugs themselves, tbo-filgrastim is cost-efficient for a complete 14-day chemotherapy cycle compared with pegfilgrastim, while filgrastim-sndz and filgrastim are cost-efficient compared with pegfilgrastim through 12 doses and 9 doses, respectively. That is, short-acting products are more cost-efficient than pegfilgrastim in any chemotherapy cycle if fewer than 10 doses are needed. This finding assumes equal efficacy and safety among G-CSFs, and that all other chemotherapy-related patient characteristics are otherwise equal, including clinical appropriateness of prescribed duration of short-acting G-CSFs. G-CSFs reduce FN-associated direct medical costs and may differ in their ability to further reduce total direct medical costs of care for chemotherapy-treated patients when daily cost is considered in conjunction with necessary days of therapy. [Display omitted] DisclosuresJames:Teva Pharmaceuticals: Consultancy. Trautman:Teva Pharmaceuticals: Consultancy. Szabo:Teva Pharmaceuticals: Employment. Tang:Teva Pharmaceuticals: Employment.

Feasibility and Kinetics of CD34+ Hematopoietic Cells Mobilization By Low-Dose Pegfilgrastim in Lymphoma Patients

▪Introduction: Hematopoietic stem cell rescue with autologous peripheral blood stem cells (PBSC) following high-dose chemotherapy has been used for the treatment of lymphoma and myeloma. Granulocyte colony-stimulating factor (G-CSF) is used for PBSC mobilization but data on PBSC mobilization by pegfilgrastim is limited. Recent studies showed successful PBSC harvest by single dose of pegfilgrastim given at 6mg or 12mg within 4 days after chemotherapy in patients with malignant lymphoma. However, administration of pegfilgrastim early after chemotherapy administration induces overshoot of neutrophils, which may result in rapid plasma clearance of G-CSF due to internalization of the G-CSF/G-CSF receptor complexes via endocytosis in neutrophils. Previous studies demonstrated that day 7 injection of pegfilgrastim in the course of chemotherapy mitigated the neutrophil overshoot compared to day 4 injection of pegfilgrastim. We hypothesized that day 7 administration of lower dose 3.6mg pegfilgrastim could avoid neutrophil overshoot and efficiently mobilize PBSCs. Here we show the kinetics of CD34+ PBSC mobilization after 3.6mg pegfilgrastim given on day 7 in the course of chemotherapy.Patients and Methods: Between February 2016 and May 2017, twenty patients with malignant lymphoma enrolled in this study (14 DLBCL, 2 AITL, 2 ALCL, 1 ATLL, 1 FL). Median age was 54 (range 30-65). Eight patients had clinical stage III-IV. Median number of prior chemotherapy was 0 (range 0-2). All patients received cytotoxic chemotherapy (13 CHOP, 2 DeVIC, 2 ESHAP, 1 DHAP, 1 EPOCH, 1 HD-AraC) on day 1 and 3.6mg of pegfilgrastim was administered subcutaneously on day 7. Peripheral blood CD34+ cell counts were analyzed from day 11 to 14 after chemotherapy by flowcytometric analysis using single platform method based on ISHAGE guideline. The primary objective is to clarify the kinetics of peripheral blood CD34+ cells without harvesting intervention. CD34+ values on each time point is statistically tested using one-sample t-test. To visualize the primary result, bar graph with mean and its confidence interval on each day is represented with the reference line (Figure). The secondary objectives are to search peak point of CD34+ cell counts after each chemotherapy regimen and the feasibility of pegfilgrastim administration on day 7. Successful mobilization was defined as to achieve more than 10×106/L peripheral blood CD34+ cells on any time points between day 11 and 14. All patients were assessed for toxicity according to the National Cancer Institute Common Toxicity Criteria, version 4.0. This study was approved by the institutional review board and conducted in accordance with the Declaration of Helsinki.Results: Successful mobilization was achieved in 19 of the 20 patients (95%). Mean number (SD) of WBC (×109/L) on each day between day 11 and day 14 was 5.4 (3.7), 11.4 (9.1), 14.2 (9.1) and 13.9 (7.4), respectively. Mean number (SD) of CD34+ cells (×106/L) on each day between day 11 and day 14 was 20.3 (22.5), 38.0 (35.7), 40.3 (39.8), and 40.1 (53.5), respectively. The 98.75% confidence interval [CI] of CD34+ cells (×106/L) on each day between day 11 and day 14 was [6.39-34.22], [16.16-60.25], [15.77-64.97] and [7.09-73.16], respectively (Figure). The number of CD34+ cells on day 12 or 13 showed significantly higher than 10×106/L CD34+ cell (P = 0.0022 and 0.0030, respectively) (Figure). We then compared the peak of CD34+ cells in a peripheral blood in each chemotherapy regimens. The peak day of CD34+ cell in patients who received CHOP regimen was day 13 (mean 54.3 ×106/L, range 15.8-151.0×106/L) . However, in 4 of 5 patients who received platinum containing regimen, CD34+ cells failed to reach the peak before day 14 because of prolonged myelosuppression. The number of prior chemotherapy regimen (0 vs 1-2) was not associated with the kinetics of CD34+ cells (p = 0.35). No infectious events including febrile neutropenia were observed. Pain and LDH elevation (Grade 1-2) were the main adverse events related to pegfilgrastim administration. We had not detected any severe adverse events.Conclusion: Our data indicated that 3.6mg pegfilgrastim on day 7 can efficiently mobilize CD34+ cells to peripheral blood without any severe adverse events. [Display omitted] DisclosuresTeshima:Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Astellas: Research Funding; Kyowa-Hakko Kirin: Research Funding; Pfeizer: Research Funding; Chugai: Research Funding; Bristol-Myers Squibb: Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

Autologous Hematopoietic Progenitor Cells Mobilization with Combination of Pegfilgrastim and Plerixafor: Efficacy and Cost Assessment

Introduction: Filgrastim (FIL), administered as 4 or more daily multi-vial subcutaneous injections is the most commonly utilized growth factor for mobilization of autologous hematopoietic progenitor cells (auto-HPC) for transplantation. Plerixafor, a CXCR4 inhibitor, potentiates the effect of FIL by increasing the pool of circulating CD34+ cells and apheresis yield. Pegfilgrastim (PEG) is a long acting modification of FIL. Prior experience indicates that single fixed dose PEG can be utilized for auto-HPC mobilization with at least similar performance compared to daily, weight-based dose FIL, but cost is a concern.Methods: We adopted a standardized mobilization protocol consisting of PEG 6 mg on day 1, plerixafor 240 mcg/kg on day 3 and collection of auto-HPC by apheresis on day 4. When CD34+ collection target (3 x 106 CD34+/kg for patients collecting for 1 transplant and 6 x 106 CD34+/kg for patients collecting for 2 transplants) was not met on the first day of collection, evening plerixafor administration followed by next-day collection was repeated until target met or a maximum of 3 collections. Auto-HPCs were collected by apheresis with processing of approximately 3 blood volumes utilizing Cobe® Spectra or AmicusTM machine. Mobilization failure was defined as a collection < 2 x 106 CD34+/kg, considered the minimum cell dose for one transplant procedure. We prospectively collected information on mobilization outcomes for 164 consecutive auto-HPC mobilizations. We compared the estimated cost of mobilization drugs with PEG vs. simulated cost with FIL or tbo-filgrastim (TBO) at dose of 10 mcg/kg/day administered for 4 days prior to first collection and daily until collection completion, with this regimen assumed to be of similar efficacy than PEG. Drug costs were estimated using average sales price (ASP): PEG $4,191.34/ 6mg, FIL $1.009/ 1mcg, TBO $0.665/ 1mcg, and plerixafor $312.10/ 1mg. Actual body weight was used for estimation of FIL and TBO dose.Results: Among the 164 consecutive patients, 11 had the diagnosis of Hodgkin lymphoma, 20 non-Hodgkin lymphoma and 133 multiple myeloma or another plasma cell dyscrasia. Median age of patients was 60 years (range 21-73) and 92 (56%) were men. Median weight of patients was 84kg (range 51-175). Among the patients with a plasma cell dyscrasia, 87 (65%) had received prior lenalidomide, an agent known to impair HPC mobilization. Overall 4 patients (2.4%) had mobilization failure. One hundred and forty-two (87%) met the pre-established target while 18 (11%) collected enough CD34+ cells to proceed to transplant but fewer cells than pre-established target. The median CD34+/mm3 in peripheral blood on the first day of collection was 71 (range 2-481). The median collection yield on the first day was 6.06 x 106 CD34+/kg (range 0.34-39.60) and median total collection yield was 4.52 x 106 CD34+/kg (range 0.81-18.60) for patients with target of 3 x 106 CD34+/kg and 7.97 x 106 CD34+/kg (range 0.34-39.60) for patients with target of 6 x 106 CD34+/kg. Overall 77 (47%) patients had 1 day, 65 (40%) had 2 days and 22 (13%) had 3 days of collection. For patients requiring multiple days of collection, there was no substantial day-by-day decline in apheresis yield. In fact, median yield on days 2 and 3 were 106% and 97% of yield from day 1. There were no severe adverse toxicities from the mobilization regimen. All patients who have undergone transplantation successfully engrafted neutrophils and platelets. Average estimated cost of mobilization drugs with PEG + plerixafor was $14,588, comparable to estimated cost for FIL + plerixafor ($15,399) and TBO + plerixafor ($13,693). Since FIL and TBO are dosed daily and dose is weight-based, the cost comparison with PEG is greatly influenced by patient weight and number of apheresis sessions required (Figure).Conclusion: PEG plus plerixafor is a convenient, safe, effective and predictable regimen for auto-HPC mobilization. In this setting, PEG cost is comparable to FIL or TBO, being potentially cost-saving in heavier patient. [Display omitted] DisclosuresSaad:Actinium: Consultancy; Spectrum: Honoraria.

Use of Pegfilgrastim in Japanese Pediatric Patients With Solid Tumors: A Retrospective Analysis.

There are no detailed analyses of regarding pegfilgrastim usage in Japanese pediatric solid tumor patients. The approved dose of pegfilgrastim in Japan is 3.6 mg. We retrospectively evaluated the incidence of dose delays and dose reductions due to neutropenia in pediatric patients with solid tumors receiving chemotherapy with pegfilgrastim between 2015 and 2018. The effects of the timing of pegfilgrastim administration were evaluated. In chemotherapies administered every 2 and 3 weeks, prolongation of chemotherapy cycles was analyzed. Fifty-nine patients received chemotherapy with prophylactic pegfilgrastim for a total 247 cycles. No significant incidence of dose delays was observed with pegfilgrastim administration during the first 1 to 3 days after chemotherapy. When 77 cycles in 2-week regimens were compared with 166 cycles in 3-week regimens, mean cycle durations were 15.19±2.06 and 21.97±2.88 days, respectively (P<0.001). A total of 77 chemotherapy cycles administered every 14 days were subdivided. The incidence of dose delays in pediatric patients receiving chemotherapy for 5 consecutive days was similar to that for 1 day and 2 consecutive days. Pegfilgrastim prophylaxis could be of use for Japanese pediatric patients with solid tumors receiving chemotherapy, including administration every 2 weeks. Its use aids in maintaining the chemotherapy schedule.

Effect of 3 mg versus 6 mg pegfilgrastim on the prevention of febrile neutropenia in breast cancer patients receiving docetaxel and cyclophosphamide: a retrospective study.

An ECCOPG (Eastern China Cooperative Oncology Pharmacy Group) funded study was designed to compare the effect of 3 versus 6 mg pegfilgrastim for primary prevention of febrile neutropenia (FN) in Chinese breast cancer patients retrospectively. Patients undergoing a docetaxel and cyclophosphamide chemotherapy regimen, followed by pegfilgrastim, for primary prevention during 2018 and 2020 were retrospectively enrolled in the present study. The patients were divided into 2 groups according to the dose of pegfilgrastim. The incidence of severe neutropenia (absolute neutrophil count <0.5×109/L), incidence of FN, and recovery time were calculated to compare the efficacy of different groups. P<0.05 was considered statistically significant. A total of 295 patients were enrolled, 150 in the 3 mg pegfilgrastim group and 145 in the 6 mg pegfilgrastim group. No significant differences were found in the incidence of severe neutropenia (3 vs. 6 mg, 39.3% vs. 34.5%, P=0.401) and the incidence of FN (3 vs. 6 mg, 7.3% vs. 8.3%, P=0.830). Median recovery time was 2 days for both groups (P=0.485). 3 mg pegfilgrastim may be effective and safe for Chinese breast cancer patients as the primary prevention for FN. Prospective studies are needed to further confirm the prophylactic effect of 3 mg pegfilgrastim.

Effects of filgrastim versus pegfilgrastim on outcomes of DA-R-EPOCH for non-Hodgkin's lymphoma.

Our study aimed to compare the median and average last dose level reached with DA-R-EPOCH, which includes the chemotherapy agents etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin, and rituximab, in patients using filgrastim versus pegfilgrastim as febrile neutropenia primary prophylaxis. A retrospective, single-center chart review from January 1, 2014, to September 30, 2019, at The University of Kansas Health System identified patients > 18 years old who received at least four cycles of DA-R-EPOCH in an inpatient or outpatient setting for any subtype of lymphoma along with at least one dose of filgrastim or pegfilgrastim. Data was collected to compare dosing levels reached, appropriate discontinuation of daily filgrastim when ANC > 5000 cells/mm3, completion of at least twice weekly complete blood count (CBC) monitoring after chemotherapy administration, the incidence of infections, FN, hospitalizations from infections or FN, and bone pain. We hypothesized that patients receiving pegfilgrastim will achieve similar median and average dose levels of DA-EPOCH, event-free survival rates, overall response rates, completion of at least twice weekly CBC monitoring, and incidence of infections, FN, hospitalizations for infections or FN, and bone pain compared to patients receiving filgrastim. The use of pegfilgrastim as a supportive care agent resulted in similar efficacy and safety outcomes compared to filgrastim with DA-R-EPOCH in terms of dose intensity levels and incidence of infections, FN, and bone pain.