Pegylated Recombinant Human Granulocyte Colony-stimulating Factor Research Articles

A case of acute lung injury in a peripheral blood stem cell donor mobilized with pegylated recombinant human granulocyte colony-stimulating factor.

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) has been introduced for the mobilization of peripheral blood stem cells (PBSCs). However, no cases of acute lung injury (ALI) in healthy donors have been reported, and the underlying mechanisms remain poorly understood. We first reported a case of ALI caused by PEG-rhG-CSF in a healthy Chinese donor, characterized by hemoptysis, hypoxemia, and patchy shadows. Ultimately, hormone administration, planned PBSC collection, leukocyte debridement, and planned PBSC collection resulted in active control of the donor's ALI. The donor's symptoms improved without any adverse effects, and the PBSC collection proceeded without incident. Over time, the lung lesion was gradually absorbed and eventually returned to normal. PEG-rhG-CSF may contribute to ALI in healthy donors via mechanisms involving neutrophil aggregation, adhesion, and the release of inflammatory mediators in the lung. This case report examines the clinical manifestations, treatment, and mechanism of lung injury induced by PEG-rhG-CSF-mobilized PBSCs.

Abstract PO4-20-02: A prospective, randomized, controlled clinical trial comparing different PEG-rhG-CSF administration times to treat chemotherapy-induced neutropenia and febrile neutropenia in early breast cancer

Abstract Background: Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) injection time is still referred as recombinant human granulocyte CSF (rhG-CSF) as a treatment for preventing febrile neutropenia (FN) in patients with early breast cancer. The trial examined whether PEG-rhG-CSF injection on day 7 following chemotherapy was superior to injection on day 3. Patients and methods: Patients with early breast cancer were randomly assigned to receive a preventive injection on days 7 or 3 following chemotherapy. The experimental group (n = 80) received PEG-rhG-CSF treatment on day 7 after chemotherapy, whereas the control group (n=80) received it on day 3. The occurrence of grades 3–4 neutropenia and FN was the primary endpoint. The secondary endpoint was the frequency of PEG-rhG-CSF dose reduction. Results: Compared with the control group, the white blood count (WBC) or absolute neutrophil count (ANC) in the experimental group was higher on days 9 and 13 (P < 0.05) after chemotherapy, and the incidence of grade 3–4 neutropenia was lower (P = 0.038). The experimental group met the standard for lowering the PEG-rhG-CSF dose were more than that in the control group (69.74% vs. 35.06%, P < 0.001). Patients receiving a lower PEG-rhG-CSF dose had higher WBC count and ANC after chemotherapy, but were more likely to suffer from mild arthralgia. (P < 0.05). Conclusion: In comparison with PEG-rhG-CSF injection on day 3 after chemotherapy, the incidence of grade 3–4 myelosuppression is lower, and the safety is more manageable after the injection on day 7. Thus, more patients will receive dose reduction and lower patient medical costs. Citation Format: Xiaoming Zha, Jue Wang, Yinggang Xu, Jinzhi He, Ye Wang, Weiwei Zhang, Xinyu Wan, Wenjie Shi. A prospective, randomized, controlled clinical trial comparing different PEG-rhG-CSF administration times to treat chemotherapy-induced neutropenia and febrile neutropenia in 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 PO4-20-02.

Clinical Analysis of PEG-rhG-CSF in Mobilization of Autologous Hematopoietic Stem Cells in Hematological Tumors

To investigate the efficiency and optimal time of stem cell apheresis mobilized by pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in autologous stem cell transplantation (ASCT) for hematological malignancies without monitoring pre-collection CD34+ cells. Forty-six patients underwent stem cell mobilization were retrospectively analyzed between August 2017 and January 2022 at the First Affiliated Hospital of Fujian Medical University. 27 patients using high dose chemotherapy combined with PEG-rhG-CSF mobilization were enrolled in the PEG-rhG-CSF group, and other 19 patients mobilized with recombinant human granulocyte colony stimulating factor (G-CSF) were enrolled in G-CSF group. The mobilization and collection effects of the patients in two groups were compared. A total of 46 patients underwent 86 apheresis procedures, the median amount of mononuclear cell (MNC) in the PEG-rhG-CSF group and G-CSF group was 6.54（3.85-12.61）×108/kg and 6.15（1.13-11.58）×108/kg, respectively (P >0.05), the total CD34+ cells of the grafts were 11.44(1.33-65.02)×106/kg and 4.95(0.30-24.02)×106/kg (P < 0.05), with harvest timing of 14(10-20) days and 14(4-22) days, respectively (P >0.05). In the PEG-rhG-CSF group, there was a significant difference between the number of CD34+ cells collected when white blood cells (WBC) ≥10×109/L and WBC<10×109 /L, 19.04(2.85-65.02)×106/kg and 6.22(0.81-34.86)×106/kg, respectively (P < 0.05). Stem cells mobilization with PEG-rhG-CSF was highly efficient with a median mobilization time of 14 days. In the absence of peripheral blood CD34 monitoring, peripheral blood WBC≥10×109/L can be considered as a threshold for a single stem cell apheresis to collect sufficient stem cells.

On-Demand Plerixafor Added to High-Dose Cyclophosphamide and Pegylated Recombinant Human Granulocyte Colony-Stimulating Factorin the Mobilization of Patients with Multiple Myeloma: High Effectiveness and Affordable Cost

Background Autologous stem cell transplantation(ASCT) still represents an integral part of treatment for patients with eligible newly diagnosed multiple myeloma. It is important to collect enough stem cells for two transplants in the first mobilization.The combination of high-dose cyclophosphamide(Cy) (3g/m 2) plus granulocyte colony-stimulating factor(G-CSF)and on-demand plerixafor has been considered the effective method as mobilization regimen, but G-CSF requires daily, multi-injection administration. Here, we performed a real-world analysis to evaluate the efficacy and cost of high-dose Cy combination pegylated recombinant human granulocyte colony-stimulating factor（PEG-rhG-CSF）and on-demand plerixafor for the first time, allowing for a single injection given the long half-life and slow elimination of PEG-rhG-CSF. Methods We retrospectively compared 343 patients whith MM mobilized between August 2008 and December 2022 using the following mobilization strategies: Cy+PEG-rhG-CSF+/-plerixafor(n=61), Cy+PEG-rhG-CSF(n=89),Cy+ G-CSF( n=169), G-CSF+plerixafor(n=24). Then the stem cell mobilization and collection results of the four groups were compared. Results Mobilization with Cy+PEG-rhG-CSF+/-plerixafor resulted in a significantly higher total CD34+ cells ( ×10 6/kg )collected( 8.81) compared to patients mobilized with other mobilization regimens：Cy+PEG-rhG-CSF(5.47；p＜0.001),Cy+ G-CSF(4.65; p＜0.001), G-CSF+plerixafor( 2.99; p＜0.001). Day1+Day 2 CD34+ cells ( ×10 6/kg ) collected were higher in Cy+PEG-rhG-CSF+/-plerixafor group too (Cy+PEG-rhG-CSF+/-plerixafor, 7.87 vs. Cy+PEG-rhG-CSF, 4.96 vs. Cy+ G-CSF,3.92 vs. G-CSF+plerixafor, 2.43) (p＜0.001).The percentage of patients who achieved＞6×10 6/kg CD34+ cells were significantly higher in Cy+PEG-rhG-CSF+/-plerixafor group group (77.0%) than other mobilization regimens：Cy+PEG-rhG-CSF (42.7% ；p＜0.001),Cy+ G-CSF( 37.3% ;p＜0.001）, G-CSF+plerixafor( 8 % ;p＜0.001). Apheresis sessions were fewer in Cy+PEG-rhG-CSF+/-plerixafor group ( Cy+PEG-rhG-CSF+/-plerixafor, 2 vs. Cy+PEG-rhG-CSF,3 vs. Cy+ G-CSF ,3 vs. G-CSF+plerixafor,4)(p＜0.001). Patients proceeded to ASCT with a mean of 2.94 CD34+cell (×10 6/kg ) infused for PEG-rhG-CSF+/-plerixafor , 2.94 infused for Cy+PEG-rhG-CSF, 2.61infused for G-CSF+plerixafor, 3.17 infused for Cy+ G-CSF (p=0.057) . The median time to neutrophil and platelet engraftment not different in the four groups. The total cost of mobilization and apheresis using Cy+PEG-rhG-CSF+/-plerixafor was significant lower ($5670.64) compared to G-CSF+plerixafor group($11098.61), and significant higher than Cy+PEG-rhG-CSF group ($3842.23)and Cy+ G-CSF group($3727.82)（p＜0.001）. Multivariate analysis showed that patients who received Cy+PEG-rhG-CSF +/-plerixafor treatment had significantly higher likelihoods of successfully achieving the optimal harvest (6×10 6/kg) in respect to Cy+PEG-rhG-CSF group mobilized without any plerixafor. The incremental cost-effectiveness ratio, for each 1% increase in probability of achieving a successful optimal harvest, was $62.57 per patient. The incidence of neutropenic fever not different in the Cy+PEG-rhG-CSF+/-plerixafor group(4%), Cy+PEG-rhG-CSF group (10%) and Cy+ G-CSF group(18%)(p=0.051). There was no patients suffered with neutropenic fever in G-CSF+plerixafor group. Conclusion Given higher rates of successful mobilization, affordable cost and toxicity, on-demand plerixafor added to high-dose Cy and PEG-rhG-CSF may be preferable in the mobilization of patients with multiple myeloma.

Chinese expert consensus on the application of pegylated recombinant human granulocyte colony‐stimulating factor during concurrent chemoradiotherapy (2023 edition)

AbstractNeutropenia is the most common hematological toxicity of concurrent chemoradiotherapy (CCRT), and leads to subsequent treatment delays and/or dose reductions. Neutropenia often advances to febrile neutropenia and serious infections, which can affect the prognosis and safety of patients. The reasonable prevention and management of neutropenia is vital for patients with malignancies undergoing CCRT. Pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF), a long‐acting recombinant human granulocyte colony‐stimulating factor, can prevent and treat neutropenia in more convenient clinical settings. Based on relevant guidelines and the most recent clinical data, the Chinese Association for Therapeutic Radiation Oncologists, China Society for Radiation Oncology, and Chinese Association of Radiation Therapy have evaluated the safety and efficacy of PEG‐rhG‐CSF during CCRT, clearly defined the clinical pathway and route of administration for the prevention and treatment of neutropenia, and formed a Chinese expert consensus on PEG‐rhG‐CSF application during CCRT, with the goal of promoting the reasonable clinical use of this treatment.

A novel PEGylated form of granulocyte colony-stimulating factor, mecapegfilgrastim, for peripheral blood stem cell mobilization in patients with hematologic malignancies.

The Pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) has longer half-life and is given once only, which is more comfortable for patients. We aimed to evaluate the efficacy of mecapegfilgrastim for hematopoietic stem cell (HSC) mobilization in patients with hematologic malignancies and to explore the potential factors related to HSC mobilization. A retrospective analysis was performed on patients who underwent HSC mobilization in the hematology department of Mianyang Central Hospital from April 2016 to November 2022. The number of CD34 + cells collected was compared between the patients receiving mecapegfilgrastim (PEG group) and those receiving recombinant human granulocyte colony-stimulating factor (rhG-CSF group), and the possible factors for mobilization failure were analyzed. The success rates of collecting CD34 + cells in the PEG group and rhG-CSF group were 80.6% and 67.7%, respectively (χ = 1.444, P = 0.229). The median CD34 + cell counts were 3.62 × 10^6/kg and 2.92 × 10^6/kg (P = 0.178), respectively. After combination with plerixafor for mobilization, the median number of CD34 + cells collected in the PEG group and rhG-CSF group were 3.64 × 10^6/kg and 3.92 × 10^6/kg, respectively, with no significant difference (P = 0.754). There was no significant difference in hematopoietic cell recovery or infection between the groups (P > 0.05). Multivariate analysis showed that more than 5 cycles of chemotherapy (OR = 15.897, 95% CI: 1.766-143.127, P = 0.014), a precollection WBC count < 32 × 10^9/L (OR = 14.441, 95% CI: 2.180-95.657, P = 0.006) and a precollection to premobilization lymphocyte ratio < 1.7 (OR = 11.388, 95% CI: 2.129-60.915, P = 0.004) were independent risk factors for HSC mobilization failure. The HSC mobilization efficacy of mecapegfilgrastim in patients with hematologic malignancies was comparable to that of rhG-CSF, and combination with plerixafor for mobilization was feasible and effective. Patients with more than 5 cycles of chemotherapy before HSC mobilization, a precollection WBC count lower than 32 × 10^9/L, and a precollection lymphocyte count less than 1.7 times the premobilization lymphocyte count have a high probability of HSC mobilization failure.

A multicenter phase II trial of primary prophylactic PEG-rhG-CSF in pediatric patients with solid tumors and non-Hodgkin lymphoma after chemotherapy: An interim analysis.

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) can be used in pediatric patients. This study assessed the safety and efficacy of PEG-rhG-CSF as a primary prophylactic drug against neutropenia after chemotherapy in pediatric patients with solid tumors or non-Hodgkin lymphoma (NHL). This phase II study (between October 2020 and March 2022) enrolled pediatric patients with solid tumors or NHL treated with high-intensity chemotherapy and with grade ≥3 myelosuppression for at least 14 days during chemotherapy. Prophylactic PEG-rhG-CSF was given at 100 μg/kg body weight (maximum total dosage of 6 mg) once 24-48 h following chemotherapy for two cycles. The primary endpoint was the incidence of PEG-rhG-CSF-related adverse events (AEs). The key secondary endpoints were the rates of grade 3/4 neutropenia and febrile neutropenia (FN). This study included 160 pediatric patients with a median age of 6.22 (0.29, 18.00) years. Fifty-eight patients (36.25%) were diagnosed with sarcoma. AEs potentially related to PEG-rhG-CSF included bone pain (n = 32), fatigue (n = 21), pain at the injection site (n = 21), and myalgia (n = 20). The rates of grade 3/4 neutropenia and FN during treatment were 57.28% and 29.45%, respectively. PEG-rhG-CSF is well tolerated and effective in pediatric patients with solid tumors or NHL. These findings should be substantiated with further trials. ClinicalTrials.gov identifier: NCT04547829.

Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor.

We investigated the effect of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) on lymphocytes and white blood cells of patients with malignant tumors. After PEG-rhG-CSF treatment, the count of lymphocytes increased in 66 cases, remained unchanged in 2 cases, and decreased in 20 cases. The difference in lymphocyte count before and after treatment was statistically significant (P < 0.001). White blood cell changes were positively correlated with lymphocyte changes (r = 0.36, P = 0.001). In the subgroup with increased white blood cells (n = 80), there were 62 cases with increased lymphocytes, 1 case with unchanged lymphocytes, and 17 cases with decreased lymphocytes after PEG-rhG-CSF treatment. There was significant difference in the count of lymphocytes and white blood cells (P < 0.001). In the subgroup with 6 mg of PEG-rhG-CSF (n = 66) and the subgroup with 3 mg of PEG-rhG-CSF (n = 22), the changes of white blood cell and lymphocyte counts before and after treatment were statistically significant (P < 0.001). The two were positively correlated in the 6 mg PEG-rhG-CSF subgroup, with correlation coefficient r = 0.34 (P = 0.002). PEG-rhG-CSF can increase the count of lymphocytes and white blood cells in patients with malignant tumors, and the increase of lymphocytes is positively correlated with the increase of white blood cells.

Effect and safety of pegylated recombinant human G-CSF on hematopoietic reconstitution after autologous hematopoietic stem cell transplantation in lymphoma patients

Objective: Efficacy and safety analysis of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in promoting hematopoietic recovery after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with lymphoma. Methods: A total of 149 patients after auto-HSCT in Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were enrolled in this study from April 2016 to December 2021. There were 75 cases in the PEG-rhG-CSF group who were given a single subcutaneous dose of 100 µg/kg on the first day and +8 d, while 74 cases in the rhG-CSF group were given a dose of 5-10 µg·kg(-1)·d(-1) by subcutaneous injection from +1d continuing to an absolute value of neutrophil (ANC) of more than 1.5×10(9)/L. Results: ①The time of grade 3/4 agranulocytosis and neutrophil implantation in the PEG-rhG-CSF group were significantly different from that in rhG-CSF group (P=0.010, 0.030, 0.007) . There were no significant differences in the platelet implantation time, anemia incidence and duration, and platelet and red blood cell infusion within 1 month after transplantation between groups. ②The agranulocytosis with fever incidence in PEG-rhG-CSF group was similar to that in rhG-CSF group (84.0% vs 82.4% , P=0.798) , but the duration was shorter in the PEG-rhG-CSF group (4.0 d vs 5.5 d, P=0.005) . ③The incidence of infection in the PEG-rhG-CSF and the rhG-CSF groups were 22.7% (17/75) and 31.1% (23/74) , respectively (P=0.247) , and the bloodstream infection incidence were 5.3% (4/75) and 9.5% (7/74) , respectively (P=0.336) . ④The PEG-rhG-CSF group and rhG-CSF group's mean length of hospital stay were 31.5 (23-43) days and 37 (25-75) days, respectively (P<0.001) . ⑤The PEG-rhG-CSF group and rhG-CSF group's disease-free survival rates were (96.4±2.5) % and (94.7±2.6) % (P=0.638) , respectively, and the OS rates were 100.0% and (98.6±1.3) % (P=0.312) , respectively. Conclusion: PEG-rhG-CSF application after auto-HSCT in patients with lymphoma can promote hematopoietic granulocyte reconstruction and shorten hospital stay, but has no significant effect on the incidence of infection, disease-free survival, and overall survival after transplantation.

Comparison of Hematotoxicity of Pegylated Recombinant Human Granulocyte Colony-Stimulating Factor (PEG-rhG-CSF) Combined with Dual-Agent Concurrent Chemoradiotherapy and Cisplatin Concurrent Chemoradiotherapy for Locally Advanced Cervical Cancer

<h3>Purpose/Objective(s)</h3> Concurrent chemoradiotherapy (CCRT) with cisplatin is the standard treatment for locally advanced cervical cancer (LACC), but there are still some patients who have poor efficacy. Though dual-agent concurrent chemoradiotherapy (dCCRT) can improve the efficacy, the higher hematotoxicity makes it difficult to be popularized in clinical. PEG-rhG-CSF has been recommended by relevant NCCN guidelines for CCRT of malignant tumors in recent years, however there are few reports in LACC. The aim of this study was to evaluate the effect of PEG-rhG-CSF on reducing hematotoxicity in LACC with dCCRT. <h3>Materials/Methods</h3> This study retrospectively analyzed the clinical data of patients with LACC treated with CCRT in the Affiliated Cancer Hospital of Guizhou Medical University. According to patients' clinical protocol, all patients were divided into three groups, single-agent concurrent chemoradiotherapy group(sCCRT), dCCRT group and PEG-rhG-CSF combined with dCCRT group (PEG+dCCRT). Patients in sCCRT received CCRT with cisplatin 40 mg/m² for four to six cycles and patients in dCCRT were treated with paclitaxel 135-175mg/m²+cisplatin 60-80mg/m² or lobaplatin 30mg/m² for two cycles. Recombinant human granulocyte colony-stimulating factor (rhG-CSF) 5ug/kg/d was given to patients in these two groups according to the instructions. Patients in PEG+dCCRT were received dCCRT, and PEG-rhG-CSF 6mg was given in 24 to 72 hours after chemotherapy each cycle. The incidence and duration of grade 3-4 leukocytopenia and neutropenia and febrile neutropenia (FN) (according to CTCAE, V5.0) were the primary endpoints. The second endpoints were completion rate of chemotherapy and radiotherapy, time to complete radiotherapy. <h3>Results</h3> A total of 192 patients were enrolled between July 2019 and December 2021. 51 patients in sCCRT, 68 patients in dCCRT and 73 patients in PEG+dCCRT. The three groups were respectively compared for primary and second endpoints, and the results were shown below. The incidences of grade 3-4 leukocytopenia and neutropenia of the three groups (sCCRT, dCCRT and PEG+dCCRT) were 41.2%, 67.2%, 27.4% and 27.5%, 48.6%, 13.7%, respectively. The incidences of PEG+dCCRT were lowest in the three groups(P<0.05). In the three groups, the duration of grade 3-4 leukocytopenia and FN of PEG+dCCRT were observably reduced(P<0.05). There was no statistical difference of other primary and second endpoints in the three groups. <h3>Conclusion</h3> Prophylactic use of PEG-rhG-CSF during dCCRT makes hematotoxicity manageable, which may make dCCRT have better promotion and improves efficacy of LACC. However, further prospective studies are needed to confirm the results.

PEG-rhG-CSF for prophylaxis of neutropenia after chemotherapy in patients with non-small cell lung cancer: A multicenter, prospective, randomized study.

BackgroundTo evaluate the efficacy and safety of pegylated recombinant human granulocyte colony‐stimulating factor (PEG‐rhG‐CSF) in preventing neutropenia during multiple cycles of chemotherapy in patients with non–small cell lung cancer (NSCLC).MethodIn a multicenter, prospective, randomized trial, patients with NSCLC were randomly assigned in a 2:1 ratio to treatment group (PEG‐rhG‐CSF as primary prophylactic therapy) or control group. Patients in the control group were administered rhG‐CSF when white blood cell count was <2.0 × 109/L or absolute neutrophil count <1.0 × 109/L. The primary endpoint was the incidence of grade 3/4 neutropenia. Secondary endpoints included the incidence and duration of grade 3/4 neutropenia in each cycle, the incidence of febrile neutropenia (FN), delay rate of chemotherapy, prolonged time of chemotherapy, and safety.ResultsBetween January 2019 and July 2021, 130 patients were enrolled (treatment group: n = 87, control group: n = 43). The incidence of grade 3/4 neutropenia in the treatment group was significantly lower than that in the control group (1.15% vs. 11.63%, p < 0.05). The mean duration of grade 3/4 neutropenia for the treatment and control group was 2.00 and 3.75 days, respectively. There were no statistical differences in the incidence of FN, delay rate of chemotherapy, prolonged time of chemotherapy, and antibiotic use between the two groups (all p > 0.05). Adverse events were reported in 47.13% of patients in the treatment group and 48.84% patients in the control group.ConclusionsPrimary prophylactic treatment with PEG‐rhG‐CSF could reduce the incidence of neutropenia in patients with NSCLC during multiple cycles of chemotherapy, with acceptable safety and tolerability.

Anaphylaxis caused by pegylated recombinant human granulocyte colony-stimulating factor.

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF), is commonly used to prevent and/or treat neutropenia caused by tumor chemotherapy and radiotherapy with reduced clearance, increased plasma half-life, sustained biologic activity, and good safety. PEG-rhG-CSF anaphylaxis was rare. A 55-year-old male Non-Hodgkin lymphoma patient appeared with chest tightness, increased heart rate, and decreased blood pressure after taking PEG-rhG-CSF used as a primary treatment for neutropenia caused by chemoradiotherapy. The patient's anaphylaxis is likely due to PEG-rhG-CSF. 0.9% sodium chloride 250 mL and dexamethasone sodium phosphate injection 5 mg were carried out. After close observation, the symptoms were improved. Two months later, the patient was readministered with PEG-rhG-CSF and anaphylaxis reoccurred. After the last contact with PEG-rhG-CSF, the patient was prescribed rhG-CSF for many times and did not experience any adverse reactions. PEGylated drugs are not free of risk and immune-mediated adverse events are of concern. PEG is a substance capable of triggering an immune response. The mechanism of PEG involved IgE-mediated anaphylaxis and non-IgE-mediated anaphylaxis, and requires further research. PEGylated drugs are not free of risk and immune-mediated adverse events are of concern.

A randomized trial of pegylated recombinant human granulocyte-colony stimulating factor to prevent febrile neutropenia in breast cancer after chemotherapy.

e12516 Background: The purpose of this study was to evaluate the incidence of febrile neutropenia (FN) in breast cancer patients with pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) administration at 48 or 24 hours after chemotherapy for primary prevention. Methods: Patients with stage I-III invasive breast cancer who were scheduled to receive 4 cycles of adjuvant chemotherapy with EC regimen (epirubicin combined with cyclophosphamide) were eligible for this multicenter, open-label, randomized trial. Patients were randomized (1:1) to receive PEG-rhG-CSF (Jinyouli) 48 hours (48h group) or 24 hours (24h group) after the end of each cycle of chemotherapy. The primary endpoint was the incidence rate of FN. The secondary endpoints included the incidence rates of grade 3/4 neutropenia, chemotherapy dose reduction and chemotherapy delay due to neutropenia, antibiotic administration, the pain (bone, muscle, or joint), and the relative dose intensity (RDI) of the chemotherapy. Results: The preliminary results enrolled 197 patients including 96 in the 48h group and 101 in the 24h group. 78.1% of 48h group patients and 73.3% of 24h group patients completed four cycles of chemotherapy. The incidence rates of FN were 2.1% in the 48h group and 4.0% in the 24h group respectively. FN occurred in the first two cycles in the 48h group, while in the 24h group, it occurred only in the first cycles. The incidence rate of grade 3/4 neutropenia was 27.1% in the 48h group and 51.5% in the 24h group respectively. There was no delay in chemotherapy due to neutropenia in the two groups. The incidence rate of chemotherapy dose reduction due to neutropenia was 2.1% in the 48h group and 1.0% in the 24h group respectively. 2 (2.1%) patients in the 48h group and 4 (4.0%) patients in the 24h group received antibiotics. The mean RDI of each cycle of chemotherapy was 91.3% in the 48h group and 91.5% in the 24h group, respectively. The incidence rate of all grades pain (bone, muscle, or joint) was 25.0% in the 48h group, and 20.8% in the 24h group. With regard to 3 or higher grade pain, 1 (1.0%) patient in the 48h group experienced bone pain and 1 (1.0%) patient in the 24h group experienced muscle pain. Conclusions: Preliminary results suggest a similar effect of PEG-rhG-CSF administration at 48 or 24 hours after chemotherapy in primary prevention of FN in breast cancer patients receiving EC chemotherapy regimen. Recruitment is ongoing and updated data will be presented. Clinical trial information: ChiCTR1800019516. [Table: see text]

Safety and efficacy of pegylated recombinant human granulocyte colony-stimulating factor during concurrent chemoradiotherapy for small-cell lung cancer: a retrospective, cohort-controlled trial

ObjectiveTo investigate pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) safety and efficacy in preventing hematological toxicity during concurrent chemoradiotherapy (CCRT) for small-cell lung cancer (SCLC).MethodsWe retrospectively assessed 80 SCLC patients treated with CCRT from January 2013 to December 2018 who received PEG-rhG-CSF within 48 hours after the end of chemotherapy, defined as prophylactic use, as the experimental group. An additional 80 patients who were not treated with PEG-rhG-CSF were matched 1:1 by the propensity score matching method and served as the control group. The main observations were differences in hematological toxicity, neutrophil changes, febrile neutropenia (FN) incidence and adverse reactions. Progression-free survival (PFS) and overall survival (OS) were analyzed with regular assessment and follow-up.ResultsThe leukocyte, neutrophil, erythrocyte, and platelet counts and hemoglobin level decreased after CCRT, but the experimental group had slightly higher leukocyte and neutrophil counts than the control group (P < 0.05). The incidences of grade III-IV leukopenia (18.75% vs. 61.25%) and neutropenia (23.75% vs. 67.5%) in the experimental group were significantly lower than those in the control group (P < 0.05). The absolute neutrophil count was 4.17 ± 0.79 (× 109/L) on day 1 and peaked 6.81 ± 2.37 (× 109/L) on day 10 in the experimental group; the value in the control group was 2.81 ± 0.86 (× 109/L) on day 1. It decreased significantly and reached the minimum 0.91 ± 0.53 (× 109/L) on day 10 (P < 0.05). The experimental group had a lower FN incidence than the control group (P < 0.05). There was also no significant acute esophagitis or pulmonary toxicity. The treatment had no significant effect on PFS (11.4 months vs. 8.7 months, P = 0.958) or OS (23.9 months vs. 17.3 months, P = 0.325) over an 18.6-month median follow-up time.ConclusionPEG-rhG-CSF has good efficacy and safety in preventing hematological toxicity in SCLC patients during CCRT and has no significant effects on PFS or OS.

A retrospective study of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in preventing neutropenia during definitive concurrent chemoradiotherapy in patients with esophageal squamous carcinoma

ObjectiveTo compare the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) for preventive or delayed treatment in neutropenia, completion rate of concurrent chemoradiotherapy and hospitalization rate in patients with esophageal squamous carcinoma during definitive concurrent chemoradiotherapy. MethodsA total of 70 patients with esophageal squamous carcinoma in Peking University Cancer Hospital from January 2019 to December 2020, who received PEG-rhG-CSF during concurrent chemoradiotherapy, were enrolled in this retrospective analysis. There were 32 patients in the preventive group, and 38 patients in the delayed group. The incidence of neutropenia, completion rate of concurrent chemoradiotherapy and neutropenia-related hospitalization rate were compared between PEG-rhG-CSF preventive group and delayed group. ResultsThe incidence of severe neutropenia (Grades 3–4) in all patients was 31.4%. Comparison between preventive group and delayed group showed that the incidence of severe neutropenia was 6.3% and 39.4% (χ2 ​= ​10.428, P ​= ​0.001), respectively. In preventive group, the incidence of severe neutropenia was 3.7% and 20.0%, respectively, for primary prevention and secondary prevention of PEG-rhG-CSF (χ2 ​= ​12.321, P ​= ​0.001). The completion rate of concurrent chemoradiotherapy was 93.8% in the preventive group and 63.2% in the delayed group (χ2 ​= ​9.220, P ​= ​0.002). The incidence of treatment interruption was 25.7% in the whole group, 12.5% in the preventive group and 36.8% in the delayed group (χ2 ​= ​5.389, P ​= ​0.020). Seven patients (7/70, 10.0%) were hospitalized and treated with intravenous antibiotics for neutropenia, including 1 in the preventive group and 6 in the delayed group (P ​= ​0.078). ConclusionsProphylactic use of PEG-rhG-CSF during concurrent chemoradiotherapy for patients with esophageal squamous carcinoma can effectively reduce the incidence of neutropenia, ensure the safety of treatment, and improve the completion rate of concurrent chemoradiotherapy.

Prophylactic administration of mecapegfilgrastim after chemotherapy in patients with lymphoma.

Neutropenia is a common and serious complication encountered during chemotherapy treatment of cancer patients. The incidence of neutropenia increases the risk of infection and can influence the chemotherapy treatment in terms of drug dosage and treatment duration. Mecapegfilgrastim is a novel, long-acting pegylated recombinant human granulocyte-colony stimulating factor (PEG-rhG-CSF) designed to prevent the incidence of neutropenia. The study aims to observe the effectiveness and safety of mecapegfilgrastim as prophylaxis for chemotherapy-induced neutropenia in patients with lymphoma. Ninety-one patients with lymphoma were enrolled and received mecapegfilgrastim as either primary or secondary prophylaxis. The incidence of grade III/IV neutropenia, the duration of grade III/IV neutropenia in the overall population, and the differences between the primary and secondary prophylaxis groups were investigated. Adverse events were also recorded. During the first chemotherapy cycle, the incidence of grade III and grade IV neutropenia was 5% and 7%, respectively. Of the 71 patients who received mecapegfilgrastim as primary prophylaxis, the incidence of grade III and grade IV neutropenia was 4% and 1%, respectively. Of the 20 patients who received mecapegfilgrastim as secondary prophylaxis, the incidence of grade III and grade IV neutropenia was 10% and 25%, respectively. The mean duration of grade III neutropenia was 0.85 days. The mean duration of grade III neutropenia in patients who received mecapegfilgrastim as primary prophylaxis was one day less than patients who received mecapegfilgrastim as secondary prophylaxis. Fever and bone/muscle pain were the most frequently observed adverse events. Mecapegfilgrastim is more effective in reducing the incidence of grade III/IV neutropenia and the mean duration of febrile neutropenia (FN) when used as primary prophylaxis rather than secondary prophylaxis in patients with lymphoma. The toxicity of mecapegfilgrastim was tolerable.

667 PEGYLATED RECOMBINANT HUMAN GRANULOCYTE COLONY STIMULATING FACTOR IN DEFINITIVE CHEMORADIOTHERAPY OF ESOPHAGEAL CANCER: PRELIMINARY RESULTS

Abstract To compare the efficiency and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF), on the risk of neutropenia in patients with esophageal squamous cell carcinoma (ESCC) of definitive chemoradiotherapy (dCRT). Methods ESCC patients receiving dCRT in our hospital were adopted in this study. Patients in the PEG-rhG-CSF group were treated with preventive PEG-rhG-CSF 6 mg subcutaneously at 24–48 h after completion of chemotherapy of each cycle, while the control group was not. The usage of rhG-CSF was permitted when the absolute neutrophil count (ANC) ≤2 × 109/L, or white blood cell count (WBC) ≤3 × 109/L. Results A total of 34 ESCC patients were in the PEG-rhG-CSF group and 41 were in the control group. Improved chemotherapy cycle completion and radiation dose completion were identified in the PEG-rhG-CSF group (P &amp;lt; 0.001). Leukocyte recovery and neutrophil recovery, (P &amp;lt; 0.001). PEG-rhG-CSF reduced incidence of neutropenia, and time to ANC recovery in different chemotherapy cycles, with (Cycle 1–2, P &amp;lt; 0.001 ~ P = 0.02) or without RT (Cycle 3–4, P = 0.04 ~ P = 0.8799). Antibiotics utilization rates were significantly higher in the PEG-rhG-CSF group during concurrent chemotherapy with RT, but not during consolidative CRT (Cycle 3 and Cycle 4: P &amp;gt; 0.05). Conclusion PEG-rhG-CSF prescribed as prophylaxis reduces acute toxicities by concurrent CRT and contributes to completion of dCRT regime in locally advanced ESCC therapeutics. The significance was not observed in chemotherapy alone without RT in the current findings.

Clinical efficacy and safety of mecapegfilgrastim in small cell lung cancer as primary prophylaxis of neutropenia post chemotherapy: a retrospective analysis.

Neutropenia is the most common adverse reaction seen in small cell lung cancer after chemotherapy. Febrile neutropenia (FN) leads to an increase in hospitalizations and may even be life-threatening. This paper aims to investigate the efficacy and adverse reactions of mecapegfilgrastim in the primary prophylaxis of neutropenia in patients with small cell lung cancer after receiving intermediate risk chemotherapy with at least one patient risk factor. The clinical records of 106 patients with small cell lung cancer admitted to Zhejiang Cancer Hospital from June 2019 to January 2021 were retrospectively analyzed. Patients were divided into a mecapegfilgrastim [pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF)] group and control group, each with 53 patients. The mecapegfilgrastim group received subcutaneous injection of mecapegfilgrastim 24 hours after the first cycle of chemotherapy, while the control group did not receive this. The Chi-square (χ2) test or Fisher exact test were used to compare the incidence of neutropenia, FN, and the proportion of patients administrated with full dose chemotherapy in the two groups after the first cycle of chemotherapy. Data on adverse events after mecapegfilgrastim were also collected. After the first cycle of chemotherapy, the incidence of neutropenia in the mecapegfilgrastim group was significantly lower than that in the control group (P=0.001) and the incidence of FN in the mecapegfilgrastim group was lower than that in the control group (P=0.118). The proportion of patients administrated with full-dose chemotherapy in the mecapegfilgrastim group was significantly higher than that in the control group (P=0.001). The main adverse reactions to mecapegfilgrastim were muscle pain, fever, and fatigue. After receiving intermediate risk chemotherapy, the incidence of neutropenia was significantly reduced by the primary prophylaxis of mecapegfilgrastim in patients with small cell lung cancer. The adverse events of mecapegfilgrastim were mild and tolerable, and included muscle pain, fever, and fatigue.

A clinical study of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during concurrent chemoradiotherapy of cervical cancer

PurposeTo evaluate the effectiveness and safety of pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) in preventing neutropenia during chemoradiotherapy in patients with cervical cancer.MethodsFrom August 2018 to April 2020, 60 patients who were pathologically confirmed as cervical cancer were randomly divided into two groups at a ratio of 2:1: PEG-modified-rhG-CSF experimental group and control group. The primary endpoints were the incidence of grade 3–4 neutropenia. Secondary endpoints included the duration of grade 3–4 neutropenia, the incidence of grade 4 neutropenia, the incidence of febrile neutropenia (FN), delay rate of chemotherapy, prolonged time of chemotherapy, time to complete radiotherapy and safety.ResultsThe incidence of grade 3–4 neutropenia in the experimental group was significantly lower than the control group (10% vs. 77.78%, P < 0.001). However, there was no statistical significance between the two groups in the duration of grade 3–4 neutropenia (3.75 days vs. 5.07 days, P = 0.871). The experimental group was better than the control group in the incidence of grade 4 neutropenia, the incidence of FN and delay rate of chemotherapy, and the difference was statistically significant (P < 0.05). Besides, the prolonged time of chemotherapy and the time to complete radiotherapy in the experimental group were less than those in the control group, but the difference was not statistically significant (P > 0.05). The incidence of adverse events in the experimental group and control group were 55.00 and 94.44%, respectively, and the difference was statistically significant (P = 0.003).ConclusionPEG-rhG-CSF preventive treatment used in the course of chemoradiotherapy for patients with cervical cancer can reduce the incidence of neutropenia and improve the incidence of delayed chemotherapy cycles.Trial registrationClinicalTrials.gov, NCT04542356. Registered 9 September 2020 - Retrospectively registered.

Efficacy and Safety of PEG-rhG-CSF in HSC Mobilization in 71 Normal Healthy Donors for Allogeneic Hematopoietic Stem Cell Transplantation

To retrospectively analyze the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF) in hematopoietic stem cell mobilization in 71 normal healthy donors for allogeneic hematopoietic stem cell transplantation (allo-HSCT). From March 2018 to July 2019, 71 patients received allo-HSCT in The General Hospital of Western Theater Command were enrolled in the study, a single dose of PEG-rhG-CSF was injected subcutaneously at 12 mg to all the stem cell donors. After injection for 4 days, CD34+ cell number were detected, stem cells were collected on day 4 or 5 according to the CD34+ cell number. The successful collection criteria were CD34+ cells≥2×106/kg, and the excellent collection criteria were CD34+ cells≥4×106/kg. The side effects after mobilization were observed and the collection time, the success rate, excellent rate, and times of the collection were evaluated in the donors, as well as the infused cell number, the engraftment rate, the time of engraftment, and the incidence of acute graft-versus-host disease (aGVHD) of the recipients. Seventy-one healthy stem cell donors included 39 males and 32 females with a median age of 38 (16-58) years old. The median number of CD34+ cells on day 4 was 46 (7.4-133)/μl, of which 39 cases with CD34+ cells ≥ 40/μl were collected on day 4, 28 cases with CD34+ cells 20-40/μl were collected on day 5, and 4 cases with CD34+ cells <20/μl were collected on day 5 after a salvage treatment with rhG-CSF. Sixty-five cases were collected once, while 6 cases twice. The median number of collected CD34+ cells was 6.1(3.1-18.1)×106/kg. The success collection rate was 100% (71/71), and the excellent collection rate was 81.6% (58/71). All the cases had varying degrees of muscle and bone soreness, 17 cases (23.9%) had headache, 11 cases (15.5%) had fatigue, and 3 cases (4.2%) had a mild fever. Among 71 recipients, the median number of infused mononuclear cells (MNC) was 8.3(5-23.3)×108/kg, the median number of infused CD34+ cells and CD3+ cells was 5.3(3.1-10.7)×106/kg and 1.9 (0.5-7.6)×108/kg, respectively. Among them, 68 cases (95.8%) had a stable engraftment, the median time of neutrophil engraftment was 11(8-19) days, and the median time of platelet engraftment was 12(8-23) days. Among the 68 cases who were engrafted, 15 cases (22%) had grade Ⅱ-Ⅳ aGVHD, including grade Ⅲ-Ⅳ aGVHD in 3 patients (4.4%), 2 cases (2.9%) died of severe aGVHD. For allo-HSCT donor mobilization, PEG-rh-G-CSF is effective, safe, and convenient, providing more options for HSC mobilization.