Effectiveness and safety of primary prophylaxis with G-CSF after induction therapy for acute myeloid leukemia: a systematic review and meta-analysis of the clinical practice guidelines for the use of G-CSF 2022 from the Japan society of clinical oncology.

Although granulocyte colony-stimulating factor (G-CSF) reduces the incidence, duration, and severity of neutropenia, its prophylactic use for acute myeloid leukemia (AML) remains controversial due to a theoretically increased risk of relapse. The present study investigated the effects of G-CSF as primary prophylaxis for AML with remission induction therapy. A detailed literature search for related studies was performed using PubMed, Ichushi-Web, and the Cochrane Library. Data were independently extracted and assessed by two reviewers. A qualitative analysis of pooled data was conducted, and the risk ratio with corresponding confidence intervals was calculated in the meta-analysis and summarized. Sixteen studies were included in the qualitative analysis, nine of which were examined in the meta-analysis. Although G-CSF significantly shortened the duration of neutropenia, primary prophylaxis with G-CSF did not correlate with infection-related mortality. Moreover, primary prophylaxis with G-CSF did not affect disease progression/recurrence, overall survival, or adverse events, such as musculoskeletal pain. However, evidence to support or discourage the use of G-CSF as primary prophylaxis for adult AML patients with induction therapy remains limited. Therefore, the use of G-CSF as primary prophylaxis can be considered for adult AML patients with remission induction therapy who are at a high risk of infectious complications.

Effect of Pneumocystis jirovecii pneumonia prophylaxis on hematologic toxicity in patients receiving chemoradiation for primary brain tumors.

PURPOSE: Diffuse gliomas are managed with radiation and temozolomide; however, this therapy often results in hematologic toxicities. Patients undergoing chemoradiation also risk contracting Pneumocystis jirovecii pneumonia (PJP), and frequently receive prophylaxis against PJP during treatment. Independent of chemoradiation, some PJP prophylaxis drugs have the potential to cause myelosuppression, which could require cessation of chemotherapy. Here, we evaluate differences in the frequency of hematologic toxicities during chemoradiation when patients receive PJP prophylaxis. METHODS: This retrospective chart review evaluated patients with primary brain tumors treated with radiation and concurrent temozolomide. Analyses were performed to assess the effect of the type of PJP prophylaxis on risk for neutropenia, lymphopenia, or thrombocytopenia and the severity of these adverse effects as defined using the Common Terminology Criteria for Adverse Events. RESULTS: Of the 217 patients included in this analysis, 144 received trimethoprim-sulfamethoxazole (TMP/SMX) and 69 received pentamidine. Of the patients who received TMP/SMX, 15.3% developed an absolute neutrophil count < 1500 cells/µL compared with 7.2% of patients receiving pentamidine (p = 0.10). Platelet count < 100,000/µL occurred in 18.1% of patients who received TMP/SMX and 20.3% of patients who received pentamidine (p = 0.70). No significant differences in lymphocyte counts between therapies were seen. Severity of hematologic toxicities were similar between PJP prophylaxis groups. CONCLUSION: These findings suggest that the type of PJP prophylaxis does not significantly affect the risk for hematologic toxicity in brain tumor patients receiving radiation and temozolomide. Additional studies are merited to evaluate the higher rate of neutropenia in patients on TMP/SMX observed in this study.

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

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Cost-effectiveness analysis of mecapegfilgrastim and recombinant human granulocyte stimulating factor for primary prophylaxis of chemotherapy-induced neutropenia in non-small cell lung cancer.

OBJECTIVE: To evaluate the efficacy, safety, and economics of mecapegfilgrastim and recombinant human granulocyte colony-stimulating factor (rhG-CSF) in the primary prevention of chemotherapy-related neutropenia in non-small cell lung cancer (NSCLC). MATERIALS AND METHODS: Data from 181 patients with NSCLC who received intermediate risk chemotherapy were collected from the information system of a tertiary hospital in China. Patients were categorized into two groups: those treated with mecapegfilgrastim (n = 91) and those treated with rhG-CSF (n = 90). The clinical efficacy rates of neutropenia prevention were used as effect indicators, and a cost-effectiveness analysis was conducted from the perspective of the Chinese healthcare system. Logistic regression, generalized linear regression, and bootstrap methods were used for sensitivity analyses. RESULTS: There was no statistical difference between the mecapegfilgrastim and rhG-CSF groups in clinical efficacy rates (98.9 vs. 97.8%). However, the total cost in the mecapegfilgrastim group was significantly higher than that in the rhG-CSF group (16,341.6 CNY vs. 14,371.1 CNY, p = 0.03). The cost-minimization analysis shows that mecapegfilgrastim is not cost-effective. The sensitivity analyses confirm that these results are robust. CONCLUSION: Compared with rhG-CSF, mecapegfilgrastim is not a cost-effective strategy for NSCLC patients in neutropenia prevention in China.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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 7 days 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. CONCLUSION: 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.

Efficacy and safety of pegfilgrastim biosimilar MD-110 in patients with breast cancer receiving chemotherapy: Single-arm phase III.

INTRODUCTION: Pegfilgrastim is indicated to decrease the incidence of chemotherapy-induced febrile neutropenia. It is the first granulocyte-colony stimulating factor approved for prophylactic use regardless of carcinoma type and is marketed in Japan as G-LASTA (Kyowa Kirin Co., Ltd., Tokyo, Japan). MD-110 is a biosimilar of pegfilgrastim. This phase III, multicenter, open-label, single-arm study investigated the efficacy and safety of MD-110 in early-stage breast cancer patients receiving neoadjuvant or adjuvant myelosuppressive chemotherapy. METHODS: A total of 101 patients received the study drug. Each patient received docetaxel 75 mg/m2 and cyclophosphamide 600 mg/m2 (TC) for four cycles on day 1 of each cycle. MD-110 (3.6 mg) was administered subcutaneously on day 2 of each cycle. The primary efficacy endpoint was the duration of severe neutropenia during cycle 1 (days with absolute neutrophil count < 500/mm3 ). The safety endpoints were adverse events and the presence of antidrug antibodies. RESULTS: The mean (SD) duration of severe neutropenia for MD-110 was 0.2 (0.4) days. The upper limit of the two-sided 95% confidence interval for the mean duration of severe neutropenia was 0.2 days, below the predefined threshold of 3.0 days. The incidence of febrile neutropenia, the secondary efficacy endpoint, was 6.9% (7/101). Adverse events, occurring in more than 50% of patients, were alopecia, constipation, and malaise, which are common side effects of TC chemotherapy. Antidrug antibodies were negative in all patients. CONCLUSION: MD-110 was effective against chemotherapy-induced neutropenia. No additional safety concern, compared with the originator, was observed in patients with breast cancer receiving TC chemotherapy.(JapicCTI-205230).

Semimechanistic pharmacokinetic-pharmacodynamic model of tripegfilgrastim for pediatric patients after chemotherapy.

Tripegfilgrastim is a long-acting granulocyte colony-stimulating factor (G-CSF) that has been used to prevent chemotherapy-induced neutropenia in adults. This study aimed to establish a pharmacokinetic (PK)-pharmacodynamic (PD) model to explore the impact of chemotherapy and tripegfilgrastim on absolute neutrophil counts (ANCs) and to further propose a fixed-dose regimen in pediatric patients. Because neutrophils affect the clearance of tripegfilgrastim, the semimechanistic PK-PD model was developed simultaneously by using data from 40 healthy adults and 27 pediatric patients with solid tumors. Tripegfilgrastim PK and ANC dynamics were described with a pharmacodynamics-mediated drug disposition model assuming quasi-equilibrium with five transit compartments mimicking neutrophil granulopoiesis. The effect of chemotherapy on neutrophils was included by stimulating the elimination of the G-CSF receptor at the mitotic cells. Healthy adult and pediatric patients showed significantly different value for dissociation constant of the tripegfilgrastim-G-CSF receptor complex (Kd ) and apparent volume of distribution (Vd /F). Patients treated with chemotherapy had a higher Vd /F and 62% lower Kd than healthy adults. As the age increased, the absorption rate of tripegfilgrastim was decreased. Body weight affected the G-CSF receptor-mediated internalization of tripegfilgrastim, and the baseline ANC value impacted the production rate of G-CSF receptors. Simulations from the developed model suggested that 1.5, 2.5, 4, and 6 mg single subcutaneous tripegfilgrastim doses for the respective weight groups of 10-20, 21-30, 31-44, and more than 45 kg significantly reduced the duration of Grade 4 neutropenia similar to tripegfilgrastim weight-based treatment with 100 µg/kg.

Efficacy and safety of PEG-rhG-CSF versus rhG-CSF in preventing chemotherapy-induced-neutropenia in early-stage breast cancer patients.

BACKGROUND: To compare the clinical value of recombinant human granulocyte colony-stimulating factor (rhG-CSF) and pegylated rhG-CSF(PEG-rhG-CSF) in early-stage breast cancer (EBC) patients receiving adjuvant chemotherapy, compare the efficacy of PEG-rhG-CSF with different dose and explore the timing of rhG-CSF rescue treatment. METHODS: Patients in two PEG-rhG-CSF subgroups were given 3 mg or 6 mg PEG-rhG-CSF within 24 ~ 48 h after chemotherapy for preventing myelosuppression, while patients in the rhG-CSF group were given rhG-CSF. Observation indicators include the incidence of febrile neutropenia (FN) and grade 3/4 chemotherapy-induced-neutropenia (CIN), the overall levels and nadir values of white blood cells (WBC) and absolute neutrophil count (ANC), comparison of WBC and ANC curves over time, the incidence of CIN-related complications, the incidence of adverse events in each group and the timing of rescue treatment for rhG-CSF. RESULTS: There was no significant difference in the incidence of FN in the first cycle among the groups (P = 0.203). But the incidence of ≥ 3 grade CIN in two PEG-rhG-CSF subgroups was significantly lower than that in the rhG-CSF group (P < 0.001). The overall WBC and ANC levels in the PEG-rhG-CSF group were significantly higher than those in the rhG-CSF group (P < 0.001). In terms of CIN-related complications, less chemotherapy delay rate (1.1 vs. 7.5%, P = 0.092), less dose reduction rate (6.9 vs. 7.5%, P = 1.000), less antibiotic use rate (3.4 vs. 17.5%, P = 0.011) and less proportion of rhG-CSF rescue therapy (24.1 vs. 85.0%, P < 0.001) in the PEG-rhG-CSF group, and there were no significant differences between PEG-rhG-CSF subgroups. In the incidence of adverse events among the groups, there were no statistical differences. All patients undergoing rhG-CSF rescue treatment were mainly 4 grade (63.6%) and 3 grade (25.5%) CIN, and 10.9% of patients with 1 ~ 2 grade CIN who had high infection risk or had been infected. CONCLUSION: PEG-rhG-CSF has better efficacy and equal tolerance compared with rhG-CSF in preventing CIN in EBC patients receiving EC regimen. Moreover, a half-dose 3 mg PEG-rhG-CSF also had good efficacy. Last, patients with ≥ 3 grade CIN and others who have been assessed to be at high risk of infection or have co-infection should consider rhG-CSF or even antibiotic rescue treatment.

[Consensus on clinical diagnosis, treatment, and prevention of chemotherapy-induced neutropenia in China (2023 edition)].

Chemotherapy-induced neutropenia (CIN) is a common hematological adverse events and dose-limiting toxicities of chemotherapy. CIN may lead to dose reduction and delay of chemotherapeutic agents, febrile neutropenia and severe infection, which results in increased treatment cost, reduced efficacy of chemotherapy, and even life-threatening morbidities. Assessment of risk of CIN, early detection of FN and infection, and proper prevention and treatment play a crucial role in reducing the occurrence of CIN-related morbidities, improving patient treatment safety and anticancer efficacy. Based on evidence and expert opinion, the expert committee of Chinese Anti-Cancer Association issued "the consensus on diagnosis and treatment of chemotherapy-induced neutropenia in China (2023 edition)", which is an update version of the 2019 edition, aiming to provide reference for the diagnosis and treatment of CIN for Chinese oncologists.

Comparison of prophylactic effects for chemotherapy induced neutropenia between same-day versus next-day administration of pegteograstim (Neurapeg®) in patients treated with chemotherapy regimen composed of day 1 intensive myleosuppressive agent: A randomized phase III clinical trial.

BACKGROUND AND PURPOSE: Administration of pegylated granulocyte-colony-stimulating factor (peg-GCSF) 24 to 72 hours after chemotherapy is usually recommended. Next-day administration (after 24 hours) resulted in fewer duration of grade (Gr) 4 chemotherapy-induced neutropenia (CIN) and decreased severity of CIN than same-day (within 4 hours). However, patients sometimes receive same-day Peg-GCSF for the sake of convenience. In addition, a few prior studies showed that the same-day method is comparable or superior to the next-day method in preventing CIN, especially in chemotherapy regimens that include day 1 myelosuppressive agents. Thus, we aim to verify the hypothesis that same-day administration of pegteograstim, a new formulation of peg-GCSF, is non-inferior to next-day administration in terms of Gr4 CIN duration. METHODS: This study is a randomized, multicenter, open-label, investigator-initiated phase 3 study. Patients with adjuvant/neoadjuvant or first-line palliative chemotherapy comprising intensively myelosuppressive agents on day 1 (mFOLFIRINOX, ECb, EP, FOLFIRI, and FOLFOX) are enrolled. The patients are assigned to the same-day arm or the next-day arm in a 1:1 ratio. The randomizations are stratified according to number of patient CIN risk factors (1 vs ≥2), chemotherapy setting (perioperative vs palliative), and interval (2-week vs 3-week). In the same-day arm, pegteograstim 6 mg is subcutaneously injected within 4 hours after completion of chemotherapy. In the next-day arm, pegetograstim is injected at 24 to 36 hours post-chemotherapy. A complete blood count test is performed daily from day 5 to 9 during the cycle 1. The primary endpoint is duration of Gr4 CIN (cycle 1), and secondary endpoints include incidence of Gr 3 to 4 CIN (cycle 1), severity of CIN (cycle 1), time to recovery absolute neutrophil count 1000/µL (cycle 1), incidence of febrile neutropenia, incidence of CIN-related dose delay, and dose intensity. In order to verify non-inferiority of 0.6 days, we estimated a significance level of 5%, power of 80%, and drop-out rate of 15%. This results in the need for a total of 160 patients, 80 in each group.

G-CSF rescue of FOLFIRINOX-induced neutropenia leads to systemic immune suppression in mice and humans.

BACKGROUND: Recombinant granulocyte colony-stimulating factor (G-CSF) is routinely administered for prophylaxis or treatment of chemotherapy-induced neutropenia. Chronic myelopoiesis and granulopoiesis in patients with cancer has been shown to induce immature monocytes and neutrophils that contribute to both systemic and local immunosuppression in the tumor microenvironment. The effect of recombinant G-CSF (pegfilgrastim or filgrastim) on the production of myeloid-derived suppressive cells is unknown. Here we examined patients with pancreatic cancer, a disease known to induce myeloid-derived suppressor cells (MDSCs), and for which pegfilgrastim is routinely administered concurrently with FOLFIRINOX but not with gemcitabine-based chemotherapy regimens. METHODS: Serial blood was collected from patients with pancreatic ductal adenocarcinoma newly starting on FOLFIRINOX or gemcitabine/n(ab)paclitaxel combination chemotherapy regimens. Neutrophil and monocyte frequencies were determined by flow cytometry from whole blood and peripheral blood mononuclear cell fractions. Serum cytokines were evaluated pretreatment and on-treatment. Patient serum was used in vitro to differentiate healthy donor monocytes to MDSCs as measured by downregulation of major histocompatibility complex II (HLA-DR) and the ability to suppress T-cell proliferation in vitro. C57BL/6 female mice with pancreatic tumors were treated with FOLFIRINOX with or without recombinant G-CSF to directly assess the role of G-CSF on induction of immunosuppressive neutrophils. RESULTS: Patients receiving FOLFIRINOX with pegfilgrastim had increased serum G-CSF that correlated with an induction of granulocytic MDSCs. This increase was not observed in patients receiving gemcitabine/n(ab)paclitaxel without pegfilgrastim. Interleukin-18 also significantly increased in serum on FOLFIRINOX treatment. Patient serum could induce MDSCs as determined by in vitro functional assays, and this suppressive effect increased with on-treatment serum. Induction of MDSCs in vitro could be recapitulated by addition of recombinant G-CSF to healthy serum, indicating that G-CSF is sufficient for MDSC differentiation. In mice, neutrophils isolated from spleen of G-CSF-treated mice were significantly more capable of suppressing T-cell proliferation. CONCLUSIONS: Pegfilgrastim use contributes to immune suppression in both humans and mice with pancreatic cancer. These results suggest that use of recombinant G-CSF as supportive care, while critically important for mitigating neutropenia, may complicate efforts to induce antitumor immunity.

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.

BACKGROUND: 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). PATIENTS AND METHODS: 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). RESULTS: 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. CONCLUSION: PEG-rhG-CSF is well tolerated and effective in pediatric patients with solid tumors or NHL. These findings should be substantiated with further trials. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04547829.

Randomized Phase II Cabazitaxel Dose Individualization and Neutropenia Prevention Trial in Patients with Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: There is ongoing controversy about the recommended dose of cabazitaxel in patients with metastatic castration-resistant prostate cancer (mCRPC). PATIENTS AND METHODS: This multicenter phase II open-label, randomized, parallel-group study compared 3-weekly cabazitaxel at 25 mg/m2 (conventional arm A) with cabazitaxel therapeutic drug monitoring (experimental arm B) in mCRPC. The primary objective was to improve the clinical feasibility rate (CFR), defined as the absence of grade 4 neutropenia or thrombocytopenia, any thrombocytopenia with bleeding, febrile neutropenia, severe nonhematologic toxicity, withdrawal for cabazitaxel-related toxicity, or death. A total of 60 patients had to be randomized to detect a difference in CFR of 35% (power 80%, two-sided alpha 10%). RESULTS: A total of 40 patients were randomized to arm A and 33 patients to arm B. CFR was 69.4% in arm A and 64.3% in arm B (P = 0.79). Week-12 PSA response was 38.5% in both arms. A radiological response by RECIST v.1.1 was seen in 3 (9.7%) patients in arm A versus 6 (23.1%) patients in arm B (P = 0.28), disease progression was higher in arm A compared with arm B (61.3% vs. 30.8%, P = 0.05). Median progression-free survival was longer in arm B compared with arm A (9.5 vs. 4.4 months; HR = 0.46; P = 0.005). Median overall survival was higher in arm B compared with arm A (16.2 vs. 7.3 months; HR = 0.33; P < 0.0001). CONCLUSIONS: Pharmacokinetic-guided dosing of cabazitaxel in patients with mCRPC is feasible and improves clinical outcome due to individual dose escalations in 55% of patients.

Outcome and Cost-Effectiveness Analysis of Long-acting G-CSF as Primary Prophylaxis of Neutropenia Induced by Chemotherapy in Breast Cancer Patients, From a Retrospective Study.

PURPOSE: This retrospective analysis aimed to evaluate the clinical outcomes and cost-effectiveness of long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia caused by chemotherapy for breast cancer. METHODS: Patients with breast cancer who received long- or short-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia were enrolled in this study, and incidences of neutropenia were compared between two groups. A decision-analytic and a Markov model were used to compare the health benefits and costs of utilizing long- vs short-acting granulocyte-colony stimulating factor as the primary prophylaxis from the perspective of the Chinese health service system. Subsequently, one-way deterministic and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratios were calculated in baseline and sensitivity analyses. RESULTS: Patients receiving long-acting granulocyte-colony stimulating factor as the primary prophylaxis of chemotherapy-induced neutropenia experienced a significant lower incidence of this adverse event, compared with the short-acting one for 2 to 7 days. The outcomes of baseline analysis indicated that long-acting granulocyte-colony stimulating factor had a gain of 0.08 quality-adjusted life years and costed $149 more than the short-acting one, yielding an incremental cost-effectiveness ratio of $1792 per quality-adjusted life year. The sensitivity analysis proved the stability of our models and economic efficiency of long-acting granulocyte-colony stimulating factor. CONCLUSIONS: Patients receiving long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia experienced lower risk of this event compared with those underusing short-acting one. The long-acting granulocyte-colony stimulating factor may be a more cost-effective strategy for primary prophylaxis of neutropenia than short-acting one, considering the Chinese willingness-to-pay threshold of $12158.6 per quality-adjusted life year.

Impact of Granulocyte Colony-Stimulating Factor (G-CSF) on the Outcomes of Patients With Metastatic Pancreatic Adenocarcinoma (MPA) During First-Line Treatment With FOLFIRINOX: A Single-Center Retrospective Analysis.

INTRODUCTION: The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with metastatic pancreatic adenocarcinoma (MPA) treated with FOLFIRINOX is unknown. We aimed to compare the frequencies of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) and survival outcomes according to the use of PP. METHODS: This is a retrospective study. We included patients with pathologically confirmed MPA treated with FOLFIRINOX in first-line. Patients who received primary prophylaxis (PP group) were compared to patients who received secondary or no G-CSF (no-PP group). Overall survival (OS) and progression-free survival (PFS) were evaluated using the standard Cox proportional hazard model. To account for potential biases, we performed sensitivity analyses excluding patients who received secondary prophilaxis and treating G-CSF as a time-dependent covariate in extended Cox proportional hazard models. RESULTS: The study population consisted of 123 patients. PP was used by 75 patients (61.0%). G3/4 N occurred more frequently among patients without PP (10.7 vs 41.7%; P < .001). There was no difference in the frequency of FN between groups (5.3 vs 8.3%; P = .710). In multivariate analysis, PP was associated with a trend toward improved OS (HR = .66; 95% confidence interval [95% CI] .41 - 1.07; P = .094). In the multivariate model excluding patients with secondary prophylaxis (HR = .54; 95% CI 0.32 - .91; P = .022) and in the time-dependent model (HR = .47; 95% CI 0.28 - .80; P = .005), PP was associated with statistically superior OS. CONCLUSIONS: Despite the reduction in the frequency of G3/4N, the risk of FN among patients treated with FOLFIRINOX without G-CSF is too low to justify its use in a routine basis. However, given the potential of G-CSF to improve survival in this setting, further studies are warranted to assess its role during treatment with FOLFIRINOX for patients with MPA.

Consensus on clinical diagnosis, treatment, and prevention of chemotherapy-induced neutropenia in China (2023 edition) / 中华肿瘤杂志

Chemotherapy-induced neutropenia (CIN) is a common hematological adverse events and dose-limiting toxicities of chemotherapy. CIN may lead to dose reduction and delay of chemotherapeutic agents, febrile neutropenia and severe infection, which results in increased treatment cost, reduced efficacy of chemotherapy, and even life-threatening morbidities. Assessment of risk of CIN, early detection of FN and infection, and proper prevention and treatment play a crucial role in reducing the occurrence of CIN-related morbidities, improving patient treatment safety and anticancer efficacy. Based on evidence and expert opinion, the expert committee of Chinese Anti-Cancer Association issued "the consensus on diagnosis and treatment of chemotherapy-induced neutropenia in China (2023 edition)", which is an update version of the 2019 edition, aiming to provide reference for the diagnosis and treatment of CIN for Chinese oncologists.

Effect of granulocyte colony-stimulating factor on toxicities after CAR T cell therapy for lymphoma and myeloma.

Chimeric antigen receptor T cells (CAR T) are groundbreaking therapies but may cause significant toxicities including cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and cytopenias. Granulocyte colony-stimulating factor (G-CSF) is often used to mitigate neutropenia after CAR T, but there is no consensus recommended strategy due to hypothesized, but largely unknown risks of exacerbating toxicities. To investigate the impact of G-CSF, we retrospectively analyzed 197 patients treated with anti-CD19 CAR T for lymphoma and 47 patients treated with anti-BCMA CAR T for multiple myeloma. In lymphoma, 140 patients (71%) received prophylactic G-CSF before CAR T (mostly pegylated G-CSF) and were compared with 57 patients (29%) treated with G-CSF after CAR T or not exposed. Prophylactic G-CSF was associated with faster neutrophil recovery (3 vs. 4 days, P < 0.01) but did not reduce recurrent neutropenia later. Prophylactic G-CSF was associated with increased grade ≥2 CRS (HR 2.15, 95% CI 1.11-4.18, P = 0.02), but not ICANS. In multiple myeloma, prophylactic G-CSF was not used; patients were stratified by early G-CSF exposure (≤2 days vs. ≥3 days after CAR T or no exposure), with no significant difference in toxicities. Future trials should clarify the optimal G-CSF strategy to improve outcomes after CAR T.

Prophylaxis of chemotherapy-induced neutropenia with lipegfilgrastim in patients with lung cancer: final results from the non-interventional study NADIR.

OBJECTIVE: Real-world evidence on the application of the granulocyte colony-stimulating factor lipegfilgrastim for the reduction of chemotherapy-induced neutropenia and febrile neutropenia (FN) is limited. The NADIR study aimed to evaluate effectiveness and safety of lipegfilgrastim as primary or secondary prophylaxis in patients with lung cancer undergoing chemotherapy in routine clinical practice. METHODS: The non-interventional study NADIR (German Clinical Trials Register (DRKS) Number DRKS00005711) enrolled 156 patients with small-cell lung cancer (SCLC) and 145 patients with non-small-cell lung cancer (NSCLC), who received lipegfilgrastim during chemotherapy. Primary endpoint was the incidence of severe neutropenia (CTCAE grade 3/4) and FN. The analysis was stratified for age groups (≤65 years vs. >65 years). RESULTS: Approximately half of the patients were aged >65 years (SCLC 54.5%; NSCLC 46.9%). Intention of antineoplastic treatment was mostly palliative (SCLC 89.1%; NSCLC 73.1%). Patients with high FN risk (SCLC 44.9%; NSCLC 28.3%) mostly received lipegfilgrastim for primary prophylaxis (SCLC 81.4%; NSCLC 70.7%). FN was reported in 1.9% SCLC and 1.4% NSCLC patients. At least one severe neutropenia was documented in 30.1% SCLC and 17.9% NSCLC patients. For NSCLC patients aged >65 years, less severe neutropenia was reported as compared to younger patients (14.7% vs. 20.8%). Lipegfilgrastim-related adverse events were reported in 10.3% SCLC and 7.7% NSCLC patients. CONCLUSION: Lipegfilgrastim in routine clinical practice of patients with lung cancer showed similar effectiveness and safety as compared to the pivotal trial. Interestingly, in older patients severe neutropenia was reported less frequently. While most patients with high FN risk received lipegfilgrastim for primary prophylaxis as recommended, there are still 20-30% of patients at high FN risk without primary prophylaxis who could benefit from better adherence to guidelines.