Use Of Granulocyte Colony-stimulating Factor Research Articles

Alternative therapy for lymphoma with febrile neutropenia using traditional Chinese medicine: A case report

IntroductionFebrile neutropenia is a common complication in patients undergoing chemotherapy for hematologic malignancies and is associated with significant morbidity and mortality. Primary granulocyte colony-stimulating factor (G-CSF) prophylaxis is consistently associated with a notable reduction in the risk of febrile neutropenia. However, the use of G-CSF in patients who are already neutropenic from chemotherapy remains controversial. Studies have shown that 12.9% of cancer patients incorporate traditional Chinese medicine (TCM) to alleviate chemotherapy side effects in Taiwan; thereby providing an alternative management strategy for neutropenic fever in cancer patients. Case presentationThis is an 18-year-old female with newly diagnosed precursor T-lymphoblastic lymphoma. After chemotherapy, the patient developed febrile neutropenia. Despite the use of antibiotics and G-CSF, the febrile neutropenia persisted for two months. Approximately ten days after the initiation of traditional Chinese medicine decoction with the strategy of tonifying the spleen and stomach, clearing yin fire, and uplifting yang, her absolute neutrophil count (ANC) had gradually increased. Additionally, after two weeks of treatment, her fever subsided. The patient continued with chemotherapy and was discharged in stable condition. DiscussionAntibiotic use aligns with the TCM perspective of an “attack” approach. Conversely, our TCM decoction was designed to raise the ANC by tonifying the spleen and stomach, clearing Yin Fire, and uplifting Yang. Li Dongyuan, one of the four great masters of the Jin Yuan Dynasty, created the formula: Bupiwei Shengyang Sanhuo Decoction that is notable in this regard. The herbs in our decoction have shown hematopoietic and myelosuppression-alleviating effect. For many patients who do not respond adequately to G-CSF alone, integrative treatments involving both TCM and Western medicine can offer additional therapeutic benefits by increasing blood cell counts.

Impact of Neutropenia on Clinical Outcomes after Lung Transplantation.

Neutropenia is a frequent complication among solid organ transplant (SOT) recipients receiving immunosuppressive therapy and antimicrobial prophylaxis. However, there are limited studies analysing the frequency and impact of neutropenia in lung transplant recipients (LTRs). Our aim was to analyse the frequency of neutropenia, the need for granulocyte colony-stimulating factor (GCSF) treatment within the first 18 months post-transplant and its association with acute rejection, chronic lung allograft dysfunction (CLAD), overall survival and the development of infections. This observational and retrospective study recruited 305 patients who underwent lung transplantation between 2009 and 2019, with outpatient quarterly follow-up during the first 18 months post-surgery. During this period, 51.8% of patients experienced at least one episode of neutropenia. Neutropenia was classified as mild in 50.57% of cases, moderate in 36.88% and severe in 12.54%. GCSF treatment was indicated in 23.28% of patients, with a mean dose of 3.53 units. No statistically significant association was observed between neutropenia or its severity and the development of acute rejection, CLAD or overall survival. However, the patients who received GCSF treatment had a higher mortality rate compared to those who did not. Sixteen patients (5.25%) developed infections during neutropenia, with bacterial infections being the most common. Neutropenia is common in the first 18 months after lung transplantation and most episodes are mild. We did not find an association between neutropenia and acute rejection, CLAD, or mortality. However, the use of GCSF were associated with worse post-transplant survival.

Association of Granulocyte Colony-Stimulating Factor Treatment with Risk of Brain Metastasis in Advanced Stage Breast Cancer.

The routine use of granulocyte colony-stimulating factor (GCSF) is not recommended for the prevention or treatment of chemotherapy-induced neutropenia or febrile neutropenia because risks associated with certain types of cancers, distant organ metastases, and primary tumor growth cannot be excluded. We examined the association between GCSF use and the incidence of brain metastasis (BM), as well as BM-free survival (BMFS). This retrospective cohort study included 121 stage IV breast cancer patients without confirmed BM at the time of diagnosis and who received at least one course of systematic chemotherapy or target therapy at a tertiary teaching hospital between 1 January 2014 and 31 December 2022. The effect of GCSF use on BM was assessed with other confounding factors in Cox regression analyses. In this retrospective cohort, patients who received GCSF treatment had a significantly higher incidence of BM than those who did not (34.9% vs. 13.8%, p = 0.011). Univariate Cox regression analysis showed that GCSF use, menopause status, hormone treatment, HER2 treatment, cumulative dosage, dosage density, and neutropenia were independent risk factors for BMFS (p < 0.05). GCSF users had a higher risk of BM (adjusted HR: 2.538; 95% CI: 1.127-5.716, p = 0.025) than nonusers. BM risk was significantly associated with those with neutropenia (RR: 1.84, 95% CI: 1.21, 2.80) but not with those without neutropenia (RR: 0.59, 95% CI: 0.41-0.84, Interaction p-value < 0.05). The higher the dose density of GCSF, the higher the risk compared with those who do not use GCSF (p for trend < 0.01). These preliminary results suggest that GCSF is associated with BM in patients with stage IV breast cancer who did not have BM at initial diagnosis. Further comprehensively designed large-scale observational studies are needed to confirm our preliminary results.

7245 A case of refractory methimazole-induced agranulocytosis treated with high-dose G-CSF

Abstract Disclosure: S. Shah: None. D. Mathur: None. G. Bao: None. S. Shah: None. D.M. Antoniucci: None. Case Presentation: Despite their efficacy in treating hyperthyroidism, antithyroid drugs (ATDs) carry a rare risk of life-threatening agranulocytosis (ANC &amp;lt;500/μL), with incidence varying from 0.1 to 0.4%. Patients with agranulocytosis may benefit from granulocyte-colony stimulating factor (G-CSF) to shorten recovery and reduce hospitalization costs. We present the case of a 37-year-old woman with Graves disease, who developed methimazole (MMZ)-induced agranulocytosis and was treated with high-dose G-CSF. At diagnosis, MMZ 10 mg BID was started and later reduced to 5 mg BID. After 2 months, she presented to the ED with a dental infection, an arm abscess after a cat scratch, and fevers. Blood-work showed WBC of 1500/μL, ANC of 0/μL, and rare granulocytes on manual differential. Flow cytometry did not show clonal lymphoid or blast populations. MMZ was stopped and antibiotics were started. Her hyperthyroidism was managed with propranolol and iodine solution in anticipation of definitive thyroidectomy. On day 4 of admission, tbo-filgrastim 450 mcg daily injections were started for persistent neutropenia. Despite 3 doses of G-CSF, ANC remained at 0/μL, prompting a bone marrow biopsy that showed no dysplastic or aplastic phenotype. After 9 doses of G-CSF up to 600 mcg daily, ANC fully recovered on day 14. She underwent thyroidectomy, and 2 months later her ANC and thyroid hormone levels were within normal. Discussion: This report illustrates a case of severe, refractory ATD-induced agranulocytosis and highlights the utility of G-CSF in treating high risk patients. Classically, ATD-induced agranulocytosis occurs in those aged &amp;gt;65 years, follows high dose therapy, and occurs within 60 days of treatment initiation. G-CSF is often used in clinical practice, although its efficacy is not well established. A recent meta-analysis demonstrated that G-CSF can hasten recovery by 3 days. Other studies report no difference or prolonged agranulocytosis up to 14 days despite G-CSF, especially in patients with ANC &amp;lt;100/μL. Whether this is a lack of true benefit or inadequate dosing is unclear. This case reviews the use of high dose G-CSF in a patient with profound neutropenia. Prompt ANC recovery was crucial given neutropenic fevers and need for thyroidectomy. Even with escalating doses of G-CSF, her ANC required 14 days to recover - twice the typical length of recovery. Whether G-CSF impacted the time course of her recovery is difficult to discern. Identifying the mechanisms underlying ATD induced agranulocytosis may explain delayed responses to G-CSF. Notably, the 2016 ATA guidelines do not incorporate G-CSF into ATD-induced agranulocytosis management. This conservative approach reflects a paucity of evidence supporting G-CSF use. Further research must investigate underlying mechanisms and clarify indications for G-CSF use to improve outcomes and reduce costs of care. Presentation: 6/1/2024

Early Recognition of Drug-Induced Febrile Neutropenia Leads to an Improved Outcome in the Trauma Intensive Care Unit: A Case Report

AbstractTraumatic brain injury necessitates the use of antiepileptics for seizure prophylaxis, which are associated with multiple side effects including neutropenia, which may be dose dependent or idiosyncratic. We report the case of a young male with traumatic brain injury who developed febrile neutropenia, likely secondary to antiepileptic use. Early recognition and stopping of the drugs with use of granulocyte colony-stimulating factor led to the successful management of the patient.

Trends in the use of granulocyte colony stimulating factors for older patients with cancer, 2010 to 2019

IntroductionOlder patients with cancer receiving myelosuppressive treatment are at an increased risk for developing febrile neutropenia (FN) or having chemotherapy dose-reductions or delays, resulting in suboptimal health outcomes. Granulocyte colony stimulating factors (G-CSF) are effective medications to reduce these adverse events and are recommended for patients ≥65 years receiving chemotherapy with >10 % FN risk. We sought to characterize the trends and predictors of G-CSF use between the youngest-old (66–74 years), middle-old (75–84 years), and oldest-old (≥85 years) patients with cancer. Materials and MethodsWe used registry data from SEER-Medicare for breast, lung, ovarian, colorectal, esophageal, gastric, uterine, prostate, pancreatic cancer, and non-Hodgkin lymphoma (NHL) diagnoses from 2010 to 2019. Cox proportional hazard analysis was used. ResultsOverall, 41.4 % of patients received G-CSF from chemotherapy initiation to three days after completion of the first chemotherapy course. The use rate remained relatively stable for all cancers, except for an increase in use for those with pancreatic cancer. G-CSF use decreased as patients got older. The oldest-old were 43.0 % (95 % confidence interval: 40.7–45.2 %) less likely to receive G-CSF compared to the youngest-old. Patients with breast cancer or NHL were more likely to receive G-CSF than those with other cancers. Patients who were female, married, White or Hispanic, and had fewer comorbidities were more likely to receive G-CSF. DiscussionG-CSF is used less often in populations at higher risk of developing FN and related complications. Improving adherence to recommendations can improve health outcomes, especially in the oldest adults, older males, and Black patients.

Development of VLA4 and CXCR4 Antagonists for the Mobilization of Hematopoietic Stem and Progenitor Cells.

The treatment of patients diagnosed with hematologic malignancies typically includes hematopoietic stem cell transplantation (HSCT) as part of a therapeutic standard of care. The primary graft source of hematopoietic stem and progenitor cells (HSPCs) for HSCT is mobilized from the bone marrow into the peripheral blood of allogeneic donors or patients. More recently, these mobilized HSPCs have also been the source for gene editing strategies to treat diseases such as sickle-cell anemia. For a HSCT to be successful, it requires the infusion of a sufficient number of HSPCs that are capable of adequate homing to the bone marrow niche and the subsequent regeneration of stable trilineage hematopoiesis in a timely manner. Granulocyte-colony-stimulating factor (G-CSF) is currently the most frequently used agent for HSPC mobilization. However, it requires five or more daily infusions to produce an adequate number of HSPCs and the use of G-CSF alone often results in suboptimal stem cell yields in a significant number of patients. Furthermore, there are several undesirable side effects associated with G-CSF, and it is contraindicated for use in sickle-cell anemia patients, where it has been linked to serious vaso-occlusive and thrombotic events. The chemokine receptor CXCR4 and the cell surface integrin α4β1 (very late antigen 4 (VLA4)) are both involved in the homing and retention of HSPCs within the bone marrow microenvironment. Preclinical and/or clinical studies have shown that targeted disruption of the interaction of the CXCR4 or VLA4 receptors with their endogenous ligands within the bone marrow niche results in the rapid and reversible mobilization of HSPCs into the peripheral circulation and is synergistic when combined with G-CSF. In this review, we discuss the roles CXCR4 and VLA4 play in bone marrow homing and retention and will summarize more recent development of small-molecule CXCR4 and VLA4 inhibitors that, when combined, can synergistically improve the magnitude, quality and convenience of HSPC mobilization for stem cell transplantation and ex vivo gene therapy after the administration of just a single dose. This optimized regimen has the potential to afford a superior alternative to G-CSF for HSPC mobilization.

Efficacy and Safety of Bendamustine-Rituximab as Frontline Therapy for Indolent Non-Hodgkin Lymphoma: A Real-World, Single-Center, Retrospective Study.

Background The use of bendamustine with an anti-CD20 monoclonal antibody as frontline therapy for indolent non-Hodgkin lymphoma(NHL)has become a standard of care.We aimed to evaluate the real-world efficacy and safety of bendamustine-rituximab (BR) frontline therapy for indolent NHL. Patients and methods Patients with indolent NHL treated with frontline BR therapy in Hôpital du Sacré-Coeur de Montréal, from January 2015 to August 2018 were included in this retrospective study. Results Our cohort included 42 adults with a median age of 63 years. Follicular lymphoma was the most common histology (n = 31, 74%). Most patients had advanced disease (Lugano stage III or IV, 88%). The overall response rate was 84% (complete response = 62% and partial response = 22%). Median progression-free survival (PFS) was not reached. At 30 months, PFS was 74.8% and overall survival was 90%. Grade 3-4 neutropenia occurred in 21% of patients. Infection-related adverse events were observed in 17 patients (40%). Most were grade 1 and 2 events (84%).One case of grade 5 progressive multifocal leukoencephalopathy related to John Cunningham (JC) virus reactivation was observed. The most common non-infectious-related adverse events were mild nausea and fatigue. Conclusions The efficacy and safety of BR treatment for indolent NHL were comparable in our real-life cohort compared to prior studies. This supports BR as a standard of care for indolent NHL. Future studies should assess whether the use of granulocyte-colony stimulating factors as primary prophylaxis effectively mitigates the hematological and infection-related adverse events related to BR therapy.

Subcutaneous G-CSF administration improves IVF outcomes in patients with recurrent implantation failure presenting a KIR/HLA-C mismatch

Research questionDespite advances in assisted reproductive technologies, many blastocysts are lost unexpectedly during implantation. Alterations in maternal immune tolerance towards fetal antigens may contribute to adverse IVF outcomes. The purpose of this study is to evaluate whether administering Granulocyte Colony-Stimulating Factor (G-CSF) to couples with a Human Leukocyte Antigen/Killer-Cell Immunoglobulin-Like Receptor (HLA/KIR) mismatch could positively modulate the implantation process in patients with recurrent implantation failure (RIF). A KIR/HLA-C mismatch occurs when the interaction between KIRs and HLA-C causes an inhibition of NK cells, which may result in reduced G-CSF secretion leading to impaired placentation and increased risk of miscarriage, pre-eclampsia and fetal growth restriction. DesignA retrospective monocentric cohort study conducted at the IVI Clinic in Rome, including women with a history of at least two failed blastocyst transfers. Couples underwent KIR and HLA-C testing. Couples with a KIR/HLA-C mismatch received G-CSF subcutaneously up to week nine of gestation. The mismatch included cases with inhibitory KIR genotypes and HLA-C2C2 females with HLA-C1C1, or C1C2 males or HLA-C1C2 females with male HLA-C2C2. The reproductive outcomes were assessed, and the logistic regression models controlled for potential confounders affecting IVF outcomes. Results79 patients with RIF and a KIR/HLA-C mismatch were included in the study. 30 patients were administered G-CSF, and 49 received no treatment. In the univariate analysis, no statistically significant differences were reported in the reproductive outcomes after IVF between the women treated with G-CSF and the control group. However, the logistic regression analysis that controlled for confounding factors showed that patients treated with subcutaneous G-CSF had statistically significant higher ongoing-pregnancy (aOR=3.808) and live-birth (aOR=4.998) rates, and a lower miscarriage rate (aOR=0.057). No statistically significant differences were found in other reproductive outcomes. ConclusionThe use of subcutaneous G-CSF in patients with a KIR/HLA-C mismatch undergoing IVF may reduce miscarriage and improve live-birth rates. G-CSF may modulate NK-mediated immune mechanisms and improve trophoblast invasion and development. Randomized trials are warranted to validate these findings and enhance the chances of successful pregnancies in couples with an immunological mismatch.

Real-world use patterns, effectiveness, and tolerability of sacituzumab govitecan for second-line and later-line treatment of metastatic triple-negative breast cancer in the United States

PurposePatients with metastatic triple-negative breast cancer (mTNBC) have poor prognosis and limited treatment options. Sacituzumab govitecan (SG), a Trop-2–directed antibody–drug conjugate, is approved for patients with mTNBC who have received ≥ 2 systemic therapies (≥ 1 in the metastatic setting) based on the ASCENT study (NCT02574455). The current study describes real-world SG use and outcomes in patients with mTNBC in the United States.MethodsThis retrospective, observational study included adult patients with mTNBC from the ConcertAI Patient360™ database who received SG in the second line (2L) and later from April 2020 to May 2022. SG use patterns, effectiveness, and tolerability are described.ResultsThis analysis included 230 patients (median age 60 years, 26% Black, 17% with ECOG performance status ≥ 2, 66% in community settings; median of 2 prior lines of treatment in the metastatic setting); median follow-up was 7.2 months. Median (95% CI) real-world overall survival was 10.0 (8.3–11.1) months for all patients and 13.9 (9.8-not estimable) months in the 2L subgroup (n = 77). Granulocyte-colony stimulating factor (G-CSF) was administered concomitantly with SG in 134 (58%) patients; 35 (15%) received G-CSF for the first time. Median (IQR) time from SG start to G-CSF use was 8.5 (8.0–29.0) days. Seventeen (7%) patients discontinued SG due to toxicity.ConclusionsUsing a real-world, ethnically diverse population of patients with mTNBC presenting with poor prognosis, these data reinforced the findings from ASCENT. In routine clinical practice, SG is an effective treatment in the 2L setting, consistent with treatment guidelines.

Effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for invasive breast cancer: a systematic review and meta-analysis from Clinical Practice Guidelines for the Use of G-CSF 2022.

Chemotherapy for breast cancer can cause neutropenia, increasing the risk of febrile neutropenia (FN) and serious infections. The use of granulocyte colony-stimulating factors (G-CSF) as primary prophylaxis has been explored to mitigate these risks. To evaluate the efficacy and safety of primary G-CSF prophylaxis in patients with invasive breast cancer undergoing chemotherapy. A systematic literature review was conducted according to the "Minds Handbook for Clinical Practice Guideline Development" using PubMed, Ichushi-Web, and the Cochrane Library databases. Randomized controlled trials (RCTs) and cohort studies assessing using G-CSF as primary prophylaxis in invasive breast cancer were included. The primary outcomes were overall survival (OS) and FN incidence. Meta-analyses were performed for outcomes with sufficient data. Eight RCTs were included in the qualitative analysis, and five RCTs were meta-analyzed for FN incidence. The meta-analysis showed a significant reduction in FN incidence with primary G-CSF prophylaxis (risk difference [RD] = 0.22, 95% CI: 0.01-0.43, p = 0.04). Evidence for improvement in OS with G-CSF was inconclusive. Four RCTs suggested a tendency for increased pain with G-CSF, but statistical significance was not reported. Primary prophylactic use of G-CSF is strongly recommended for breast cancer patients undergoing chemotherapy, as it has been shown to reduce the incidence of FN. While the impact on OS is unclear, the benefits of reducing FN are considered to outweigh the potential harm of increased pain.

Primary prophylaxis with G-CSF for patients with non-round cell soft tissue sarcomas: a systematic review for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.

Granulocyte colony-stimulating factor (G-CSF) is an essential supportive agent for chemotherapy-induced severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for non-round cell soft tissue sarcoma (NRC-STS)?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve NRC-STS treatment outcomes?" for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology. A literature search was performed on the primary prophylactic use of G-CSF for NRC-STSs. Two reviewers assessed the extracted papers and analyzed overall survival, incidence of febrile neutropenia, infection-related mortality, quality of life, and pain. Eighty-one and 154 articles were extracted from the literature search for CQs #1 and #2, respectively. After the first and second screening, one and two articles were included in the final evaluation, respectively. Only some studies have addressed these two clinical questions through a literature review. The clinical questions were converted to future research questions because of insufficient available data. The statements were proposed: "The benefit of primary G-CSF prophylaxis is not clear in NRC-STS" and "The benefit of intensified chemotherapy with primary G-CSF prophylaxis is not clear in NRC-STSs." G-CSF is often administered as primary prophylaxis when chemotherapy with severe myelosuppression is administered. However, its effectiveness and safety are yet to be scientifically proven.

A simplified G-CSF–free procedure allows for in vivo HSC gene therapy of sickle cell disease in a mouse model

AbstractWe have reported the direct repair of the sickle cell mutation in vivo in a disease model using vectorized prime editors after hematopoietic stem cell (HSC) mobilization with granulocyte colony-stimulating factor (G-CSF)/AMD3100. The use of G-CSF for HSC mobilization is a hurdle for the clinical translation of this approach. Here, we tested a G-CSF-free mobilization regimen using WU-106, an inhibitor of integrin α4β1, plus AMD3100 for in vivo HSC prime editing in sickle cell disease (SCD) mice. Mobilization with WU-106 + AMD3100 in SCD mice was rapid and efficient. In contrast to the G-CSF/AMD3100 approach, mobilization of activated granulocytes and elevation of the key proinflammatory cytokine interleukin-6 in the serum were minimal. The combination of WU-106 + AMD3100 mobilization and IV injection of the prime editing vector together with in vivo selection resulted in ∼23% correction of the SCD mutation in the bone marrow and peripheral blood cells of SCD mice. The treated mice demonstrated phenotypic correction, as reflected by normalized blood parameters and spleen size. Editing frequencies were significantly increased (29%) in secondary recipients, indicating the preferential mobilization/transduction of long-term repopulating HSCs. Using this approach, we found <1% undesired insertions/deletions and no detectable off-target editing at the top-scored potential sites. Our study shows that in vivo transduction to treat SCD can now be done within 2 hours involving only simple IV injections with a good safety profile. The same-day mobilization regimen makes in vivo HSC gene therapy more attractive for resource-poor settings, where SCD does the most damage.

Patient characteristics associated with primary prophylactic granulocyte colony-stimulating factor (G-CSF) use among women treated for early-stage breast cancer.

e12605 Background: The National Comprehensive Cancer Network (NCCN) recommends several chemotherapy regimens for early-stage breast cancer that have elevated risk of neutropenia (&gt;20%). In these regimens, primary prophylactic use of granulocyte colony-stimulating factor (G-CSF) is recommended. Little is known about how patient-level factors relate to receipt of prophylactic G-CSF among women receiving these regimens. Methods: In the Optimal Breast Cancer Chemotherapy Dosing (OBCD) Study, we examined use of G-CSF among women with stage I-IIIA breast cancer between 2005-2019 in Kaiser Permanente Northern California (KPNC) and Kaiser Permanente Washington (KPWA). We evaluated the patient-level factors associated with primary prophylactic G-CSF use (≤7 days before to ≤3 days after first day of chemotherapy) among women receiving chemotherapy regimens with high risk of neutropenia, for which the NCCN guidelines recommend prophylactic G-CSF use. Multivariable-adjusted prevalence ratios (PR) and their corresponding 95% Confidence Intervals (95% CI) were calculated using generalized linear models of the Poisson family with a log link-function and robust standard errors. Results: Overall, while all 3,083 women receiving these regimens ultimately received G-CSF, 2412 (79%) received primary prophylactic G-CSF within the period 7 days prior to 3 days post first cycle. Younger women had higher prevalence of prophylactic G-CSF receipt (82.7% in ages 18-39 years vs. 58.1% in 70+ years). Black women had higher prevalence of receipt compared to white women (82.7% in non-Hispanic Black women vs 76.1% in White women). Women with a higher body mass index (BMI) had lower prevalence of receipt compared to normal weight women (73.3% in 35+ kg/m2 group vs 81.5% in 18.5-&lt;25 kg/m2 group). In multivariable models, older women were less likely to receive prophylactic G-CSF (PR70+ vs 18-39: 0.69; 95% CI: 0.57-0.84; p-trend&lt;0.001), as were those with a higher BMI (PRBMI 35+ vs 18.5-&lt;25: 0.92; 95% CI: 0.85, 0.97; p-trend=0.006), and a later year of diagnosis (PR2016-19 vs 2005-07: 0.81; 95% CI: 0.77, 0.85; p-trend&lt;0.001). Although race/ethnicity was not significantly associated with receipt of prophylactic G-CSF use overall in multivariable models, we observed Non-Hispanic Black women to experience slightly higher likelihood of G-CSF receipt than Non-Hispanic White women (PR: 1.08; 95% CI: 1.02, 1.15). Conclusions: Women of older age and those with higher BMI were less likely to receive primary prophylactic G-CSF, as were women treated in later years. Further research looking at timing of G-CSF use is warranted, as are studies examining provider/facility-level factors in relation to patterns of G-CSF use, G-CSF’s impact on survival outcomes, and the real-world impact of decisions around G-CSF use across age, BMI, and racial/ethnic groups.

Cost-effectiveness analysis of later-line treatments for refractory metastatic colorectal cancer.

3525 Background: Recent clinical trials support regorafenib dose optimization (ReDO), a combination therapy with trifluridine/tipiracil and bevacizumab (TAS-BEV), and fruquintinib (FRUQ) for the treatment of refractory metastatic colorectal cancer (mCRC). This study evaluated relative cost-effectiveness of ReDO, TAS-BEV, and FRUQ for mCRC from a payer perspective in the United States. Methods: A Markov model was constructed to estimate total costs and quality-adjusted life years (QALY) for each treatment. In the base case, clinical parameters were obtained from the ReDOS study for ReDO, the SUNLIGHT study for TAS-BEV, and the FRESCO study for FRUQ. Economic parameters were obtained from IBM Micromedex RED BOOK for treatment costs and from the Centers for Medicare &amp; Medicaid Services and the Agency for Healthcare Research and Quality for health care resource use. Incremental cost-effectiveness ratio (ICER) was used to evaluate relative cost-effectiveness of treatments. Model robustness was checked with deterministic (DSA) and probabilistic sensitivity analysis (PSA). A subgroup analysis was performed in patients with and without previous use of anti-VEGF therapy, but using the FRESCO-2 study for FRUQ because OS and PFS for this subgroup was unavailable in the FRESCO study. Results: In the base case, ReDO provided a higher QALY at a lower cost than TAS-BEV and FRUQ. During the first two months following treatment initiation, TAS-BEV had a higher total cost ($67,862) than ReDO ($44,695) and FRUQ ($48,688), partly due to the cost of managing neutropenia and using concomitant granulocyte colony stimulating factors (GCSF). The base case results were robust in DSA and PSA. Most influential parameters determining relative cost-effectiveness were related to treatment cost and effectiveness. In patients with previous anti-VEGF therapy, ReDO provided a higher QALY at a lower cost (0.571 QALY; $86,694) than TAS-BEV (0.490 QALY; $148,784) and FRUQ (0.411 QALY; $101,236). In patients without previous anti-VEGF therapy, TAS-BEV had a higher QALY (0.755 vs 0.571) and a higher cost ($232,701 vs $86,694) than ReDO, resulting in an ICER of $790,988 per QALY. Conclusions: ReDO was cost-effective compared with TAS-BEV and FRUQ, regardless of previous use of anti-VEGF therapy. In the base case, ReDO had a lower treatment cost than TAS-BEV and FRUQ, especially during the first month of dose optimization. TAS-BEV had the highest total cost, partly due to the cost of managing neutropenia and GCSF use. [Table: see text]

Adverse events in real-world patients (pts) with metastatic pancreatic ductal adenocarcinoma (mPDAC) who received FOLFIRINOX (FFX) or gemcitabine with nab-paclitaxel (GnP) in the first line (1L).

e16321 Background: FFX and GnP are the most common 1L treatments for mPDAC. Each regimen is associated with a different profile of toxic effects that impact quality of life. However, the regimens have not been directly compared for safety or efficacy in a randomized controlled trial. RW studies of the frequency of adverse events (AEs) under each regimen have reported inconsistent results. Supportive care such as granulocyte colony-stimulating factor (G-CSF) also affects the rate of hematologic AEs. We assessed AEs and G-CSF use in a RW cohort of mPDAC pts treated with FFX or GnP in the 1L. Methods: This retrospective observational study utilized the Ontada Clinical Data View: Pancreatic Cancer database. Adult pts diagnosed with mPDAC between November 2018 and November 2022 who initiated treatment with 1L FFX or GnP within 90 days of their diagnosis for metastatic disease were included in the study. Diarrhea, fatigue, nausea and vomiting, and neuropathy were available in the data as ungraded AEs abstracted from clinician notes. Assessment of hematologic and hepatic AEs were based on observed lab values and were graded according to the Common Terminology Criteria for AEs version 5. Results: 2,918 pts met study inclusion criteria: 1,703 received 1L GnP and 1,215 received 1L FFX. For the GnP vs. FFX cohorts, the median age at 1L initiation was 71yr (IQR: 64–76) vs. 65yr (IQR: 58–71), 52% vs. 57% were male, 65% vs. 68% were white, 9% vs. 15% had an ECOG score of 0, and 40% vs. 39% had an ECOG score of 1. GnP pts had a statistically significantly greater rate of grade 1/2 and 3/4 neutropenia (26% vs. 15%, p = .001; 25% vs. 17%, p = .014), grade 1/2 thrombocytopenia (25% vs. 20%, p &lt; .001), grade 1/2 and 3/4 anemia (87% vs. 68%, p &lt; .001; 19% vs. 6%, p = .001), grade 1/2 elevated ALT (62% vs. 44%, p &lt; .001), grade 1/2 elevated AST (68% vs. 50%, p &lt; .001), and grade 1/2 elevated ALP (68% vs. 58%, p &lt; .001). For GnP vs. FFX, there was no statistically significant difference in grade 3/4 thrombocytopenia (9% vs. 5%, p &lt; .001), grade 3/4 elevated ALT (6% vs. 5%, p = .367), grade 3/4 elevated AST (9% vs. 5%, p = .170), grade 3/4 elevated ALP (11% vs. 11%, p = .417), and grade 1/2 and 3/4 hypokalemia (32% vs. 34%, p = .241; 7% vs. 13%, p = .060). There were not statistically significant differences for GnP vs. FFX for AEs reported in clinician notes including diarrhea (12% vs. 18%, p = .074), fatigue (15% vs. 12%, p = .187), nausea and vomiting (10% vs. 11%, p = .399), and neuropathy (15% vs. 12%, p = .219). G-CSF was used by 19% vs. 57% of GnP vs. FFX patients (p &lt; .001), with median time to first use of G-CSF 14 days (IQR: 7–35) vs. 0 days (IQR: 0–14). Conclusions: In a RW cohort of mPDAC pts treated with 1L GnP or FFX, pts experienced a variety of serious AEs. The burden of AEs was higher among the RW GnP cohort than the RW FFX cohort. G-CSF was more prevalent and began earlier in the FFX cohort, indicating prophylactic use.

Safety in the use of granulocyte-colony stimulating factor during concurrent chemotherapy and thoracic radiotherapy in patients with small-cell lung cancer: A meta-analysis.

Safety in the use of granulocyte-colony stimulating factor during concurrent chemotherapy and thoracic radiotherapy in patients with small-cell lung cancer: A meta-analysis.

Efficacy and safety of mecapegfilgrastim in preventing neutropenia during concurrent chemoradiotherapy.

e24119 Background: Current guidelines recommend prophylactic use of granulocyte colony-stimulating factor (G-CSF) to reduce the incidence, duration, and severity of chemotherapy-induced neutropenia. We evaluated the efficacy and safety of mecapegfilgrastim, a long-acting G-CSF, in preventing neutropenia for solid tumor patients during concurrent chemoradiotherapy (CCRT). Methods: In this multicenter, open-label, randomized controlled trial, patients with lung, esophageal, or cervical cancers, and an ECOG performance status of 0-2 were randomized 1:1 to the study or control group. Both groups received standard CCRT with two 21-day cycles of taxanes and platinum-based chemotherapy. In the study group, mecapegfilgrastim 6 mg was administered 24 hours after chemotherapy for each cycle, whereas the control group received no prophylaxis for neutropenia. Short-acting G-CSF was administered if neutrophil counts fell below 2.0×10^9/L. Treatment-emergent adverse events (TEAEs) were monitored for 2 cycles and graded per CTCAE v5.0. The primary endpoint was the incidence of grade 3/4 neutropenia during CCRT. Results: From Apr 2022 to Dec 2023, 97 patients were enrolled: 48 in the study group and 49 in the control group. The median age was 59 years (range 51-71) in the study group and 60 years (range 34-71) in the control group. Baseline characteristics were balanced between two groups. Eleven patients (22.9%) in the study group experienced grade 3/4 neutropenia, compared to 27 (55.1%) in the control group (nominal p= 0.002). Three patients (6.3%) in the study group and 2 (4.1%) in the control group developed febrile neutropenia (FN). For 18 lung cancer patients, none of the study group experienced grade 3/4 neutropenia, while 2 patients (25.0%) in the control group did. FN was not reported in either group. Among 40 esophageal cancer patients , grade 3/4 neutropenia was observed in 4 patients (21.1%) of the study group, compared to 12 (57.1%) of the control group, with one case of FN in each group. For 39 gynecological cancer patients, grade 3/4 neutropenia occurred in 7 patients (36.8%) in the study group and 13 (65.0%) in the control group. Two patients of the study group and 1 of the control group developed FN. Short-acting G-CSF was required in 18 patients (37.5%) of the study group and 33 (67.4%) of the control group. TEAEs were reported in 27 patients (56.3%) of the study group and 41 (83.7%) of the control group. Notably, grade ≥3 TEAEs were reported in 21 patients (43.8%) of the study group and 30 (61.2%) of the control group, maily including hematologic toxicities like neutropenia, thrombocytopenia, and lymphocytopenia. Serious TEAEs were reported in 1 patient (2.1%) of the study group and 2 (4.1%) of the control group. One patient (2.1%) in the study group discontinued treatment due to TEAEs. Conclusions: Prophylaxis with mecapegfilgrastim reduced the incidence of grade 3/4 neutropenia during CCRT, with good safety. Clinical trial information: ChiCTR2200058551.

Trilaciclib use for prevention of hematological adverse events in chemotherapy: A meta-analysis of real-world studies and clinical trials.

e24130 Background: Trilaciclib, a cyclin-dependent kinase (CDK)-4 and -6 inhibitor, is the only FDA-approved agent that preemptively protects hematopoietic stem cells from chemotherapy-induced myelosuppression (CIM) without compromising efficacy. It transiently arrests hematopoietic stem cells in the G1 phase, thus temporarily blocking progression through the cell cycle and protecting progenitor cells from cytotoxicity. It has been approved for use in extensive-stage small-cell lung cancer (SCLC). Limited real-world evidence of its efficacy exists owing to its recent approval. We sought to enhance our understanding and evaluate the preventive effect of trilaciclib through a combined meta-analysis of clinical trials and retrospective studies. Methods: A systematic literature search was performed on PubMed, Embase, Cochrane, and Scopus from inception until December 2023. Retrospective cohort studies and randomized-controlled trials with trilaciclib and non-trilaciclib arms were included. The primary outcomes of interest were CIM-related grade ≥3 hematological adverse events, and secondary outcomes included supportive care interventions to remedy CIM. Quantitative meta-analyses were conducted using the random-effects model on STATA v17. Results: The meta-analysis comprised seven studies, including four clinical trials and three real-world retrospective studies, including 6537 patients with extensive SCLC or locally recurrent or metastatic breast cancer. Chemotherapy regimens in SCLC patients included the combination of etoposide/platinum (E/P), E/P/PD-L1 inhibitors, or topotecan, and gemcitabine/carboplatin in patients with breast cancer. The mean age of the patients was 63.28 ± 5.31 years, and 49.21% were males. Administration of trilaciclib led to a reduction in the incidence of febrile neutropenia (2.41% vs. 7.56% OR = 0.35), severe neutropenia (21.76% vs. 41.91% OR = 0.57), anemia (18.02% vs. 32.41% OR = 0.51), and thrombocytopenia (20.06% vs. 31.25% OR = 0.62). Utilization of cytopenia-supportive therapies, including granulocyte colony-stimulating factor use (40.47% vs. 81.01% OR = 0.61) and RBC transfusions (16.66% vs. 18.25% OR = 0.59) were significantly lower in the trilaciclib cohort as compared to control. The overall response rate (mean difference = 1.09,95% CI = 0.74–1.60) and overall survival (OR = -0.02 95% CI = -0.95-0.92) were similar, and progression-free survival was noted to be longer in the trilaciclib group (mean difference = 1.75, 95% CI = 0.75-2.75). Conclusions: Trilaciclib use consistently demonstrated efficacy in reducing CIM, thus lowering cytopenia-related healthcare utilization without compromising treatment efficacy in trials and real-world settings. Its novel mechanism of action offers great promise, and further studies with larger sample sizes on various cancers will corroborate existing evidence.

Effectiveness and safety of granulocyte colony-stimulating factor priming regimen for acute myeloid leukemia: A systematic review and meta-analysis of the Clinical Practice Guideline for the use of G-CSF 2022 from the Japan Society of Clinical Oncology.

The outcomes of relapsed or refractory acute myeloid leukemia (AML) remain poor. Although the concomitant use of granulocyte colony-stimulating factor (G-CSF) and anti-chemotherapeutic agents has been investigated to improve the antileukemic effect on AML, its usefulness remains controversial. This study aimed to investigate the effects of G-CSF priming as a remission induction therapy or salvage chemotherapy. We performed a thorough literature search for studies related to the priming effect of G-CSF using PubMed, Ichushi-Web, and the Cochrane Library. A qualitative analysis of the pooled data was performed, and risk ratios (RRs) with confidence intervals (CIs) were calculated and summarized. Two reviewers independently extracted and accessed the 278 records identified during the initial screening, and 62 full-text articles were assessed for eligibility in second screening. Eleven studies were included in the qualitative analysis and 10 in the meta-analysis. A systematic review revealed that priming with G-CSF did not correlate with an improvement in response rate and overall survival (OS). The result of the meta-analysis revealed the tendency for lower relapse rate in the G-CSF priming groups without inter-study heterogeneity [RR, 0.91 (95% CI 0.82-1.01), p=0.08; I2=4%, p=0.35]. In specific populations, including patients with intermediate cytogenetic risk and those receiving high-dose cytarabine, the G-CSF priming regimen prolonged OS. G-CSF priming in combination with intensive remission induction treatment is not universally effective in patients with AML. Further studies are required to identify the patient cohort for which G-CSF priming is recommended.