Use Of Granulocyte Colony-stimulating Factor Research Articles

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.

Therapeutic use of granulocyte colony-stimulating factor (G-CSF) in patients with febrile neutropenia: a comprehensive systematic review for clinical practice guidelines for the use of G-CSF 2022 from the Japan Society of Clinical Oncology.

Febrile neutropenia represents a critical oncologic emergency, and its management is pivotal in cancer therapy. In several guidelines, the use of granulocyte colony-stimulating factor (G-CSF) in patients with chemotherapy-induced febrile neutropenia is not routinely recommended except in high-risk cases. The Japan Society of Clinical Oncology has updated its clinical practice guidelines for the use of G-CSF, incorporating a systematic review to address this clinical question. The systematic review was conducted by performing a comprehensive literature search across PubMed, the Cochrane Library, and Ichushi-Web, focusing on publications from January 1990 to December 2019. Selected studies included randomized controlled trials (RCTs), non-RCTs, and cohort and case-control studies. Evaluated outcomes included overall survival, infection-related mortality, hospitalization duration, quality of life, and pain. The initial search yielded 332 records. Following two rounds of screening, two records were selected for both qualitative and quantitative synthesis including meta-analysis. Regarding infection-related mortality, the event to case ratio was 5:134 (3.73%) in the G-CSF group versus 6:129 (4.65%) in the non-G-CSF group, resulting in a relative risk of 0.83 (95% confidence interval, 0.27-2.58; p = 0.54), which was not statistically significant. Only median values for hospitalization duration were available from the two RCTs, precluding a meta-analysis. For overall survival, quality of life, and pain, no suitable studies were found for analysis, rendering their assessment unfeasible. A weak recommendation is made that G-CSF treatment not be administered to patients with febrile neutropenia during cancer chemotherapy. G-CSF treatment can be considered for patients at high risk.

Abstract PO2-18-02: Utilization of Granulocyte Colony-Stimulating Factor (GCSF) in the Management of Patients (pts) on Sacituzumab Govitecan-hziy (SG) and Impact on Duration of Therapy (DOT)

Abstract Background: An examination was conducted to understand the prevalence of neutropenia in pts managed with SG in the real-world setting, as the ASCENT trial demonstrated a 63% rate of neutropenia in those pts treated with SG1. In addition, an assessment was performed to see whether pts who developed neutropenia on SG received a GCSF and how GCSF use impacted pt DOT on SG. Methods: This assessment utilized the Integra Connect PrecisionQ real-world de-identified database of over 2 million cancer pts across 500 sites of care to evaluate the prevalence of neutropenia (< 1500 neutrophils) among those who were treated with SG, GCSF utilization among those with neutropenia, and the difference in DOT between neutropenic pts who received a GCSF and those who did not. In analyzing the DOT, pts were required to have had a follow-up of 12 months or greater. The SG pts data utilized reflects treatments through May 31, 2023. Comparisons of median DOT were conducted using a Wilcoxon Rank Sum test. Descriptive analyses were used to summarize pt demographic statistics. Results: 447 pts treated with SG were identified with an average age at treatment start of 58.5 (median of 60); 15% identified as Black or African American and 69% identified as White or Caucasian. Of the 447 pts treated with SG, 98% (N = 438) developed neutropenia while on therapy. Among those 438 pts who developed neutropenia, 61% received a GCSF and 39% did not. Of the 330 pts with at least 12 months of follow-up, the median DOT was 119.5 days. Among the 204 pts who received a GCSF, the median DOT was 147 days, compared to a median DOT of 97 days for the 126 pts who did not receive a GCSF (p < 0.001). Conclusion: The DOT for pts treated with SG who received a GCSF was longer than those who did not receive a GCSF while treated with SG. This assessment revealed that approximately 40% of SG treated pts who developed neutropenia did not receive a GCSF. Thus, increasing utilization of GCSFs presents an opportunity to improve management of pts who develop neutropenia while on SG to extend the time on therapy and potentially delay disease progression. These findings warrant further research on the use of prophylactic GCSFs for managing pts who receive SG and suggest further clinical guidance may be needed to provide best practices for managing pts on SG. [1] Rugo, H.S., Tolaney, S.M., Loirat, D. et al. Safety analyses from the phase 3 ASCENT trial of sacituzumab govitecan in metastatic triple-negative breast cancer. npj Breast Cancer 8, 98 (2022). https://doi.org/10.1038/s41523-022-00467-1 Citation Format: Vikram Gorantla, Erin Alwon, Mike Gart, John Li, Simon Blanc, Dawn Brenneman, Emma Genser, Prateesh Varughese, Justin Scott, Harvey Katzen. Utilization of Granulocyte Colony-Stimulating Factor (GCSF) in the Management of Patients (pts) on Sacituzumab Govitecan-hziy (SG) and Impact on Duration of Therapy (DOT) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-18-02.

Mesenteric panniculitis on 18F-FDG-PET/CT caused by G-CSF therapy mimicking recurrence of lymphoma

We present the case of a 55-year-old woman with Follicular Lymphoma, with basal 18F-FDG-PET/TC showing supra and infradiaphragmatic lymphatic, pleural and bone involvement. Treatment with Epcoritamab + Lenalidomide + Rituximab was iniciated with complete metabolic response (CR). Due to neutropenia, granulocyte colony-stimulating factor (G-CSF) was indicated on 02/22/23 for 5 days. A control PET/CT was performed on 02/23/23 with a pathological increase in metabolism in new-appearing mesenteric soft tissue lesions, suggestive of disease relapse. QT continued without changes and a PET/CT performed on 04/12/23 showed disappearance of the hypermetabolic mesenteric lesions. This suggests that it was a mesenteric panniculitis probably due to the use of G-CSF.

How Can Oncology Nurses and Advanced Practice Providers Reduce the Burden of Chemotherapy-Induced Febrile Neutropenia in the US?

Background: Neutropenia and febrile neutropenia (FN) are serious complications of myelosuppressive chemotherapy and present a considerable burden to patients with cancer. Febrile neutropenia is associated with increased risks of infection and hospitalization, a particular concern during the coronavirus disease 2019 (COVID-19) pandemic. Oncology nurses and advanced practice providers (APPs; including nurse practitioners, physician assistants, advanced practice nurses, and pharmacists) play a vital role in the management of patients with cancer and the prevention of infections. Objectives: The objectives of this article are to summarize the burden of chemotherapy-related neutropenia and FN in patients with cancer in the US and to evaluate the role of oncology nurses and APPs in preventing and managing FN. Methods: This article provides a narrative review of US studies reporting on the burden of FN, FN during COVID-19, adherence to guidelines for the use of prophylactic granulocyte colony-stimulating factors (G-CSFs), the involvement of oncology nurses in FN prevention, management, and patient quality of life, and inappropriate and/or incomplete G-CSF treatment. Findings: Despite advances in supportive care for patients with cancer receiving myelosuppressive chemotherapy, neutropenia and FN present a considerable burden to patients, particularly during the COVID-19 pandemic. Oncology nurses and APPs play a vital role in the appropriate and timely delivery of supportive care, which can improve patient outcomes and minimize treatment costs.

Comparison between a single dose of PEG G-CSF and multiple doses of non-PEG G-CSF: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) is widely used for the primary prophylaxis of febrile neutropenia (FN). Two types of G-CSF are available in Japan, namely G-CSF chemically bound to polyethylene glycol (PEG G-CSF), which provides long-lasting effects with a single dose, and non-polyethylene glycol-bound G-CSF (non-PEG G-CSF), which must be sequentially administrated for several days. This current study investigated the utility of these treatments for the primary prophylaxis of FN through a systematic review of the literature. 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 or meta-analysis was conducted to evaluate six outcomes. Through the first and second screenings, 23 and 18 articles were extracted for qualitative synthesis and meta-analysis, respectively. The incidence of FN was significantly lower in the PEG G-CSF group than in the non-PEG G-CSF group with a strong quality/certainty of evidence. The differences in other outcomes, such as overall survival, infection-related mortality, the duration of neutropenia (less than 500/μL), quality of life, and pain, were not apparent. A single dose of PEG G-CSF is strongly recommended over multiple-dose non-PEG G-CSF therapy for the primary prophylaxis of FN.

Effectiveness of G-CSF in chemotherapy for digestive system tumors: a systematic review of the Clinical Practice Guidelines for the Use of G-CSF 2022 delineated by the Japan Society of Clinical Oncology.

Granulocyte colony-stimulating factor (G-CSF) reportedly reduces the risk of neutropenia and subsequent infections caused by cancer chemotherapy. Although several guidelines recommend using G-CSF in primary prophylaxis according to the incidence rate of chemotherapy-induced febrile neutropenia (FN), the effectiveness of G-CSF in digestive system tumor chemotherapy remains unclear. To address these clinical questions, we conducted a systematic review as part of revising the Clinical Practice Guidelines for the Use of G-CSF 2022 published by the Japan Society of Clinical Oncology. This systematic review addressed two main clinical questions (CQ): CQ1: "Is primary prophylaxis with G-CSF effective in chemotherapy?", and CQ2: "Is increasing the intensity of chemotherapy with G-CSF effective?" We reviewed different types of digestive system tumors, including esophageal, gastric, pancreatic, biliary tract, colorectal, and neuroendocrine carcinomas. PubMed, Cochrane Library, and Ichushi-Web databases were searched for information sources. Independent systematic reviewers conducted two rounds of screening and selected relevant records for each CQ. Finally, the working group members synthesized the strength of evidence and recommendations. After two rounds of screening, 5/0/3/0/2/0 records were extracted for CQ1 of esophageal/gastric/pancreatic/biliary tract/colorectal/ and neuroendocrine carcinoma, respectively. Additionally, a total of 2/6/1 records were extracted for CQ2 of esophageal/pancreatic/colorectal cancer, respectively. The strength of evidence and recommendations were evaluated for CQ1 of colorectal cancer; however, we could not synthesize recommendations for other CQs owing to the lack of records. The use of G-CSF for primary prophylaxis in chemotherapy for colorectal cancer is inappropriate.

79 The routine use of Granulocyte-colony stimulating factor (G-CSF) with chemo-immunotherapy does not affect clinical outcomes in lung adenocarcinoma

79 The routine use of Granulocyte-colony stimulating factor (G-CSF) with chemo-immunotherapy does not affect clinical outcomes in lung adenocarcinoma

Effectiveness and safety of primary prophylaxis of G-CSF during chemotherapy for prostate cancer, Japanese clinical guideline for appropriate use of G-CSF: clinical practice guidelines for the use of G-CSF 2022.

Docetaxel (DTX) is commonly used as a primary chemotherapy, and cabazitaxel (CBZ) has shown efficacy in patients who are DTX resistant. Primary prophylactic granulocyte colony stimulating factor (G-CSF) therapy is currently used with CBZ treatment in routine clinical care in Japan. In this study, we performed a systematic review following the Minds guidelines to investigate the effectiveness and safety of primary prophylaxis with G-CSF during chemotherapy for prostate cancer and to construct G-CSF guidelines for primary prophylaxis use during chemotherapy. A comprehensive literature search of various electronic databases (PubMed, Cochrane Library, and Ichushi) was performed on January 10, 2020, to identify studies published between January 1990 and December 31, 2019 that investigate the impact of primary prophylaxis with G-CSF during CBZ administration on clinical outcomes. Ultimately, nine articles were included in the qualitative systematic review. Primary G-CSF prophylaxis during CBZ administration for metastatic castration-resistant prostate cancer was difficult to assess in terms of correlation with overall survival, mortality from infection, and patients' quality of life. These difficulties were owing to the lack of randomized controlled trials comparing patients with and without primary prophylaxis of G-CSF during CBZ administration. However, some retrospective studies have suggested that it may reduce the incidence of febrile neutropenia. G-CSF may be beneficial as primary prophylaxis during CBZ administration for metastatic castration resistant prostate cancer, and we made a "weak recommendation to perform" with an annotation of the relevant regimen.

Optimal timing of prophylactic pegylated G-CSF after chemotherapy administration for patients with cancer: a systematic review and meta-analysis from Clinical Practice Guidelines for the use of G-CSF 2022.

The timing of prophylactic pegylated granulocyte colony-stimulating factor (G-CSF) administration during cancer chemotherapy varies, with Day 2 and Days 3-5 being the most common schedules. Optimal timing remains uncertain, affecting efficacy and adverse events. This systematic review sought to evaluate the available evidence on the timing of prophylactic pegylated G-CSF administration. Based on the Minds Handbook for Clinical Practice Guideline Development, we searched the PubMed, Ichushi-Web, and Cochrane Library databases for literature published from January 1990 to December 2019. The inclusion criteria included studies among the adult population using pegfilgrastim. The search strategy focused on timing-related keywords. Two reviewers independently extracted and assessed the data. Among 300 initial search results, only four articles met the inclusion criteria. A meta-analysis for febrile neutropenia incidence suggested a potential higher incidence when pegylated G-CSF was administered on Days 3-5 than on Day 2 (odds ratio: 1.27, 95% CI 0.66-2.46, p = 0.47), with a moderate certainty of evidence. No significant difference in overall survival or mortality due to infections was observed. The trend of severe adverse events was lower on Days 3-5, without statistical significance (odds ratio: 0.72, 95% CI 0.14-3.67, p = 0.69) and with a moderate certainty of evidence. Data on pain were inconclusive. Both Day 2 and Days 3-5 were weakly recommended for pegylated G-CSF administration post-chemotherapy in patients with cancer. The limited evidence highlights the need for further research to refine recommendations.

Abstract 6327: Impact of G-CSF on safety and efficacy of CAR T-cell therapy in non-Hodgkin lymphoma

Abstract Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy is an established treatment modality for the management of refractory and/or relapsed non-Hodgkin lymphoma (NHL). Despite restrictions on granulocyte colony-stimulating factor (G-CSF) use in registration clinical trials due to potential worsening of cytokine release syndrome (CRS), G-CSF is often prescribed for neutrophil recovery post-CAR-T in clinical practice. We conducted a retrospective study to assess the association between G-CSF use and the safety and efficacy of CAR-T. Methods: Following Institutional Review Board approval, we retrospectively analyzed NHL patients receiving commercial CD19-targeted CAR-T across Mayo Clinic sites (Arizona, Florida, and Minnesota) between October 2017 and May 2023. Demographics, labs, and post CAR-T events were collected. Electronic medical records were reviewed for G-CSF exposure within Day 1 - 100 post-CAR T. Differences by G-CSF status were examined using a Chi-square test and Kruskal Wallis tests. Hazard ratios (HR) and 95% confidence intervals (CI) for overall survival (OS) were calculated using Cox model. Results: Among 270 CAR-T patients; 106 received G-CSF within 30 days and 164 did not. Median age was 56.9 with G-CSF and 58.3 without G-CSF. Most were male (75.2% G-CSF, 62.6% no G-CSF). Diffuse large B cell lymphoma was the predominant NHL subtype (67.0% G-CSF, 65.2% no G-CSF). G-CSF within 30 days was not associated with reduced incidence of neutropenic fever (11.7% G-CSF vs 9.9% no G-CSF, p = 0.6593) or documented infection (22.1% vs 18.3%, p = 0.4439). G-CSF correlated with decreased profound neutropenia duration (ANC < 100 μL, 0 vs 2 days, p < 0.0001) and incidence within 30 days ( 31.7% vs 60.4%, p < 0.0001) as well as incidence of protracted profound neutropenia (> 7 days, 3.8% vs 22.8%, p < 0.0001). G-CSF was associated with a higher incidence of cytopenias between days 30 -100: severe neutropenia (ANC < 500/uL, 28.8% vs 15.2%, p = 0.0075), severe anemia (Hb < 8 g/dL, 21% vs 9.7%, p = 0.0114), and severe thrombocytopenia (Plt < 50 g/L, 35.2% vs 20.9%, p = 0.0099). Logistic regression analysis showed that none of the examined covariates, including prior autologous stem cell transplant, ECOG PS score, and receipt of bridging therapy, were associated with severe neutropenia likelihood. G-CSF was associated with a higher CRS incidence (89.6% vs 79.9%, p = 0.0343), but grade 3 CRS or higher (4.7% vs 3.7%, p = 0.6675) was no different. No difference in complete response rates (66% vs 61.1%, p = 0.4707) or 2-year OS (p = 0.523) was observed between the 2 groups. Conclusion: G-CSF within 30 days was associated with reduced duration and incidence of profound neutropenia without a significant impact on incidence of neutropenic fever or documented infections. There was a signal of association between G-CSF and increased incidence of low-grade CRS and delayed cytopenias (day 30-100) that warrants confirmation in larger studies. Citation Format: Lay She Ng, Claire I. Yee, Radhika Bansal, Mohamed A. Kharfan-Dabaja, Grzegorz S. Nowakowski, Allison C. Rosenthal, Javier Munoz, Januario Castro, Wern Lynn Ng, Hemant S. Murthy, Yi Lin, Matthew R. Buras, Madiha Iqbal, Yucai Wang, Talal Hilal. Impact of G-CSF on safety and efficacy of CAR T-cell therapy in non-Hodgkin lymphoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 6327.

Effectiveness and safety of primary prophylaxis of granulocyte colony-stimulating factor during dose-dense chemotherapy for urothelial cancer: Clinical Practice Guidelines for the Use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) decreases the incidence, duration, and severity of febrile neutropenia (FN); however, dose reduction or withdrawal is often preferred in the management of adverse events in the treatment of urothelial cancer. It is also important to maintain therapeutic intensity in order to control disease progression and thereby relieve symptoms, such as hematuria, infection, bleeding, and pain, as well as to prolong the survival. In this clinical question, we compared treatment with primary prophylactic administration of G-CSF to maintain therapeutic intensity with conventional standard therapy without G-CSF and examined the benefits and risks as major outcomes. A detailed literature search for relevant studies was performed using PubMed, Ichu-shi Web, and Cochrane Library. Data were extracted and evaluated independently by two reviewers. A qualitative analysis of the pooled data was performed, and the risk ratios with corresponding confidence intervals were calculated and summarized in a meta-analysis. Seven studies were included in the qualitative analysis, two of which were reviewed in the meta-analysis of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) therapy, and one randomized controlled study showed a reduction in the incidence of FN. Primary prophylactic administration of G-CSF may be beneficial, as shown in a randomized controlled study of dose-dense MVAC therapy. However, there are no studies on other regimens, and we made a "weak recommendation to perform" with an annotation of the relevant regimen (dose-dense MVAC).

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.

The Use of Granulocyte Colony-Stimulating Factor as Primary Prophylaxis in Patients Undergoing Chemotherapy: An Experience of Moroccan Oncologists.

Febrile neutropenia (FN) is a frequent and serious emergency for oncologic patients undergoing chemotherapy. Using granulocyte colony-stimulating factor (G-CSF) as primary prophylaxis of febrile neutropenia is an integral part of the management of cancer patients. Our study aims to identify the challenges that prevent Moroccan oncologists from prescribing G-CSF for primary prevention. Seventy doctors participated in our study, with a participation rate of 35.35%. Twenty-two participants had at least five years of experience in oncology. Most participants were medical oncologists (82.9%), and two-thirds of them practiced in teaching hospitals. Regarding the use of G-CSF in primary prevention, all participants complied with the recommendations for FN risk assessment and the prescription of G-CSF for prophylaxis in patients at high risk of FN (>20%). However, their use in intermediate-risk patients remains limited mainly by the cost of these drugs (45.7% of participants). FN remains a dreadful complication in oncology. Since the introduction of G-CSF into standard oncology practice, particularly in primary prevention, the management of certain patients has improved considerably. Nevertheless, the indications for G-CSF in our context, essentially in intermediate-risk patients, are uncertain.

Effectiveness and safety of primary prophylaxis with G-CSF for lung cancer: a systematic review and meta-analysis to develop clinical practice guidelines for the use of G-CSF 2022.

Granulocyte colony-stimulating factor (G-CSF) is commonly administered to cancer patients undergoing myelosuppressive chemotherapy, especially when incidence rate of febrile neutropenia (FN) surpasses 20%. While primary prophylaxis with G-CSF has been proven effective in preventing FN in patients with cancer, there is limited evidence regarding its efficacy in specifically, lung cancer. Our systematic review focused on the efficacy of G-CSF primary prophylaxis in lung cancer. We extracted studies on non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) using the PubMed, Ichushi Web, and Cochrane Library databases. Two reviewers assessed the extracted studies for each type of lung cancer and conducted quantitative and meta-analyses of preplanned outcomes, including overall survival, FN incidence, infection-related mortality, quality of life, and musculoskeletal pain. A limited number of studies were extracted: two on NSCLC and six on SCLC. A meta-analysis was not conducted owing to insufficient data on NSCLC. Two case-control studies explored the efficacy of primary prophylaxis with G-CSF in patients with NSCLC (on docetaxel and ramucirumab therapy) and indicated a lower FN frequency with G-CSF. For SCLC, meta-analysis of five studies showed no significant reduction in FN incidence, with an odds ratio of 0.38 (95% confidence interval 0.03-5.56, P = 0.48). Outcomes other than FN incidence could not be evaluated due to low data availability. Limited data are available on G-CSF prophylaxis in lung cancer. Primary prophylaxis with G-CSF may be weakly recommended in Japanese patients with NSCLC undergoing docetaxel and ramucirumab combination therapy.

Incidence of pulmonary toxicity in bleomycin-containing regimens for testicular cancer with and without the use of growth factor.

The concurrent use of bleomycin and granulocyte colony-stimulating factors (G-CSFs) has historically been debated as a risk factor for bleomycin-induced pulmonary toxicity in patients with both testicular cancer and Hodgkin's lymphoma. The purpose of this study is to evaluate the incidence of pulmonary toxicity in patients with testicular cancer who were treated with bleomycin and pegfilgrastim concurrently. This is a retrospective study that includes male patients over the age of 18 years old diagnosed with testicular cancer who received bleomycin-containing chemotherapy regimens with and without the use of G-CSF agents. There were a total of 33 patients identified as receiving bleomycin, with 30 of those patients having received concurrent G-CSF therapy. Of the patients who received G-CSF therapy, 11 patients (36.6%) experienced pulmonary toxicity leading to discontinuation of bleomycin or changes in chemotherapy regimens altogether. There were no major differences in patient demographics or risk factors between those who received G-CSF and developed pulmonary toxicity and those who received G-CSF but did not develop pulmonary toxicity. Further studies are needed in order to fully assess the risk of pulmonary toxicity with this chemotherapy regimen.

Impact of primary prophylaxis (PP) with granulocyte colony-stimulating factor on the outcomes of patients with locally advanced gastric cancer treated with FLOT: A single-center retrospective analysis.

414 Background: The role of primary prophylaxis (PP) with granulocyte colony-stimulating factor (G-CSF) for patients with locally advanced gastric cancer (LAGC) treated with FLOT is currently unknown. Although original FLOT4 study did not recommend PP, the use of G-CSF is common in clinical practice to avoid serious complications. However, its use is associated with increased financial costs. Methods: This is a retrospective, single-institution study. We included patients with pathologically confirmed LAGC who received perioperative FLOT4. Patients were categorized in two groups: PP versus no- PP. Our objectives were to compare frequency of grades 3 or 4 neutropenia (G3/4N) and febrile neutropenia (FN) between PP and non-PP patients. We also evaluate the association between pathological complete response (pCR) and disease-free survival (DFS) and overall survival (OS) according to the use of PP. Binomial variables were compared using Fisher's exact test. Kaplan-Meier method was used to calculate median DFS and OS and respective 95% confidence intervals [95%CI] and any difference assessed by the log-rank test. Results: From January 2019 until December 2022, 122 LAGC patients were treated with perioperative FLOT. Median age was 56 years, 53.2% were female and 84.4% were ECOG 0. Primary prophylaxis (PP) was used by 58 patients (47.5%); there was no difference between clinical and tumor features between both groups regarding age, sex, ECOG, T and N staging and Lauren’s subtype. PP costs raised treatment costs up to 15%. Grade 3 or 4 neutropenia occurred more frequently among patients without PP (65.6 vs. 1.7%; p < 0.001). There was no difference in the frequency of FN between groups (7.8 vs. 0%; p = 0.06). Overall patients, pCR occurred in 11.8% os patients. Regarding the influence of PP in pathological response after FLOT chemotherapy, there was no difference between PP vs non-PP patients with pCR (14.3% vs 9.5%, p = 0.57). Median follow-up was 27.4 (range 2.8 – 70.6 months). Twenty-six patients (21.3%) died during follow-up. Median OS was 52.5 months (95% CI: 47.1-57.8). Median OS for patients in PP and no PP groups were 44.5 and 56.2 months (log-rank P =0.06), respectively. Median DFS was 43.1 months (95% CI: 37.2-48.9). Median DFS for patients in PP and no PP groups were 39.6 and 43.5 months (log-rank P =0.80), respectively. Conclusions: Despite the reduction in the frequency of G3/4N, rates of FN among patients treated with FLOT with G-CSF are too low to justify its use in a routine basis. Furthermore, PP is not associated with relevant clinical endpoints such as pCR neither OS or DFS. Based on this, PP in such situations should not be routinely used due to its financial costs.

Drug-induced pneumonitis risk in diffuse large B-cell/follicular lymphoma patients treated with R-CHOP-like regimen is associated with the use of granulocyte colony-stimulating growth factors.

Rituximab-based combinations are the standard of care in diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL). Despite being on market for over 20 years, some of the adverse effects associated with the use of rituximab are not well known. Drug-induced interstitial pneumonitis (DIP) is a potentially fatal complication of the treatment. Granulocyte colony-stimulating factors (G-CSF) are supportive agents commonly used to prevent neutropenic infections. G-CSF are reported to have pulmonary toxicity, but the risk of DIP is greater when used in combination with other potentially pulmotoxic agents. In this retrospective study, we reported the G-CSF use and risk of DIP in 234 DLBCL patients and 87 FL patients receiving R-CHOP-type immunochemotherapy. In 72% of patients, the treatment included a G-CSF support. The overall incidence of treatment-induced pneumonitis was 6.9% in this patient group. All the DIP cases (n = 16) were among patients receiving G-CSF support (p = 0.03). Older age (over 60 years) and higher disease stage (Ann Arbor 3-4) also increased the risk of DIP. These findings suggest that the use of G-CSF increases the risk of DIP, when used in combination with rituximab-containing regimen.