Chemotherapy-induced Neutropenia In Patients Research Articles

Prognostic value of body composition measures in breast cancer patients treated with chemotherapy

Breast cancer remains a significant public health issue, often resulting in severe side effects such as neutropenia, highlighting the need for reliable predictors of clinical outcomes. This study aimed to evaluate the predictive value of body composition measures for mortality, recurrence, and chemotherapy-induced neutropenia in patients with breast cancer following surgery and chemotherapy. We retrospectively analyzed 85 breast cancer patients who underwent surgery and chemotherapy between 2006 and 2016. Body composition was assessed using computed tomography (CT) or positron emission tomography (PET) at diagnosis and three years and five years post-diagnosis. Metrics included skeletal muscle area (SMA), skeletal muscle index (SMI), subcutaneous adipose tissue area (SAT), and visceral adipose tissue area (VAT). Longitudinal analysis revealed a decrease in muscle mass (P < 0.001 for both SMA and SMI) and nonsignificant changes in fat mass (P = 0.449 for SAT and P = 0.798 for VAT). A lower SMI at diagnosis was significantly associated with increased mortality (P = 0.019) and a higher incidence of grade 4 neutropenia (P = 0.008). There was no significant association between SMI at diagnosis and recurrence (P = 0.691). No associations were found between body composition measurements during the follow-up period and the clinical outcomes. Lower skeletal muscle mass at diagnosis is strongly associated with higher mortality and chemotherapy-induced complications in patients with breast cancer, highlighting the potential of readily available imaging techniques as valuable predictors of clinical outcomes.

A randomized, multicenter phase III Study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer

BackgroundF-627 (efbemalenograstim alfa) is a novel long acting granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This studyevaluated the efficacy and safety of F-627, also known as efbemalenograstim alfa (Ryzneuta®) in reducing neutropenia compared with filgrastim (GRAN®).MethodsThis was a multicenter, randomized, open-label, active-controlled non-inferiority study. Two hundred thirty nine (239) patients were enrolled in thirteen centers and received the chemotherapy with epirubicin (100 mg/m2) and cyclophosphamide (600 mg/m2) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive either a single 20 mg subcutaneous (s.c.) injection of F-627 on day 3 of each cycle or daily s.c. injection of filgrastim 5 µg/kg/d starting from day 3 of each cycle. The primary endpoint was the duration of grade 3 or 4 neutropenia in cycle 1. The safety profile was also evaluated.ResultsThe mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.68 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimate of the between-group median difference (F-627 vs filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of the one-sided 97.5% CI was 0 day, which was within the prespecified non-inferiority margin of 1-day. Results for all efficacy endpoints in cycles 2 − 4 were consistent with the results in cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed in the F-627 group compared with the filgrastim group. The ANC nadir in the F-627 group was significantly higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as standard daily filgrastim.ConclusionsA single fixed dose of 20 mg of F-627 in each cycle was as safe and effective as a daily dose of filgrastim 5 µg/kg/d in reducing neutropenia and its complications in patients who received four cycles of EC.Trial registrationClinicalTrials.gov: NCT04174599, on 22/11/2019.

Clinical outcomes of coronavirus disease in patients with breast cancer treated with granulocyte colony-stimulating factor following chemotherapy: Triangulation of evidence using population-based cohort and Mendelian randomization analyses.

Recombinant human granulocyte colony-stimulating factor (G-CSF) administration in patients with cancer and coronavirus disease (COVID-19) remains controversial. Concerns exist that it may worsen COVID-19 outcomes by triggering an inflammatory cytokine storm, despite its common use for managing chemotherapy-induced neutropenia (CIN) or febrile neutropenia post-chemotherapy. Here, we determined whether prophylactic or therapeutic G-CSF administration following chemotherapy exacerbates COVID-19 progression to severe/critical conditions in breast cancer patients with COVID-19. Between December 2022 and February 2023, all 503 enrolled breast cancer patients had concurrent COVID-19 and received G-CSF post-chemotherapy, with most being vaccinated pre-chemotherapy. We prospectively observed COVID-19-related adverse outcomes, conducted association analyses, and subsequently performed Mendelian randomization (MR) analyses to validate the causal effect of genetically predicted G-CSF or its associated granulocyte traits on COVID-19 adverse outcomes. Only 0.99% (5/503) of breast cancer patients experienced COVID-19-related hospitalization following prophylactic or therapeutic G-CSF administration after chemotherapy. No mortality or progression to severe/critical COVID-19 occurred after G-CSF administration. Notably, no significant associations were observed between the application, dosage, or response to G-CSF and COVID-19-related hospitalization (all p >.05). Similarly, the MR analyses showed no evidence of causality of genetically predicted G-CSF or related granulocyte traits on COVID-19-related hospitalization or COVID-19 severity (all p >.05). There is insufficient evidence to substantiate the notion that the prophylactic or therapeutic administration of G-CSF after chemotherapy for managing CIN in patients with breast cancer and COVID-19 would worsen COVID-19 outcomes, leading to severe or critical conditions, or even death, especially considering the context of COVID-19 vaccination.

The occurrence and risk factors of chemotherapy-induced neutropenia in patients with breast cancer not receiving primary G-CSF prophylaxis.

Chemotherapy-induced neutropenia (CIN) is a substantial side effect in chemotherapy of breast cancer patients. Administration of granulocyte colony stimulating factor (G-CSF) that may reduce CIN occurrence is not commonly available to many local cases. To investigate the occurrence of grade 4 CIN and the influencing factors in breast cancer patients not receiving G-CSF prophylaxis. One-hundred and eighty-six newly diagnosed breast cancer patients who received a 3-weekly (neo)adjuvant or palliative chemotherapy without primary G-CSF prophylaxis were included. Grade 4 CIN was defined as absolute neutrophil count (ANC) <0.5 × 103/mm3 during any chemotherapy cycle. We used logistic regression to explore the association of clinical, pathological and treatment factors with the risk of grade 4 CIN in the first cycle and in any given cycle. Fifty-seven (30.6%) patients experienced grade 4 CIN in the first cycle and 145 (78%) had it at least once during chemotherapy. In the first cycle, haemoglobin, ANC, and albumin levels were associated with grade 4 CIN (OR = 1.48, p = 0.031; OR = 0.68, p = 0.006; and OR = 2.07, p = 0.042). In any cycle, pre-treatment ANC levels and anthracycline-taxane combination regimen were associated with grade 4 CIN (OR = 0.78, p = 0.032 and OR = 3.64, p = 0.012). A significant proportion of the local breast cancer cases undergoing chemotherapy without primary G-CSF prophylaxis experienced grade 4 CIN. Haemoglobin, ANC, and albumin levels are the risk factors for first cycle CIN, while pre-treatment ANC levels and anthracycline-taxane chemotherapy regimen are associated with CIN in any given cycle. These risk factors may be used to direct a recommendation of G-CSF prophylaxis to the most at-risk individuals in the local setting or other settings in similar situations.

P-63 Real-world UK retrospective multi-centre review of the use of G-CSF in the prevention of chemotherapy-induced neutropenia in patients with CRC receiving trifluridine/tipiracil

P-63 Real-world UK retrospective multi-centre review of the use of G-CSF in the prevention of chemotherapy-induced neutropenia in patients with CRC receiving trifluridine/tipiracil

350P Primary prevention of chemotherapy-induced neutropenia in patients with advanced lung cancer in real-world research

Targeted therapy and immunotherapy opens a new era in the treatment of lung cancer. However, for the majority of patients who do not harbor certain molecular alterations, chemotherapy still plays a critical role in the treatment strategy. Neutropenia is a major dose-limiting toxicity of myelosuppressive chemotherapy and has been commonly found in lung cancer patients treated with platinum-based chemotherapy. Mecapegfilgrastim (code name HHPG-19K), a long-acting PEGrhG-CSF and a biosimilar to pegfilgrastim.

Abstract P5-16-14: A randomized, multicenter phase III study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting dimeric rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer

Abstract Background: Neutropenia is common in patients receiving myelotoxic chemotherapy. F-627( efbemalenograstim alfa ), is a novel long acting dimeric granulocyte colony-stimulating factor (G-CSF) that contains two human G-CSF fused to a human immunoglobulin G2 (hIgG2) -Fc fragment with a peptide linker. This study was to evaluate the efficacy and safety of F-627 for reducing chemotherapy-induced neutropenia as compared with filgrastim (GRAN®). Methods: This was a multicenter, randomized, open-label, and active-controlled non-inferiority study. Thirteen centers enrolled 239 patients who received chemotherapy with epirubicin (100mg/m2) and cyclophosphamide (600 mg/m2) (EC therapy) on day 1 of each cycle for a maximum of four cycles. Patients were randomized to receive on day 3 either a single 20 mg subcutaneous (s.c.) injection of F-627 per cycle or daily s.c injections of filgrastim 5 μg/kg/day. The primary endpoint was the duration of grade 3 (ANC &amp;lt;1× 109/L) or 4 (ANC&amp;lt;0.5× 109/L) neutropenia in cycle 1. The safety profile was evaluated. Results: The mean (SD) duration of grade 3 or 4 neutropenia in cycle 1 was 0.67 (1.10) and 0.71 (0.95) days for the F-627 and the filgrastim groups, respectively. The Hodges-Lehmann estimator of the median difference between groups (F-627 − Filgrastim) in the duration of grade 3 or 4 neutropenia in cycle 1 was 0 day and the upper limit of one-sided 97.5% CI was 0 days, which was within the 1-day prespecified non-inferiority margin. Results for all efficacy end points in cycles 2−4 was consistent with the results from cycle 1, however a trend towards a lower incidence and a shorter duration of grade 3 or 4 neutropenia and grade 4 neutropenia was observed with F-627 compared with filgrastim. The nadir in the F-627 group was higher than that in the filgrastim group in each cycle. A single fixed dose of F-627 was well tolerated and as safe as multiple daily doses of filgrastim. The most frequently reported adverse events considered to be related to the study drug were bone pain and back pain. No deaths occurred during the study. 5.0% of F-627 patients and 6.7% of filgrastim patients reported serious adverse events (SAEs). The incidence of SAEs was low in both groups and no SAEs were related to study drugs, and were resolved during the study. Conclusions: A single fixed dose of 20 mg of F-627 was as safe and effective as multiple daily doses of filgrastim 5μg/kg/day in reducing chemotherapy-induced neutropenia and its complications in patients who received four cycles of EC therapy. F-627 provides the Chinese oncologists an alternative for simplifying the management of chemotherapy-induced neutropenia. The study was approved by the National Medical Products Administration of China (registration number: 2017L04033), and was registered on www.chinadrugtrials.org.cn (registration number: CTR20170705) and ClinicalTrials.gov (registration number: NCT04174599). Citation Format: William Daley, Zhimin Shao, Qingyuan Zhang, Hongshen Li, Changshen Ye, Shufang Wang, Langxi Zhang, Gaochong Zhang, Jianmin Chen. A randomized, multicenter phase III study of once-per-cycle administration of efbemalenograstim alfa (F-627), a novel long-acting dimeric rhG-CSF, for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P5-16-14.

Cost-Effectiveness Analysis of PEG-rhG-CSF as Primary Prophylaxis to Chemotherapy-Induced Neutropenia in Women With Breast Cancer in China: Results Based on Real-World Data.

Background: Pegylated recombinant human granulocyte colony-stimulating factors (PEG-rhG-CSFs) are more commonly and widely used than recombinant human granulocyte colony-stimulating factors (rhG-CSFs) in preventing chemotherapy-induced neutropenia in patients with stage II-IV breast cancer. To reduce the financial burden on these patients, the corresponding medical insurance directory needs to be revised. Objectives: To evaluate the cost-effectiveness of PEG-rhG-CSF versus rhG-CSF in patients with stage II-IV breast cancer in central China. Methods: Two Markov models, a chemotherapy model and a post-chemotherapy model, were developed to study the effects and costs, with a time horizon of 12 weeks and 35 years, respectively. Cost and probability input data were primarily obtained from a retrospective real-world study conducted in five tertiary hospitals. Propensity score matching was adopted to overcome retrospective bias. Other parameters were extracted from literature as well as advice from clinical experts. Univariate and probabilistic sensitivity analyses were conducted. Results: In the first chemotherapy model, PEG-rhG-CSF was associated with fewer episodes of febrile neutropenia (FN) (N = 19 per 1000 patients treated), infections (N = 24 per 1000 patients treated) and deaths (N = 2 per 1000 patients treated), but higher costs (¥36 more per patient treated). The post-chemotherapy model indicated that PEG-rhG-CSF led to higher gains in quality-adjusted life years (QALYs) (11.695 versus 11.516) in comparison to rhG-CSF. Sensitivity analysis showed that the cost of PEG-rhG-CSF had the greatest impact on the incremental costs, and incremental QALYs were very sensitive to the risk of RDI <85%. The probability of PEG-rhG-CSF being cost-effective compared to rhG-CSF was 66% at the willingness to pay (WTP) thresholds of ¥72,371 per QALY gained. Conclusion: According to this economic evaluation based on real-world data, PEG-rhG-CSF may be considered as a more cost-effective strategy relative to rhG-CSF for stage II-IV breast cancer patients in central China. However, to reflect a national perspective, further evidence is needed using data from larger-scale studies.

Prophylactic administration of mecapegfilgrastim after chemotherapy in patients with lymphoma.

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

Prognostic Implications of Chemotherapy-Induced Neutropenia in Stage III Colorectal Cancer

Previous studies have reported chemotherapy-induced neutropenia (CIN) as a prognostic factor in stage IV colorectal cancer (CRC). However, only few reports analyzed the prognostic value of CIN in patients with stage III CRC who received adjuvant chemotherapy with oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX). We aimed to investigate the prognostic implications of CIN in patients with stage III CRC who received adjuvant chemotherapy with FOLFOX. We retrospectively analyzed patients with stage III CRC who received adjuvant chemotherapy with FOLFOX at a tertiary hospital between January 2007 and December 2017. Severe CIN was defined as an absolute neutrophil count of less than 1000/mm3. Three-y disease-free survival (DFS) and overall survival (OS) were analyzed as primary endpoints. Among the 199 patients included in this study, 110 patients (55.3%) experienced severe CIN. There were no significant differences in survival outcomes between the control and CIN groups (control group versus CIN group: 3-y OS, 82.0 % versus 72.7 %; log rank, P=0.250 and 3-y DFS, 71.9 % versus 62.7; log rank, P=0.294). Univariate and multivariate analyses revealed that CIN did not affect DFS and OS in patients with stage III CRC who received adjuvant FOLFOX chemotherapy. Severe CIN occurring during adjuvant FOLFOX chemotherapy did not play a significant role in the prognosis of patients with stage III CRC.

Abstract PS9-59: Pooled efficacy analysis from two phase 3 studies in patients receiving eflapegrastim, a novel, long-acting granulocyte-colony stimulating factor, following TC for early-stage breast cancer

Abstract Background: Eflapegrastim (Rolontis®, Efla) represents the first novel, long-acting granulocyte-colony stimulating factor (G-CSF) to be introduced in more than 15 years. Efla consists of a recombinant human G-CSF analog conjugated to a human IgG4 Fc fragment via a polyethylene glycol linker. Preclinical, clinical, and pharmacodynamic/pharmacokinetic data have shown increased potency for Efla versus pegfilgrastim (Peg). Both independent, randomized Phase 3 studies comparing Efla and Peg for prophylaxis of chemotherapy-induced neutropenia in patients with early-stage breast cancer (ESBC) met the primary endpoint of non-inferiority in duration of severe neutropenia (SN; ANC&amp;lt;0.5 × 109/L) (p&amp;lt;0.001) for Efla vs Peg in all 4 treatment cycles. Additionally, one of the studies exhibited a statistically significant reduction in the relative risk of SN in Cycle 1 with Efla. Here we provide a pooled analysis across the two pivotal studies comparing Efla vs Peg for SN in various subgroups. Methods: Patients with ESBC, who were candidates for adjuvant or neoadjuvant chemotherapy, were randomized 1:1 in two open-label Phase 3 studies to fixed-dose Efla (3.6 mg G-CSF) or standard Peg (6 mg G-CSF) administered on Day 2 following TC (docetaxel/cyclophosphamide) for a total of 4 cycles. ANCs were collected daily in Cycle 1 and 5 times in Cycles 2-4. SN was evaluated between treatment groups in Cycle 1 using Fisher’s exact test at 5% level of significance and was analyzed using multivariate logistic and Cox proportional hazards regression models. Results: A total of 643 patients who received either Efla (n=314) or Peg (n=329) were included in the analysis. The two treatment groups were well balanced for demographics and baseline characteristics. The mean age was 59 years, 38% were ≥65 years old, and 54% weighed &amp;gt;75kg. The safety profiles, including AEs and discontinuations, for Efla and Peg were comparable, and &amp;gt;99% of all patients received full dose of TC on schedule. The majority (67%) of patients with SN experienced a 1 day duration, occurring between Days 7 and 8 after TC. Mean duration of SN for Efla was statistically lower than for Peg (0.24 vs. 0.36 days; p=0.029). The above statistical significance was maintained for Efla after adjusting for demographic and baseline characteristics, namely age, weight, enrolling geographical region, and treatment setting in a multivariate model. Similarly, the incidence of SN for Efla was statistically lower than Peg in Cycle 1 (17.5% vs 24%; relative risk reduction [RRR]=27%; p=0.043). Univariate analysis of the incidence of SN showed a significant risk reduction in favor of Efla (8.6% vs 14.1%; p=0.034) for patients weighing &amp;gt;75kg (p=0.034). Multivariate analysis of SN showed significant odds ratio of SN for age ≥65 years and baseline ANC &amp;gt;6 × 109/L in favor of Efla (OR=0.42 and 0.39, respectively). The incidence of SN in Cycles 2-4 was comparable between treatment groups. Also, the incidence of febrile neutropenia and neutropenic complications was similar with &amp;lt;5% in each treatment group. No leukocytosis, splenic rupture, or anaphylaxis was reported in any patient receiving Efla or Peg. Conclusion: A pooled analysis of two, randomized Phase 3 studies evaluating Efla vs Peg, administered once-per-cycle for prophylaxis of SN, showed Efla and Peg had similar safety profiles with Efla demonstrating a statistically significant risk reduction in SN overall and in patients weighing &amp;gt;75kg. Eflapegrastim is a novel, long-acting and potent recombinant human G-CSF which may provide an attractive option in supporting patients at risk for SN-related complications. Citation Format: Lee S Schwartzberg, Gajanan Bhat, Alvaro Restrepo, Osama Hlalah, Inderjit Mehmi, Yong Wha Moon, Seungjae Baek, Shanta Chawla, Francois Lebel, Patrick Wayne Cobb. Pooled efficacy analysis from two phase 3 studies in patients receiving eflapegrastim, a novel, long-acting granulocyte-colony stimulating factor, following TC for early-stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS9-59.

346P Occurence and risk factors of chemotherapy-induced neutropenia in patients with breast cancer: A hospital-based assessment in Indonesia

346P Occurence and risk factors of chemotherapy-induced neutropenia in patients with breast cancer: A hospital-based assessment in Indonesia

909P Efficacy and safety of HHPG-19K for prophylaxis of chemotherapy-induced neutropenia in patients with lymphoma

Neutropenia is a common complication of chemotherapy, which will lead to the delay or reduction of chemotherapy and affect the therapeutic effect. Mecapegfilgramtim (code name HHPG-19K), the novel long-acting rhG-CSF, has been developed. This study was evaluated the efficacy and safety of HHPG-19K for reducing neutropenia compared with un-prevention. This was a randomized, controlled non-inferiority study. A total of 151 lymphoma patients who were eligible for chemotherapy were randomly assigned into two groups, which received HHPG-19K fixed dosage of 6 mg or un-prevention in the first cycle of chemotherapy. The primary endpoint was the duration of grade≥3 neutropenia in cycle 1, incidence of grade≥3 neutropenia, and febrile neutropenia (FN). The safety profile was also evaluated. The adjusted mean duration of grade>1 neutropenia was 5 days in HHPG-19K fixed dosage of 6 mg group and 7 days in the un-prevention group (P<0.01). There was difference between the two groups in the incidence of grade≥3 neutropenia (P<0.01). There were 10 patients (12.82%) in HHPG-19K fixed dosage of 6 mg/kg group, 15 patients (20.55%) in un-prevention group experienced grade≥3 neutropenia. Compared with un-prevention group, the incidence of grade 4 neutropenia was significantly lower in patients treated with HHPG-19K fixed dosage of 6 mg/kg (7.69% vs 15.07%). For the incidence of FN, there were 5 patients (6.41%) in HHPG-19K fixed dosage of 6 mg/kg group, 11 patients (15.07%) in un-prevention group experienced FN (P<0.05). For safety profile, HHPG-19K group were all well-tolerated. The frequent AEs were ostalgia (13.70 vs 6.41%), fever (24.66% vs 11.54%), nausea (21.92% vs 1.28%), emesis (16.44% vs 1.28%), weakness (9.59% vs 2.56%) and others (19.18% vs 10.26%) during the chemotherapy, which were inferior to the un-prevention group (P<0.01). The frequent AEs were ostalgia (6.41 vs 13.70%), fever (11.54% vs 24.66%), nausea (1.28% vs 21.92%), emesis (1.28% vs 16.44%), weakness (2.56% vs 9.59%) and others (10.26% vs 19.18%) during the chemotherapy, which were inferior to the un-prevention group (P<0.01). No unexpected AE was observed. This study provided new evidence for HHPG-19K, which would be a new alternative clinical practice for prophylaxis of chemotherapy induced neutropenia.

Management of chemotherapy-induced neutropenia in patients with cancer: 2019 guidelines of the Italian Medical Oncology Association (AIOM).

Neutropenia is the most frequent side effect of commercially available myelosuppressive drugs and its most significant complication is febrile neutropenia. It is associated with increased hospital admissions and higher probability of death. Prophylaxis with the administration of granulocyte colony-stimulating factor can prevent neutropenia caused by anticancer drugs. The correct administration of these drugs and the management of febrile neutropenia are extremely important in the treatment of patients with cancer.

Efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor in the primary and secondary prevention of chemotherapy-induced neutropenia in patients with lymphoma.

e20061 Background: To evaluate the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, brand name: Jinyouli) in the primary and secondary prevention of chemotherapy-induced neutropenia in patients with lymphoma. Methods: This single-center, one-arm and open-label clinical study enrolled 119 patients with lymphoma in Peking University Cancer Hospital &amp; Institute from May 2016 to December 2018. Patients ≥45 kg received a single dose of PEG-rhG-CSF for 6mg, &lt; 45kg for 3mg, subcutaneous injection once in 24-48 h after chemotherapy. Results: 119 lymphoma patients, including 60 primary and 59 secondary prevention patients, underwent a total of 427 cycles of chemotherapy. The overall incidence of febrile neutropenia (FN) was 6.32% (27/427), with rates of 5.39% and 7.17% in the primary and secondary prevention groups, respectively. There was no significant difference between two groups ( P&gt; 0.05).The incidence of FN was significantly lower in the second cycle than in the first cycle in both the primary and secondary prevention groups ( In the primary group: cycle 1 vs. cycle 2: 15.00% vs. 2.22%, respectively, P= 0.027; In the secondary group: cycle 1 vs. cycle 2: 16.95% vs. 5.08%, respectively, P= 0.040). The overall incidence of grade Ⅳ neutropenia was 13.58% (58/427), with rates of 8.82% and 17.94% in the primary and secondary prevention groups, respectively. There was a significant difference between two groups ( P= 0.006). The incidence of grade Ⅳ neutropenia was significantly lower in the second cycle than in the first cycle (In the primary group: cycle 1 vs. cycle 2: 25.00% vs. 4.44%, respectively, P= 0.005; In the secondary group: cycle 1 vs. cycle 2: 47.46% vs. 11.86%, respectively, P&lt; 0.001). The main treatment-related adverse event was bone pain, with an incidence of 2.52% (3/119). Conclusions: PEG-rhG-CSF can effectively reduce the incidence of FN and neutropenia with good safety in patients with lymphoma after chemotherapy. Primary prevention can significantly reduce the risk of grade IV neutropenia in all chemotherapy cycles compared with the secondary prevention. Clinical trial information: NCT02905916 .

Efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor in the prevention of chemotherapy-induced neutropenia in patients with breast cancer.

e12515 Background: To explore the efficacy and safety of pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, brand name: Jinyouli) in the prevention of neutropenia in breast cancer patients receiving adjuvant chemotherapy with EC regimen (epirubicin combined with cyclophosphamide). Methods: Retrospective analysis was conducted on breast cancer patients receiving adjuvant chemotherapy with EC regimen in Hengshui People's Hospital between January 2018 to October 2019. In cycle 1, all patients developed grade 3/4 neutropenia and PEG-rhG-CSF was used prophylactically in the subsequent cycles. The incidence of grade 3/4 neutropenia, febrile neutropenia (FN), chemotherapy delay and dose adjustment were observed as well as relative dose intensity (RDI), antibiotics application and adverse events. Results: 96 breast cancer patients were enrolled and all of them developed grade 3/4 neutropenia (100%) in cycle 1. After secondary prophylactic use of PEG-rhG-CSF, the incidence of grade 3/4 neutropenia decreased to 26.32% (25/95), 12.50% (10/80) and 13.63% (9/66) in cycle 2-4, respectively, with a statistically significant difference with cycle 1 ( P&lt;0.001); The incidence of FN decreased from 2.08% (2/96) in cycle 1 to 0% (0/95), 1.25% (1/80) and 0% (0/66) in the subsequent cycles ( P&gt;0.05). The incidence of chemotherapy delay was 2.08% (2/96), 2.50% (2/80) and 1.52% (1/66) in cycle 2-4, respectively, and the incidence of dose adjustment was 9.38% (9/96) in cycle 2. There was no dose adjustment in cycle 3-4. The average RDI was 92%, 92% and 94% in cycle 2-4, respectively. The most common treatment-related adverse events were fever (2.08%), muscle pain (1.04%) and fatigue (1.04%). Conclusions: PEG-rhG-CSF secondary prevention can effectively reduce the incidence of neutropenia in breast cancer patients receiving adjuvant chemotherapy with EC regimen, which ensures the implementation of standard-dose chemotherapy with good safety.

Pegfilgrastim (PEG-G-CSF) induces anti-PEG IgM in a dose dependent manner and causes the accelerated blood clearance (ABC) phenomenon upon repeated administration in mice

Pegfilgrastimis a recombinant PEGylated human granulocyte colony-stimulating factor (G-CSF) analog filgrastim (trade names Neulasta® or G-Lasta®) that stimulates the production of white blood cells (neutrophils). It is employed as an alternative to filgrastim (G-CSF) for chemotherapy-induced neutropenia in patients due to its longer half-life. In clinical settings, PEG-G-CSF is administered to cancer patients via both the s.c. and i.v. routes. In a murine study, we showed that, regardless of administration route, initial doses of PEG-G-CSF above 0.06 mg/kg elicited anti-PEG immune response in a dose-dependent manner. I.v. administration elicited higher levels of anti-PEG IgM than the s.c. route. Initial doses of PEG-G-CSF (6 mg/kg) that were high enough to trigger production of anti-PEG IgM, did not trigger the accelerated clearance of a lower subsequent dose (0.06 mg/kg) that was similar to i.v. clinical doses of PEG-G-CSF, but when the subsequent dose of PEG-G-CSF was raised to (6 mg/kg), the initial dose triggered the accelerated clearance of the second dose via an anti-PEG IgM-mediated complement activation. Similar observations were noted when an increased PEG-OVA dose was given as the second dose, indicating that pre-existing and/or treatment-induced anti-PEG antibodies might compromise the therapeutic activity and/or reduce tolerance of other PEGylated formulations. To the best of our knowledge, this is the first report to suggest the induction of the ABC phenomenon upon repeated injections of pegfilgrastim. In the clinic, cancer patients, receiving multiple cycles of chemotherapy, receive multiple cycles of pegfilgrastim to avoid infections and substantial morbidity. The ABC phenomenon to pegfilgrastim appears to be the cause of loss of clinical benefit of sequential treatments with pegfilgrastim in patients.

Abstract P2-14-12: Eflapegrastim, a novel long-acting granulocyte-colony stimulating factor: Integrated safety results in patients with early-stage breast cancer treated with TC chemotherapy

Abstract Background: Eflapegrastim (E) represents the first myeloid growth factor innovation in more than 15 years. A novel, long-acting recombinant human granulocyte-colony stimulating factor (rhG-CSF), E consists of a rhG-CSF analog conjugated to a human IgG4 Fc fragment via a polyethylene glycol linker. Preclinical and Phase I and II pharmacodynamic and pharmacokinetic data showed increased potency for E versus pegfilgrastim (P). Two independent randomized Phase III trials comparing fixed dose E and P (E 3.6 mg G-CSF and P 6.0 mg G-CSF) for the management of chemotherapy-induced neutropenia (CIN) have recently been completed. Both trials met the primary endpoint of non-inferiority for E vs P in Cycle 1 duration of severe neutropenia (P&amp;lt;.001). Here we provide an integrated summary of the safety of E administered at a fixed dose in a pre-filled syringe. Patients and Methods: Patients with early-stage breast cancer (ESBC) who were candidates for adjuvant or neoadjuvant chemotherapy were randomized 1:1 in two open-label Phase III trials to E 13.2 mg (3.6 mg G-CSF) or standard P (6 mg G-CSF) administered on Day 2 following TC (docetaxel/cyclophosphamide) chemotherapy on Day 1 of each of 4 cycles. Blood for CBC and serum chemistry was collected in every cycle. Safety assessments began with the first dose of TC and continued for one year after the last dose of study drug. AEs and laboratory values were graded according to NCI CTCAE version 4.03. Immunogenicity was assessed from blood samples collected on Day 1 of each cycle, at the end-of-treatment visit, and at 6- and 12-month follow-up visits. Results: A total of 660 patients who received at least one dose of eflapegrastim (n=334) or pegfilgrastim (n=326) were included in this integrated safety analysis. The two treatment groups were well balanced for demographics and baseline disease characteristics. The mean age was 59y, ~40% were aged &amp;gt;65y, ~54% weighed &amp;gt;75kg, and ~80% were treated in the adjuvant setting. Median relative dose intensity for T and C was &amp;gt;99% for both groups. A similar percentage of patients in both treatment groups discontinued treatment due to AEs (4% E vs 6% P), with 2% in each group discontinuing due to AEs related to E or P. Serious AEs were similar in both groups (15% each). Incidence of AEs irrespective of causality were also similar between groups (74% E vs. 72% P). No notable differences between groups were observed in the types of study-drug-related AEs. The majority of study-drug-related AEs occurred with an incidence ≤10% for both E and P. As expected with myeloid growth factors, study-drug-related AEs occurring in &amp;gt;10% in either group were bone pain (E vs P: 33% vs 34%), arthralgia (15% vs 10%), back pain (14% vs 9%), myalgia (14% vs 9%), and headache (11% vs 8%). Incidence of febrile neutropenia and neutropenic complications were similar and less than 5% in each treatment group. No leukocytosis, splenic rupture, or anaphylaxis was reported in any patient receiving E or P. The overall incidence of immunogenicity was similar in both groups and there was no demonstrable impact on clinical safety or efficacy. Conclusions: Two large, randomized Phase III trials (Total n=660) of E vs P administered once-per-cycle showed E at a lower G-CSF dose to be safe and effective for the prophylaxis of CIN in patients with ESBC receiving TC chemotherapy. E is a novel long-acting rhG-CSF with increased potency and similar toxicity to P and may provide an attractive alternative for growth factor support of patients at high risk for CIN-related complications. Citation Format: Lee S Schwartzberg, Gajanan Bhat, Julio Peguero, Richy Agajanian, Jayaram Bharadwaj, Alvaro Restrepo, Osama Hlalah, Inderjit Mehmi, Shanta Chawla, Francois Lebel, Patrick W Cobb. Eflapegrastim, a novel long-acting granulocyte-colony stimulating factor: Integrated safety results in patients with early-stage breast cancer treated with TC chemotherapy [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P2-14-12.

Prophylaxis of breast cancer chemotherapy for bone marrow toxicity: more individualized and safer.

We thank Dr. Tirelli, Dr. Carbone, Dr. Francia and Dr. Di Francia for the interest they have taken in our paper “Efficacy and safety of mecapegfilgrastim for prophylaxis of chemotherapy-induced neutropenia in patients with breast cancer: a randomized, multicenter, active-controlled phase III trial”, and appreciate their comments (1,2).

A Randomized Controlled Clinical Study of Peg-Rhg-CSF for Preventing Chemotherapy-Induced Neutropenia in Patients with B-Cell Non-Hodgkin Lymphoma

Introduction: B-cell non-Hodgkin lymphoma is the most frequent type of non-Hodgkin's lymphoma. RCHOP regimen is established as the standard therapy for aggressive and indolent B-cell NHL, which has a 10%-20% rate of febrile neutropenia (FN). Recently, pegylated recombinant human granulocyte colony stimulating factor (PEG-rhG-CSF) is frequently used in clinical practice. This randomized controlled clinical study was conducted to investigate the efficacy and safety of prophylactic PEG-rhG-CSF in patients with B-cell non-Hodgkin lymphoma on RCHOP chemotherapy. Methods:We included 162 patients with pathological diagnosis of B-cell non-Hodgkin lymphoma including diffuse large B-cell lymphoma, follicular lymphoma and mantle cell lymphoma (MCL),from October 2016 to May 2019 at Shandong Provincial Hospital Affiliated to Shandong University. All patients gave written informed consent in accordance with the Declaration of Helsinki. The patients were randomized into PEG-rhG-CSF and rhG-CSF groups. Each patient received three cycles of chemotherapy with identical RCHOP regimens. In the study group, the patients received PEG-rhG-CSF 6mg(weight≥45Kg)or 3mg(weight≤45Kg)once 24 hours after the end of chemotherapy drugs of every chemotherapy cycle. In the control group, they weren't preventively administered rhG-CSF. If their neutrophil count (ANC)≤1.0×109/L, they were administered rhG-CSF:5ug/kg/day until their neutrophil count (ANC)≥2.0×109/L. The primary endpoint was the incidence of III/IV grade neutropenia and febrile neutropenia(FN) after each chemotherapy cycle. Meanwhile the rate of antibiotics application and safety were observed. Analyses were performed with SPSS Statistics 20.0 (IBM-SPSS, Chicago, Illinois). The numerical data was presented as mean ± SD. Statistical analysis was performed using one-way analysis of variance and chi-square test. A p-value&lt;0.05 was considered statistically significant. Results: Clinical characteristics for PEG-rhG-CSF and rhG-CSF groups were shown in Table1. There were no significant differences in age, gender,height, body weight, body mass index, Ann Arbor and IPI staging. The incidence of IV grade neutropenia during cycle 1 in 81 evaluable study cycles and 81 evaluable control cycles were 7.41% and 35.80%( P&lt;0.01), with durations of 2.85±0.62 days and 3.11±1.23 days (P&gt;0.05). The differences in I/II/III grade neutropenia between study and control groups weren't statistically significant (Table2,Fig.1). After secondary prophylactic use of PEG-rhG-CSF In the study group, the incidences of III/IV grade neutropenia decreased from 77.78% to 14.81% (P&lt;0.01).Statistically significant differences were observed in the incidences of FN (12.35% and 34.57% for the PEG-rhG-CSF and rhG-CSF groups, respectively; P&lt;0.01) and in the proportion of patients who received antibiotic therapy (11.11% and 37.04%, respectively; P&lt;0.01) during cycle 1(Table2,Fig .2). The safety profiles of PEG-rhG-CSF and rhG-CSF were similar. Bone pain occurred in 7.41% of the cases during the study cycles and 2.47% in the control cycles (P&gt;0.05 ), which were mostly mild or moderate. Patients receiving PEG-rhG-CSF who developed III/IV grade neutropenia were significantly older than those without neutropenia (53.41±14.96 vs. 63.64±4.65;years; p=0.01) (Fig.3).The incidence of III/IV grade neutropenia in patients older than 60 years was significantly higher than that in patients younger than 60 years(24.44% vs. 6.38%; P =0.038). Conclusions: Prophylactic use of PEG-rhG-CSF could effectively reduce the incidences of grade III/IV neutropenia and FN, which ensures that patients with lymphoma receive standard-dose chemotherapy to improve prognosis. III/IV grade neutropenia after prophylactic use of PEG-rhG-CSF were more likely to occur in patients older than 60 years. After the use of PEG-rhG-CSF, the elderly patients should be pay more attention to them. Disclosures No relevant conflicts of interest to declare.