Etoposide combined with cytarabine and pegfilgrastim for poorly mobilizing patients with multiple myeloma and lymphoma: A prospective multicentre study.

A chemotherapy-based mobilization regimen in patients who mobilize poorly, based on etoposide, cytarabine and pegfilgrastim (EAP), has recently been introduced. The aim of this prospective study was to investigate the efficacy and safety of the EAP regimen in patients with poorly mobilizing multiple myeloma (MM) or lymphoma. This single-arm clinical trial was performed at eight public hospitals in China and was registered as a clinical trial (NCT05510089). The inclusion criteria were; (1) diagnosis of MM or lymphoma, (2) defined as a 'poor mobilizer' and (3) aged 18-75 years. The EAP regimen consisted of etoposide 75 mg/m2/day on days 1-2, cytarabine 300 mg/m2 every 12 h on days 1-2 and pegfilgrastim 6 mg on day 6. The primary endpoint of the study was the ratio of patients achieving adequate mobilization (≥2.0 × 106 CD34+ cells/kg). From 1 September 2022 to 15 August 2023, a total of 58 patients were enrolled, 53 (91.4%) achieved adequate mobilization, while 41 (70.7%) achieved optimal mobilization with a median number of cumulative collected CD34+ cells was 9.2 (range 2.1-92.7) × 106/kg and the median number of apheresis per patient of 1.2. The median time from administration of the EAP regimen to the first apheresis was 12 days. Approximately 8.6% of patients required plerixa for rescue, which was successful. Twelve (20.7%) of the 58 patients suffered grade 2-3 infections, while 25 (43.1%) required platelet transfusions. The duration of neutrophil and platelet engraftment was 11 days. In conclusion, these results suggest that the EAP mobilization regimen might be a promising option for poorly mobilizing patients with MM or lymphoma.

Efficacy and safety of biosimilar Peg-filgrastim after autologous stem cell transplant in myeloma and lymphoma patients: a comparative study with biosimilar Filgrastim, Lenograstim, and originator Peg-filgrastim.

Data about biosimilar Peg-filgrastim (bioPEG) in autologous stem cell transplant (ASCT) are still scarce. The aim of this study has been to assess efficacy and safety of bioPEG among lymphoma and myeloma patients undergoing ASCT, comparing these data with historical controls receiving other G-CSFs. Furthermore, an economic evaluation has been included to estimate the savings by using bioPEG. This is a prospective cohort study comparing lymphoma and myeloma patients undergoing ASCT and receiving bioPEG (n = 73) with three historical consecutive cohorts collected retrospectively who received other G-CSFs (Lenograstim - Leno - n = 101, biosimilar Filgrastim - bioFIL n = 392, and originator Peg-filgrastim - oriPEG n = 60). We observed a significantly shorter time to neutrophils and platelet engraftment (p < 0.001) in patients treated with bioPEG and oriPEG. Moreover, patients who received bioPEG showed a shorter hospitalization time (p < 0.001) and a lower transfusion need (p < 0.001). We did not observe any significant difference in terms of transplant-related mortality, mucositis, and diarrhea among the four groups. No serious adverse events were associated with bioPEG. Similar data were obtained after running a stratified analysis for lymphomas and myeloma separately conducted by using a propensity score matching. The average total cost per patient of bioPEG was € 18218.9 compared to € 23707.8, € 20677.3 and € 19754.9 of Leno, oriPEG, and bioFIL, respectively. In conclusion, bioPEG seems to be as effective as the originator and more effective than short-acting G-CSFs in terms of post-transplant engraftment in myeloma and lymphoma patients undergoing ASCT. Moreover, bioPEG was cost-effective when compared with the other G-CSFs.

Achieving white blood cell equity: are the safety profiles of biosimilar and reference pegfilgrastims comparable?

Biosimilars can provide choices for patients and may provide cost savings; however, their uptake has been slow in the USA, in part due to limited knowledge. To provide additional confidence in US pegfilgrastim biosimilars, this narrative review compared the safety profiles of biosimilar pegfilgrastims, currently approved or filed for approval in the USA, with the EU- and US-approved reference pegfilgrastims. Headache and bone pain were common to biosimilars and reference products and occurred at a similar incidence. Clinical trial data on the safety profiles of biosimilar pegfilgrastims and reference products have demonstrated similarity and comparability, with no unexpected safety outcomes. Overall, the safety profiles of biosimilar pegfilgrastims and reference pegfilgrastims demonstrated a high degree of similarity and comparability.

Pegfilgrastim is a biologic drug (one made in living cells such as bacteria) that is given to some patients being treated for cancer. Pegfilgrastim is prescribed to reduce a patient's risk of infection due to a weakened immune system caused by various chemotherapy treatment plans. A biosimilar is a type of biologic medicine that is highly similar to a US FDA-approved reference biologic, and is often cheaper, making it more widely available to patients. As of March 2023, there are eight pegfilgrastim biosimilars (six approved and two awaiting approval by the FDA). This review compared the side effects for the reference pegfilgrastim with the biosimilar pegfilgrastims. The side effects in general and the side effects from treatment were similar for the reference pegfilgrastim and for the biosimilar pegfilgrastims, with the most common side effects being headache and bone pain. Serious side effects such as allergic reactions or problems with the spleen were very low and were also similar between the reference pegfilgrastim and the biosimilar pegfilgrastims. These results show that the safety of the biosimilar pegfilgrastims was similar to the reference pegfilgrastim, with no unexpected side effects. With comparable safety to their reference product, biosimilars have the potential to improve patient access to more affordable treatment options.

Efficacy of delayed pegfilgrastim administration following consolidation therapy with high-dose cytarabine (HiDAC) in acute myeloid leukemia (AML) patients.

PURPOSE: To study the effects of delaying pegfilgrastim administration following high-dose cytarabine (HiDAC) consolidation in AML patients on time to neutrophil count recovery, infectious complications, and survival. METHODS: Single-center retrospective chart review of 55 patients receiving pegfilgrastim as early administration (within 72 h) or delayed administration (after 72 h) of HiDAC. RESULTS: The difference in neutrophil recovery time was similar between the early and delayed groups (18 days versus 19 days, p < 0.28). Infections were seen in four patients in the early administration group following chemotherapy compared to none in the delayed group (p = 0.04). Febrile neutropenia rates were also decreased in the delayed administration group (23.1% versus 10.3%, p = 0.28) as well as a trend towards longer median survival (16 months versus 19 months, p = 0.69) and overall survival (21 months versus 31 months, p = 0.47). CONCLUSION: A difference in time to neutrophil recovery was not observed between the early and delayed administration groups yet decreased infectious complications may support the delayed administration of pegfilgrastim in these patients.

Filgrastim-induced hemophagocytic lymphohistiocytosis in a patient with mantle cell lymphoma: A case report.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disease potentially induced by various causes. Very few reports have described HLH induced by granulocyte colony-stimulating factor (G-CSF) and those few previous reports have uniformly indicated that continuing G-CSF is unfeasible once HLH has been induced. A 52-year-old Japanese man who had been diagnosed with mantle cell lymphoma with systemic and central nervous system involvements received rituximab, hyper-fractionated cyclophosphamide, vincristine, Adriamycin and dexamethasone (R-HCVAD)/methotrexate and cytarabine. During the second cycle of R-HCVAD, the patient developed severe back pain, thrombocytopenia, elevated serum lactate dehydrogenase and ferritin levels, and hemophagocytosis in the bone marrow. Complete remission (CR) of mantle cell lymphoma was confirmed on whole-body computed tomography, brain magnetic resonance imaging, and bone marrow biopsy. The patient was diagnosed with HLH induced by filgrastim. HLH recovered with intravenous methylprednisolone at 1 g/day for 3 days, followed by oral prednisolone tapered off over 5 days. The patient continued chemotherapy with a change in the G-CSF formulation from filgrastim to lenograstim and prophylactic administration of corticosteroids. He safely completed scheduled chemotherapy without recurrence of HLH and successfully maintained CR of lymphoma. Although rare, G-CSF potentially induces HLH. Changing the G-CSF formulation and steroid prophylaxis may allow safe continuation of G-CSF.

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.

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

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

BACKGROUND: Neoadjuvant docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy is a new standard for locally advanced esophageal squamous cell carcinoma. The optimal timing of pegfilgrastim with the DCF regimen to prevent febrile neutropenia (FN) remains controversial. The effectiveness of concomitant pegfilgrastim administration with continuous 5-fluorouracil (5-FU) infusion in the DCF regimen was therefore assessed. METHODS: All patients who received neoadjuvant DCF for esophageal cancer were retrospectively assessed. Patients who had been scheduled to receive pegfilgrastim on days 3-5 (early group) or days 7-9 (regular group) of the DCF regimen were included. Uni- and multivariate analyses were used to assess risk factors for FN. RESULTS: Eighty-eight patients were included in the analysis. The 26 patients in the early group received pegfilgrastim as scheduled. In the 62 patients of the regular group, 51 received pegfilgrastim at a median of 7 days after starting DCF chemotherapy. However, 11 patients in the regular group could not receive pegfilgrastim. Twenty-two patients of the regular group and 2 patients of the early group developed FN after the first session of DCF. Early administration of pegfilgrastim and grade 4 neutropenia were significantly associated with onset of FN, with multivariate analysis identifying early administration of pegfilgrastim as an independent preventive factor and grade 4 neutropenia as a risk factor, after adjusting for sex and age. CONCLUSION: Early pegfilgrastim administration is a safe approach that reduces the incidence of FN in DCF therapy. Using pegfilgrastim with continuous 5-FU infusion in the DCF regimen represents a reasonable option to prevent FN.

CD34+ cell yield among healthy donors: Large-scale model development and validation.

BACKGROUND: Successful engraftment in hematopoietic stem cell transplantation necessitates the collection of an adequate dose of CD34+ cells. Thus, the precise estimation of CD34+ cells harvested via apheresis is critical. Current CD34+ cell yield prediction models have limited reproducibility. This study aims to develop a more reliable and universally applicable model by utilizing a large dataset, enhancing yield predictions, optimizing the collection process, and improving clinical outcomes. MATERIALS AND METHODS: A secondary analysis was conducted using the Center for International Blood and Marrow Transplant Research database, involving data from over 17 000 healthy donors who underwent filgrastim-mobilized hematopoietic progenitor cell apheresis. Linear regression, gradient boosting regressor, and logistic regression classification models were employed to predict CD34+ cell yield. RESULTS: Key predictors identified include pre-apheresis CD34+ cell count, weight, age, sex, and blood volume processed. The linear regression model achieved a coefficient of determination (R2) value of 0.66 and a correlation coefficient (r) of 0.81. The gradient boosting regressor model demonstrated marginally improved results with an R2 value of 0.67 and an r value of 0.82. The logistic regression classification model achieved a predictive accuracy of 96% at the 200 × 106 CD34+ cell count threshold. At thresholds of 400, 600, 800, and 1000 × 106 CD34+ cell count, the accuracies were 88%, 83%, 83%, and 88%, respectively. The model demonstrated a high area under the receiver operator curve scores ranging from 0.90 to 0.93. CONCLUSION: This study introduces advanced predictive models for estimating CD34+ cell yield, with the logistic regression classification model demonstrating remarkable accuracy and practical utility.

Effect of Loratadine for Pegfilgrastim-Induced Bone Pain.

AIMS: Breast cancer patients on chemotherapy who receive pegfilgrastim to prevent neutropenia may experience severe bone pain as a side effect. Traditional treatment recommendations include nonsteroidal anti-inflammatory drugs (NSAIDs), acetaminophen, opioids, and/or antihistamine use. However, little research was found comparing these interventions. The study aim was to address the gaps in literature and to explore the use of and perceived effectiveness of loratadine versus acetaminophen or NSAIDs in women with breast cancer treated with pegfilgrastim. This study also sought to understand how patients became aware of loratadine or other treatments for management of bone pain. DESIGN/METHODS: This cross-sectional study used survey methods to collect data from 66 adult female breast cancer patients receiving chemotherapy with pegfilgrastim. RESULTS: The incidence of bone pain was 45% (n = 30) in our sample, but more than half (n = 45; 69%) of the women took either acetaminophen, NSAIDs, or loratadine alone or in combination to prevent bone pain. All medication were rated as effective by patients, with acetaminophen slightly more effective than loratadine, and loratadine more effective than NSAIDs. CONCLUSIONS: Acetaminophen, NSAIDs, and loratadine are easily available and inexpensive. However, unlike acetaminophen and NSAIDs, loratadine is dosed once a day and well tolerated with minimal adverse effects. CLINICAL IMPLICATIONS: Randomized controlled trials are needed to adequately assess the effectiveness of all three medication options. Because little is known about optimal use of any of these medications for pegfilgrastim-induced bone pain, it is also important to identify the optimal time to initiate treatment and ideal treatment duration.

Filgrastim Use in the Treatment of Azathioprine-Induced Myelosuppression Toxicity After Prescription Error in the Feline.

Only one report on the successful use of filgrastim (granulocyte colony-stimulating factor) in cats for severe neutropenia following azathioprine toxicity exists. Here, we report on a case in which a cat was prescribed methimazole but the medication was filled incorrectly with azathioprine tablets and the prescription label indicated a methimazole dosing regimen that was administered for three days before recognition of the error. On presentation, the cat's physical examinations were consistent with previous examinations before ingestion of azathioprine. A complete blood cell count revealed neutropenia and leukopenia. The cat later developed hyporexia, dehydration, and vomiting. Treatment included antinausea and appetite stimulant medications, filgrastim, and antibiotics. Filgrastim given as subcutaneous injections over the course of treatment increased neutrophil cell counts after suppression. The cat made a full recovery after responding to the treatment protocol. Based on the perceived response to filgrastim in this single feline case report, its use can be considered for the treatment of azathioprine-induced neutropenia in cats.

[Timing of Administration of Pegfilgrastim and Prophylaxis for Febrile Neutropenia for Patients with Early Breast Cancer Receiving Chemotherapy].

Febrile neutropenia(FN)causes a prolonged treatment schedule and decreased relative dose intensity(RDI)during cancer chemotherapy, which adversely affects prognosis. In recent years, dose-dense(dd)chemotherapy has been used as adjuvant chemotherapy for patients with breast cancer based on the results of improved disease-free survival according to meta-analysis data. Regarding neoadjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer, taxanes and trastuzumab with the addition of pertuzumab have shown higher pathological complete response rates and elevated incidences of FN. One hundred seventy-six patients received pegfilgrastim(PEG)prophylaxis between January 2011 and January 2023. Until 2019, the median day of PEG prophylaxis was day 4 from chemotherapy completion(days 2- 3, 14 cases; day 4, 41 cases; and day 5, 8 cases)with antibiotic prophylaxis in 58 patients(92%). FN was observed in 19 cases(30%). The RDIs of TC and FEC were 96.8% and 96.0%, respectively. Meanwhile, the median day of PEG prophylaxis after 2020 was day 2 from chemotherapy completion(days 2-3, 108 cases; day 4, 4 cases; and day 5, 1 case)without antibiotic prophylaxis. FN was not observed in any of the cases. The RDI of all regimens was 99.7%. Although there were some differences in chemotherapy regimens, an earlier timing of PEG prophylaxis(especially 24-48 hours from chemotherapy completion)has been shown to reduce the incidence of FN and increase the RDI.

The Impact of HIV Infection on Neoadjuvant and Adjuvant Chemotherapy Relative Dose Intensity in South African Patients with Breast Cancer.

INTRODUCTION: In the South African Breast Cancer and HIV Outcomes (SABCHO) study, we previously found that breast cancer patients living with HIV and treated with neoadjuvant chemotherapy achieve lower rates of complete pathologic response than patients without HIV. We now assess the impact of comorbid HIV on receipt of timely and complete neoadjuvant and adjuvant chemotherapy. MATERIALS AND METHODS: Since June 2015, the SABCHO study has collected data on women diagnosed with breast cancer at 6 South African hospitals. We selected a sample of participants with stages I-III cancer who received ≥2 doses of neoadjuvant or adjuvant chemotherapy. Data on chemotherapies prescribed and received, filgrastim receipt, and laboratory values measured during treatment were captured from patients' medical records. We calculated the mean relative dose intensity (RDI) for all prescribed chemotherapies. We tested for association between full regimen RDI and HIV status, using linear regression to control for demographic and clinical covariates, and for association of HIV with laboratory abnormalities. RESULTS: The 166 participants living with HIV and 159 without HIV did not differ in median chemotherapy RDI: 0.89 (interquartile range (IQR) 0.77-0.95) among those living with HIV and 0.87 (IQR 0.77-0.94) among women without HIV. Patients living with HIV experienced more grade 3+ anemia and leukopenia than those without HIV (anemia: 10.8% vs. 1.9%, P = .001; leukopenia: 8.4% vs. 1.9%, P = .008) and were more likely to receive filgrastim (24.7% vs. 10.7%, P = .001). CONCLUSIONS: HIV status did not impact neoadjuvant or adjuvant chemotherapy RDI, although patients with breast cancer living with HIV experienced more myelotoxicity during treatment.

Real-world data analysis of perioperative chemotherapy patterns, G-CSF use, and FN status in patients with early breast cancer.

PURPOSE: This study aimed to describe perioperative chemotherapy patterns, granulocyte colony-stimulating factor (G-CSF) use, and febrile neutropenia (FN) status in patients with early breast cancer (EBC) using real-world data in Japan. METHODS: This retrospective observational study used anonymized claims data. The included patients were ≥ 18 years old, were female, and had breast cancer diagnosis and surgery records between January 2010 and April 2020. Measures included perioperative chemotherapy, G-CSF use (daily and primary prophylaxis [PP]), and FN and FN-related hospitalization (FNH), all examined annually. Perioperative chemotherapy was examined separately for human epidermal growth factor receptor 2-positive/negative (HER2±). A multivariate logistic regression was used to explore the factors associated with FNH. RESULTS: Of 32,597 patients, those with HER2 + EBC treated with anthracycline-based regimens followed by taxane + trastuzumab + pertuzumab increased since 2018, and those with HER2 - EBC treated with doxorubicin/epirubicin + cyclophosphamide followed by taxane and dose-dense regimens increased after 2014. The proportion of patients prescribed daily G-CSF declined after 2014, whereas that of pegfilgrastim PP increased. The incidence proportion of FN remained at approximately 24-31% from 2010 to 2020, while that of FNH declined from 14.5 to 4.0%. The odds of FNH were higher in those aged ≥ 65 years and lower with pegfilgrastim PP administration. CONCLUSION: Despite the increasing use of escalated regimens in the last 5-6 years, FNH continuously declined, and the odds of FNH were lower among patients treated with pegfilgrastim PP. These results may suggest the contribution of PP in part to suppressing FNH levels over the last 5-6 years.

The impact of new and emerging agents on outcomes for febrile neutropenia: addressing clinical gaps.

PURPOSE OF REVIEW: While chemotherapy treatment options for patients with solid and hematologic malignancies have dramatically improved over recent years, chemotherapy-induced neutropenia (CIN) and febrile neutropenia (FN) remain major barriers to delivering treatment at full doses and optimal timing. Despite concurrent advances in granulocyte colony-stimulating factor (G-CSF) administration, multiple barriers to the administration of and disparities in the access to these agents remain. The introduction of new, emerging agents, including biosimilars and novel therapies show promise in improving outcomes for CIN. RECENT FINDINGS: The introduction of biosimilar filgrastim products has improved access to G-CSF administration by driving marketplace competition and has reduced costs for both patients and healthcare systems without sacrificing efficacy. Emerging therapies to address similar issues include long-acting G-CSF products, efbemalenograstim alfa and eflapegrastin-xnst, as well as agents with novel mechanisms of action, plinabulin and trilaciclib. These agents have shown efficacy and cost-saving benefits in certain populations and disease groups. SUMMARY: Multiple emerging agents show promise in decreasing the burden of CIN. Use of these therapies will reduce access disparities and will improve outcomes for patients with cancer receiving cytotoxic chemotherapy. Many ongoing trials are underway to evaluate the roles of these agents for more widespread use.

An observational study of dose dense chemotherapy with lipegfilgrastim support in early breast cancer.

PURPOSE: Breast cancer is one of the most prevalent malignant diseases in women. The development of dose dense chemotherapy regimens has improved clinical outcomes but has been associated with increased hematological toxicity. Currently there is a paucity of data on the use of lipegfilgrastim in dose dense AC treatment in early breast cancer. The purpose of this study was to assess the use of lipegfilgrastim in the treatment of early breast cancer and to examine the incidence of treatment-related neutropenia during the dose dense AC phase and subsequent paclitaxel treatment. METHODS: This was a single arm, non-interventional, prospective study. The primary endpoint was to determine the rate of neutropenia defined as ANC of < 1.0 × 109/L, during four cycles of dose dense AC with lipegfilgrastim support. The secondary endpoints were the incidence of febrile neutropenia, (temperature > 38 °C and ANC < 1.0 × 109/L), treatment delays, premature treatment cessation and toxicity. RESULTS: Forty-one participants were included in the study. Of the 160 planned dose dense AC treatments, 157 were administered, and 95% (152/160) of these were given on time. The rate of treatment delay was 5% (95% CI 2.2 to 9.9%) due to infection (4) and mucositis (1). Four (10%) patients developed febrile neutropenia. The most frequently occurring adverse event was grade 1 bone pain. CONCLUSION: Lipegfilgrastim is an effective option in the prophylaxis of chemotherapy-induced neutropenia, and its use in everyday anti-cancer treatment can be considered.

Effectiveness of biosimilar pegfilgrastim in patients with multiple myeloma after high-dose melphalan and autologous stem cell transplantation.

Multiple myeloma (MM) is the main indication for autologous stem cell transplantation (ASCT). Novel supportive therapies (e.g., granulocyte colony-stimulating factor) have significantly improved post-ASCT-related mortality; however, data on biosimilar pegfilgrastim-bmez (BIO/PEG) in this setting is lacking. This prospective cohort study compared Italian patients with MM who received BIO/PEG post-ASCT with data collected retrospectively from historical control groups from the same center who received either filgrastim-sndz (BIO/G-CSF) or pegfilgrastim (PEG; originator). The primary endpoint was time to neutrophil engraftment (three consecutive days with an absolute neutrophil count ≥ 0.5 × 109/L). Secondary endpoints included incidence and duration of febrile neutropenia (FN). Of the 231 patients included, 73 were treated with PEG, 102 with BIO/G-CSF, and 56 with BIO/PEG. Median age was 60 years and 57.1% were male. Neutrophil engraftment was reached after a median of 10 days in the BIO/PEG and PEG groups and 11 days in the BIO/G-CSF group. Among patients who achieved neutrophil engraftment earlier than this (i.e., day 9), 58% (29/50) were on PEG; of those who achieved it later (i.e., day 11), 80.8% (59/73) were on BIO/G-CSF. FN incidence was higher with BIO/G-CSF (61.4%) versus PEG (52.1%) or BIO/PEG (37.5%) (p = 0.02 among groups). Patients on BIO/PEG had less frequent grade 2-3 diarrhea (5.5%) compared with BIO/G-CSF (22.5%) or PEG (21.9%); grade 2-3 mucositis was most frequent in the BIO/G-CSF group. In conclusion, pegfilgrastim and its biosimilar displayed an advantageous efficacy and safety profile compared with biosimilar filgrastim in patients with MM post-ASCT.

Fosfomycin-induced agranulocytosis: a case report and review of the literature.

BACKGROUND: The intravenous form of fosfomycin, a bactericide antibiotic used to treat multiresistant bacterial infections is little prescribed. The most common reported adverse effects are hypokaliemia and hypernatremia. We describe a case of agranulocytosis, a rarely described side effect that may be fatal. CASE PRESENTATION: A 45 year-old woman was admitted to the intensive care unit for post-surgical meningitis following meningioma resection. Meropenem and vancomycin were first introduced. A DRESS-syndrom with meropenem was suspected. Neutropenia was diagnosed three days after the introduction of parenteral fosfomycin and agranulocytosis four days later. Eosinophilia was also observed. A bone marrow aspiration was performed showing a disappearance of the neutrophil granulocyte line and a significant eosinophilia. Meropenem was discontinued. Fosfomycin was maintained and filgrastim was added. As filgrastim had no effect, the relationship with fosfomycin was suspected, so it was then withheld. An increase of the neutrophil count was observed. Because of the complexity of the case, the unfavorable course of the illness and the urgent need for revision surgery, a rechallenge with fosfomycin was done followed by a decrease of the neutrophil count. CONCLUSION: This is the third paper reporting agranulocytosis induced by fosfomycin, and the first detailed description of a case. Based on chronological and semiological criteria and bibliographic data, the event was qualified as probable with the Naranjo adverse drug probability scale. Literature data is scarce. The summary of product characteristics mentions that only a few cases of transient neutropenia and agranulocytosis have been reported. An analysis of the FDA Adverse Event Reporting System Database highlighted a higher than expected frequency of agranulocytosis in patients treated with fosfomycin. Parenteral fosfomycin is often used in patients receiving other medications, so that it is rarely the only suspect. In our case, the results of the bone marrow aspiration, the sudden drop of the neutrophil count with concomitant eosinophilia and the absence of improvement despite the dose decrease, point towards an immuno-allergic mechanism. However, the overlap between the suspected DRESS induced by meropenem and the agranulocytosis do not allow to conclude with certainty on the causality. Awareness should be raised about this side effect.

Cost-effectiveness of granulocyte colony-stimulating factors (G-CSFs) for the prevention of febrile neutropenia (FN) in patients with cancer.

PURPOSE: Clinical practice guidelines recommend the use of all approved granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, as primary febrile neutropenia (FN) prophylaxis in patients receiving high- or intermediate-risk regimens (in those with additional patient risk factors). Previous studies have examined G-CSF cost-effectiveness by cancer type in patients with a high baseline risk of FN. This study evaluated patients with breast cancer (BC), non-small cell lung cancer (NSCLC), or non-Hodgkin's lymphoma (NHL) receiving therapy who were at intermediate risk for FN and compared primary prophylaxis (PP) and secondary prophylaxis (SP) using biosimilar filgrastim or biosimilar pegfilgrastim in Austria, France, and Germany. METHODS: A Markov cycle tree-based model was constructed to evaluate PP versus SP in patients with BC, NSCLC, or NHL receiving therapy over a lifetime horizon. Cost-effectiveness was evaluated over a range of willingness-to-pay (WTP) thresholds for incremental cost per quality-adjusted life year (QALY) gained. Sensitivity analyses evaluated uncertainty. RESULTS: Results demonstrated that using biosimilar filgrastim as PP compared to SP resulted in incremental cost-effectiveness ratios (ICERs) well below the most commonly accepted WTP threshold of €30,000. Across all three countries, PP in NSCLC had the lowest cost per QALY, and in France, PP was both cheaper and more effective than SP. Similar results were found using biosimilar pegfilgrastim, with ICERs generally higher than those for filgrastim. CONCLUSIONS: Biosimilar filgrastim and pegfilgrastim as primary prophylaxis are cost-effective approaches to avoid FN events in patients with BC, NSCLC, or NHL at intermediate risk for FN in Austria, France, and Germany.

Factors associated with thrombocytopenia in patients treated with pegfilgrastim.

OBJECTIVES: Pegfilgrastim is a long-acting, granulocyte colony-stimulating factor approved in Japan for the prevention of neutropenia caused by antineoplastic agents. Severe thrombocytopenia was reported with pegfilgrastim, however, the factors associated with thrombocytopenia are unclear. This study aimed to explore the factors associated with thrombocytopenia in patients with metastatic castration-resistant prostate cancer treated with pegfilgrastim for primary prophylaxis of febrile neutropenia (FN) with cabazitaxel. MATERIALS AND METHODS: This study included metastatic castration-resistant prostate cancer patients who received pegfilgrastim for primary prophylaxis of FN with cabazitaxel. The timing and severity of thrombocytopenia and factors associated with the reduction rate of platelets were examined in patients who received pegfilgrastim for the primary prevention of FN during the first course of cabazitaxel and by multiple regression analysis. RESULTS: Thrombocytopenia was most common within 7 days of pegfilgrastim administration, with 32 cases of grade 1 and 6 cases of grade 2 as per the Common Terminology Criteria for Adverse Events version 5.0. Multiple regression analysis revealed that the reduction rate of platelets after pegfilgrastim administration was significantly positively correlated with monocytes. In contrast, the presence of liver metastases and neutrophils was significantly negatively correlated with the reduction rate of platelets. CONCLUSION: Thrombocytopenia due to pegfilgrastim administered as primary prophylaxis for FN with cabazitaxel was most likely to occur within one week after pegfilgrastim administration, suggesting that monocytes, neutrophils, and liver metastases were associated with a reduction in platelets.

Cost comparison of filgrastim versus pegfilgrastim and pegfilgrastim biosimilars for inpatient prophylaxis of febrile neutropenia.

INTRODUCTION: The Ohio State University Comprehensive Cancer Center (The James) uses daily subcutaneous filgrastim as the inpatient granulocyte colony-stimulating factor of choice. The coordination of care associated with filgrastim can often be a barrier to patient discharge. The purpose of this study was to compare the inpatient cost of daily filgrastim to single dose pegfilgrastim and biosimilars. METHODS: Adult patients admitted to The James who received at least one dose of filgrastim between June 1, 2021 and August 31, 2021 were retrospectively identified. This study compared the inpatient cost of filgrastim and biosimilars associated with one chemotherapy cycle to the potential inpatient cost of pegfilgrastim and biosimilars based on average sales price (ASP). Additionally, the number and duration of discharge prescriptions for filgrastim was determined. RESULTS: Of the 44 unique patient encounters that met inclusion criteria, 19 received 300-mcg doses of filgrastim and 25 received 480-mcg doses. The median number of doses administered per admission was eight. If each of these patients were to instead receive the most inexpensive biosimilar, pegfilgrastim reference product, the cost would be 216% higher than with filgrastim-sndz. At discharge, 15 patients (34%) received a prescription for filgrastim to be continued for a median duration of 6 days. CONCLUSION: Based on ASP, pegfilgrastim was more costly than filgrastim. Potential rebates and negotiation power may alter the financial outlook of adding pegfilgrastim to inpatient formulary. Exploration of delays in discharge due to insurance coordination for filgrastim continuation in the outpatient setting may also impact formulary decisions.