Aortitis after switching short-acting granulocyte colony-stimulating factors in a lymphoma patient with HLA-B52.

Aortitis is a rare adverse event of granulocyte colony-stimulating factor (G-CSF) treatment. Several previous studies have described recurrent aortitis caused by re-administration of the same G-CSF. However, no previous studies have examined the safety of switching between short-acting G-CSFs in patients who develop aortitis. We report the case of a 55-year-old man with refractory diffuse large B-cell lymphoma, who developed G-CSF-associated aortitis. The aortitis was triggered by filgrastim and recurred after treatment with lenograstim. The patient possessed human leukocyte antigen B52, which has been implicated in Takayasu arteritis. In addition, a drug-induced lymphocyte stimulation test for lenograstim performed upon detection of recurrent G-CSF-associated aortitis produced a positive result. Our case suggests that switching from one short-acting G-CSF to another does not prevent recurrence of G-CSF-associated aortitis. Although the etiology of G-CSF-associated aortitis has not been fully elucidated, our case also suggests that some patients may be genetically predisposed to aortitis.

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.

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.

Half Dose Pegfilgrastim for Patients With Breast Cancer During Chemotherapy: A Case-series.

BACKGROUND/AIM: This study aimed to show the trend of neutrophil counts and frequency of febrile neutropenia after changing pegfilgrastim from 3.6 mg to 1.8 mg. PATIENTS AND METHODS: This case-series study was performed between April 2016 and December 2021 at Hyogo Prefectural Amagasaki General Medical Center. All patients who reduced their normal dose of 3.6 mg pegfilgrastim to 1.8 mg due to adverse events or markedly elevated neutrophil counts were included. Any type of chemotherapy was acceptable. Patients who dropped out within 1 month of receiving 1.8 mg pegfilgrastim were excluded. The primary outcome was the neutrophil counts after receiving 1.8 mg pegfilgrastim. The secondary outcome was febrile neutropenia, which was evaluated by the Common Terminology Criteria for Adverse Events v5.0. RESULTS: The study included seven patients who used a regimen of dose-dense epirubicin and cyclophosphamide, trastuzumab, pertuzumab, and docetaxel, docetaxel, or docetaxel and cyclophosphamide. After using 1.8 mg pegfilgrastim, neutrophil counts changed from a mean of 18,944 [standard deviation (SD)=-7,768] to only 4,447 (SD=1,224). The patients experienced grades 1 to 3 adverse events during the use of 1.8 mg and 3.6 mg pegfilgrastim doses, including febrile neutropenia, and pain. Four patients (57%) complained of grade 1 or 2 fatigue and anorexia. After switching from 3.6 mg pegfilgrastim to 1.8 mg, three patients (42%) experienced adverse events. CONCLUSION: In patients who experienced adverse events due to markedly elevated neutrophil counts with pegfilgrastim, reducing the dose of pegfilgrastim by half may reduce adverse events.

Pharmacokinetic and Pharmacodynamic Characteristics of Tripegfilgrastim, a Pegylated G-CSF, in Pediatric Patients with Solid Tumors.

A long-acting granulocyte colony-stimulating factor, tripegfilgrastim, was approved in Korea for the prevention of chemotherapy-induced neutropenia in adult patients. In this study, we evaluated the pharmacokinetics, pharmacodynamics, and safety of tripegfilgrastim in pediatric patients. A phase I, open-label, single ascending-dose study was performed in pediatric patients with solid tumors or lymphoma (ClinicalTrials.gov, NCT02963389). The patients were stratified according to age groups (aged 6 to 12 or 12 to 19 years) and received a single subcutaneous dose of tripegfilgrastim 60 µg/kg or 100 µg/kg. Tripegfilgrastim was administered 24 hours after the end of the chemotherapy, and serial blood sampling and safety monitoring were conducted. Twenty-seven patients with solid tumors were enrolled in this study. Tripegfilgrastim was detectable in plasma for an extended period (terminal half-life > 40 hours), and plasma concentrations increased slightly less than dose proportionally. The mean duration of grade 4 neutropenia was reduced as the average tripegfilgrastim concentration during the initial neutrophil recovery process increased. No substantial differences in the pharmacokinetic and pharmacodynamic responses were observed between the two age groups. When stratified by body weight, weighing more than 45 kg has a higher risk of a prolonged neutropenia period when receiving the lower dose (60 µg/kg) of tripegfilgrastim. Tripegfilgrastim was generally safe and well-tolerated in the pediatric patients. These results justify further clinical investigations of tripegfilgrastim at 100 µg/kg dose in pediatric patients.

Association Between Time Since Administration of Pegylated G-CSF (Pegfilgrastim) and Bone Marrow Uptake on FDG PET/CT: Determination of a Minimum Interval.

BACKGROUND. Pegfilgrastim administration after chemotherapy increases bone marrow and spleen FDG uptake. Consensus is lacking regarding the optimal interval between pegfilgrastim administration and FDG PET/CT. OBJECTIVE. The purpose of this study was to assess the association between bone marrow and spleen uptake and the interval between pegfilgrastim administration and FDG PET/CT. METHODS. This retrospective study included 70 oncology patients (mean age, 64 ± 12 [SD] years; 48 men, 22 women) receiving chemotherapy who underwent FDG PET/CT (study scan) within 35 days after pegfilgrastim administration and who underwent additional FDG PET/CT at least 4 months before pegfilgrastim initiation or at least 3 months after last pegfilgrastim administration (reference scan). A nuclear medicine physician recorded the SUVmean for normal osseous structures and spleen and assessed bone marrow uptake using a 4-point visual scale (1, no abnormal uptake; 2, clinically insignificant uptake; 3, clinically significant uptake possibly interfering with interpretation; 4, clinically significant uptake expected to interfere with interpretation). RESULTS. Percentage change in SUVmean between reference and study scans significantly increased (p < .05) as the interval increased for five sites (i.e., for patients with interval of 7-13 vs 29-35 days, mean percentage change was 32.3% ± 18.2% vs 11.5% ± 17.3% for cervical vertebra, 42.2% ± 18.3% vs 21.3% ± 14.2% for thoracic vertebra, 47.2% ± 19.8% vs 19.1% ± 13.9% for lumbar vertebra, 51.1% ± 25.8% vs 12.7% ± 11.3% for pelvis, and 53.0% ± 25.6% vs 4.4% ± 14.1% for lower extremity); percentage change was not associated with the interval for upper extremity or spleen (p > .05). Visual uptake scores of 4, 3, 2, and 1 were observed in days 7-21, 12-22, 12-28, and 14-35, respectively. Percentage of patients with a score of 3 or 4 was 94.4% for days 7-13, 58.1% for days 14-21, 6.7% for days 22-28, and 0% for days 29-35. A total of 71.4% of patients had a score of 3 or 4 on day 7-21, whereas 4.8% had a score of 3 and 0% had a score of 4 on days 22-35. CONCLUSION. A visual uptake score of 3 or 4 was consistently observed throughout an approximately 3-week interval following pegfilgrastim administration, without any such case beyond 22 days. CLINICAL IMPACT. We recommend a preferred interval of at least 3 weeks after pegfilgrastim administration before PET/CT.

Phase I/II study to assess the clinical pharmacology and safety of single ascending and multiple subcutaneous doses of PF-06881894 in women with non-distantly metastatic breast cancer.

PURPOSE: To evaluate the pharmacodynamics (PD), pharmacokinetics (PK), and safety of single and multiple doses of PF-06881894 (pegfilgrastim-apgf; Nyvepria™), a biosimilar to reference pegfilgrastim (Neulasta®), in women with non-distantly metastatic breast cancer. METHODS: In Phase I (Cycle 0) of this Phase I/II study, the PD response (absolute neutrophil count [ANC]; CD34 + count), PK profile, and safety of a single 3- or 6-mg subcutaneous dose of PF-06881894 were assessed in chemotherapy-naïve patients before definitive breast surgery. In Phase II (Cycles 1-4), the PD response (duration of severe neutropenia [DSN, Cycle 1], ANC [Cycles 1 and 4]) and PK profile (Cycles 1 and 4) of single and multiple 6-mg doses of PF-06881894 concomitant with chemotherapy and after definitive breast surgery were assessed. RESULTS: Twenty-five patients (mean age 59 years) were enrolled (Cycle 0, n = 12; Cycles 1-4, n = 13). In Cycle 0, PD responses and PK values were lower with 3-mg versus 6-mg PF-06881894. In Cycles 1 and 4, mean DSN was 0.667 days after single or multiple 6-mg doses of PF-06881894, respectively. In Cycle 4 versus Cycle 1, PD responses were more robust; PK values (mean area under the curve, maximum concentration) were lower; and clearance values were higher. The safety profile of PF-06881894 was similar to that for reference pegfilgrastim. CONCLUSION: PF-06881894 as a single 3- or 6-mg dose prior to definitive surgery, or multiple 6-mg/cycle doses postoperatively, with/without myelosuppressive chemotherapy, was consistent with the clinical pharmacology and safety profile of reference pegfilgrastim. TRIAL REGISTRATION: October 2017. ClinicalTrials.gov Identifier: NCT02650193. EudraCT Number: 2015-002057-35.

Diffuse alveolar hemorrhage in a healthy stem cell donor following administration of granulocyte colony - stimulating factor.

BACKGROUND: Granulocyte colony - stimulating factor (G-CSF) is frequently used in healthy adults prior to stem cell donation in order to mobilize stem cells to peripheral blood. Adverse events of G-CSF occur in about 30% and mainly include bone pain, fatigue, and headache. Pulmonary adverse events are rare. CASE PRESENTATION: Here, we describe a case of a healthy donor who developed diffuse alveolar hemorrhage after G-CSF administration. We suggest the underlying mechanism of this injury. CONCLUSION: Diffuse alveolar hemorrhage can occur following G-CSF administration. Treating physicians should be aware of this infrequent but often life-threatening pulmonary side effect of G-CSF.

G-CSF and G-CSF-related vasculitis: a systematic review of the literature and intriguing future research perspectives.

Background: There are several case reports suggesting that G-CSFs may, in rare conditions, produce serious side effects, such as vasculitis. Materials & methods: A systematic search was conducted in Medline via PubMed, Embase and Cochrane Library to describe this unusual side effect to raise awareness among clinicians for early recognition and treatment. Results: Fifty-seven patients were analyzed. The most prevalent cancer type was breast cancer (47%). Long-acting G-CSF was used in 38 patients (67%). Only 47% of patients were treated with steroids. Conclusion: Although the benefit of G-CSF treatment outweighs the potential damage, oncologists should consider the possibility of triggering a vascular toxicity and try to identify patients at increased risk for this side effect.

Lay abstract Background: Several case reports suggest that a type of drug called granulocyte colony-stimulating factor (G-CSFs) may, in rare cases, produce serious side effects, such as vasculitis. Materials & methods: A systematic search was conducted to describe this unusual side effect. Results: Fifty-seven patients were analyzed. The most prevalent cancer type in which this side effect was observed was breast cancer (47%). Only 47% of patients were treated with steroids. The main symptoms, such as fever, chest/epigastric pain and general malaise, are nonspecific and cannot be used to diagnose the side effect; laboratory findings are suggestive of inflammation. Conclusion: Accurate assessment of what causes this adverse event is extremely important. Although the benefit of G-CSF treatment outweighs the potential damage, oncologists should consider the possibility of triggering vascular toxicity and try to identify patients at increased risk.

Long-acting granulocyte colony-stimulating factor pegfilgrastim (lipegfilgrastim) for stem cell mobilization in multiple myeloma patients undergoing autologous stem cell transplantation.

Autologous stem cell transplantation (ASCT) is a standard of care in newly-diagnosed multiple myeloma (MM) patients. Several studies before the introduction of novel therapies in MM, demonstrated a pegylated G-CSF to be successful in mobilizing peripheral blood stem cells (PBSCs). Lipegfilgrastim is a novel long-acting G-CSF that is produced by the conjugation of a single 20-kDa polyethelene glycol to the natural O-glycosylation site of G-CSF. Twenty-four MM patients were included for PBSCs mobilization with a single SC injection of 6 mg lipegfilgrastim. PBSC collection was started when the CD34+ count was > 10 × 106 cells/L. The target progenitor cells were 6 × 106 cells/kg. The median day of apheresis was + 3 (range 2-5) following lipegfilgrastim. Median peripheral blood CD34+ count pre-mobilization was of 22.65 (range 3.36-105) × 106 cells/L. The median number of leukaphaeresis procedures was 2 (range 1-4). The median mobilized CD34+ cells/kg were 8.26 (range 0.77-12.42). One patient failed to mobilize and two patients mobilized < 6 × 106 cells/kg. Toxicity was mild and transient. Twenty-three patients underwent ASCT following high dose melphalan. All patients engrafted. As lipegfilgrastim is administered only once, it is conceivable that it improves both compliance and quality-of-life (NCT02488382).

Same-day versus next-day pegfilgrastim or pegfilgrastim-cbqv in patients with lymphoma receiving CHOP-like chemotherapy.

Aim: To compare the incidence of febrile neutropenia and related outcomes of prophylactic same-day versus next-day pegfilgrastim/pegfilgrastim-cbqv in patients with lymphoma receiving cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone (CHOP)-like chemotherapy. Methods: Retrospective, real-world, single-institution study. Results: 93 patients received 460 cycles of CHOP-like chemotherapy. The incidence of febrile neutropenia and grade 3/4 chemotherapy-induced neutropenia was 5 and 16.5%, respectively. In 401 cycles pegfilgrastim was administered same-day versus 12 cycles next-day. Febrile neutropenia occurred in 17 cycles versus 0 cycles (p = 1.00) and grade 3/4 chemotherapy-induced neutropenia in 65 cycles (16.2%) versus 1 cycle (16.7%; p = 1.00) with same-day versus next-day pegfilgrastim administration, respectively. Conclusion: Pegfilgrastim may be safely administered on the same day as chemotherapy in patients with lymphoma receiving CHOP-like chemotherapy.

Lay abstract Aside from killing cancer cells, chemotherapy can also affect the growth of immune cells that normally prevent infections. Without enough of these immune cells in the blood, the patient's body cannot fight infections. This can lead to a serious condition called febrile neutropenia, and death in the most severe cases. Pegfilgrastim, a growth factor that helps important types of immune cells to grow, can prevent this side effect of chemotherapy. Usually, pegfilgrastim is administered the day after chemotherapy but there is a trend to administer it on the day of chemotherapy, but whether this is effective and safe is currently unclear. This study from the University of Arizona Cancer Center showed that administration of pegfilgrastim on the same day as chemotherapy is a safe, effective method of preventing febrile neutropenia in patients who receive standard-of-care chemotherapy to treat lymphoma.

Clozapine rechallenge following neutropenia using granulocyte colony-stimulating factor: A Quebec case series.

BACKGROUND: Clozapine has a unique efficacy profile among individuals suffering from treatment-resistant schizophrenia, but is associated with hematological side effects. The use of granulocyte colony-stimulating factors (G-CSF) to allow clozapine continuation or rechallenge has emerged as a promising option, but evidence is still scarce. AIM: To describe the largest case series so far published regarding this practice. METHOD: A national clozapine hematological monitoring database was consulted to identify all patients who had had neutrophil count <1.5 × 109/L since 2004 in Quebec and was cross-referenced with hospital pharmacy software to identify patients who had received at least one dose of G-CSF, such as filgrastim, while being exposed to clozapine. All data were collected retrospectively, using patients' medical files, from January to July 2019. RESULTS: Using G-CSF, three out of eight patients could maintain clozapine despite neutropenia episodes that otherwise would have required treatment discontinuation. The only side effect reported was mild short-lived back pain, over a mean 3-year follow-up period. In all but one case, filgrastim was used on an "as-needed" basis at doses of 300 mcg administered subcutaneously. CONCLUSION: These results suggest that the "as-needed" use of G-CSF is well-tolerated and may allow clozapine rechallenge in some well-selected patients, adding to the paucity of data regarding long-term safety and efficacy of this strategy. More research may help to better define potential candidates and optimal regimen of such practice.

Optimizing the timing of 3.6 mg Pegfilgrastim Administration for Dose-Dense Chemotherapy in Japanese Patients with Breast Cancer.

Perioperative dose-dense chemotherapy (DDCT) with pegfilgrastim (Peg) prophylaxis is a standard treatment for high-risk breast cancer. We explored the optimal timing of administration of 3.6 mg Peg, the dose approved in Japan. In the phase II feasibility study of DDCT (adriamycin+cyclophosphamide or epirubicin+cyclophosphamide followed by paclitaxel) for breast cancer, we investigated the feasibility, safety, neutrophil transition, and optimal timing of Peg treatment by administering Peg at days 2, 3, and 4 post-chemotherapy (P2, P3, and P4 groups, respectively). Among the 52 women enrolled, 13 were aged > 60 years. The anthracycline sequence was administered to P2 (n=33), P3 (n=5), and P4 (n=14) patients, and the taxane sequence to P2 (n=38) and P3 (n=6) patients. Both sequences showed no interaction between Peg administration timing and treatment discontinuation, treatment delay, or dose reduction. However, the relative dose intensity (RDI) was significantly different among the groups. The neutrophil count transition differed significantly among the groups receiving the anthracycline sequence. However, the neutrophil count remained in the appropriate range for both sequences in the P2 group. The timing of Peg administration did not substantially affect the feasibility or safety of DDCT. Postoperative day 2 might be the optimal timing for DDCT.

Conversion to supportive care with biosimilar pegfilgrastim-cbqv enables budget-neutral expanded access to R-CHOP treatment in non-Hodgkin lymphoma.

This pharmacoeconomic simulation (1) assessed the cost-efficiency of converting a panel of 20,000 patients at risk of chemotherapy-induced (febrile) neutropenia (CIN/FN) from reference pegfilgrastim to biosimilar pegfilgrastim-cbqv; (2) estimated how savings can be used to provide budget-neutral expanded access to R-CHOP therapy for non-Hodgkin lymphoma patients; and 3) determined the number-needed-to-convert (NNC) to purchase one additional dose of R-CHOP (US payer perspective). Model inputs included biosimilar conversion from pre-filled syringe [PFS] or on-body injector [OBI] reference pegfilgrastim; age-proportional blended costs for reference pegfilgrastim PFS and OBI, pegfilgrastim-cbqv and R-CHOP; medication administration costs; biosimilar conversion rates of 10-100 %; and 1-6 cycles of prophylaxis. Cost-savings were used to estimate the number of doses of R-CHOP that could be purchased and the NNC to purchase one additional dose. Converting a panel of 20,000 patients requiring CIN/FN prophylaxis to biosimilar pegfilgrastim-cbqv from a low of 1 cycle and 10 % conversion to a high of 6 cycles and 100 % conversion yielded savings from $1,567,195 to $96,668,126. The budget-neutral acquisition of R-CHOP doses afforded by these savings ranged from 227 to 13,999 doses, the latter enabling 2333 patients to receive 6 cycles of R-CHOP treatment with no additional cost to the payer. These results are achieved if all 20,000 panel patients requiring GCSF support are prophylacted with biosimilar pegfilgrastim-cbqv for 6 cycles, yielding an NNC of 1.43 patients per additional R-CHOP dose. This simulation underscores the clinic-economic benefit of prophylaxis with biosimilar growth factor and pegfilgrastim-cbqv specifically.

Prophylactic pegfilgrastim to prevent febrile neutropenia among patients receiving biweekly (Q2W) chemotherapy regimens: a systematic review of efficacy, effectiveness and safety.

BACKGROUND: Pegfilgrastim, a long-acting granulocyte colony-stimulating factor (G-CSF), is commonly used to prevent febrile neutropenia (FN), a potentially life-threatening complication, following myelosuppressive chemotherapy. The FDA label for pegfilgrastim specifies that it should not be administered 14 days before or within 24 h of administration of myelosuppressive chemotherapy, precluding the use of pegfilgrastim in biweekly (Q2W) regimens. The National Comprehensive Cancer Network and the European Organisation for Research and Treatment of Cancer guidelines support the use of prophylactic pegfilgrastim in patients receiving Q2W regimens. The objective of this study was to systematically review evidence from randomized clinical trials (RCTs) and observational studies that describe the effectiveness and safety of prophylactic pegfilgrastim in preventing FN among patients receiving Q2W regimens. METHODS: An Ovid MEDLINE, Embase, and Cochrane Library literature search was conducted to evaluate the evidence regarding efficacy, effectiveness, and safety of prophylactic pegfilgrastim versus no prophylactic pegfilgrastim or prophylaxis with other G-CSF in patients who were receiving Q2W chemotherapy regimens with high (> 20%) or intermediate (10-20%) risk of FN for a non-myeloid malignancy. Studies that addressed absolute or relative risk of FN, grade 1-4 neutropenia, all-cause or any hospitalization, dose delays or dose reductions, adverse events, or mortality were included. Studies where the comparator was a Q3W chemotherapy regimen with primary prophylactic pegfilgrastim were also included. RESULTS: The initial literature search identified 2258 publications. Thirteen publications met the eligibility criteria, including eight retrospective, one prospective, one phase 1 dose escalation study, and three RCTs. In nine of the 13 studies reporting incidence of FN, and in seven of the nine studies reporting incidence of neutropenia, administration of prophylactic pegfilgrastim in patients receiving Q2W regimens resulted in decreased or comparable rates of FN or neutropenia compared with patients receiving filgrastim, no G-CSF, lipefilgrastim or pegfilgrastim in Q3W regimens. In six of the nine studies reporting safety data, lower or comparable safety profiles were observed between pegfilgrastim and comparators. CONCLUSIONS: In a variety of non-myeloid malignancies, administration of prophylactic pegfilgrastim was efficacious in reducing the risk of FN in patients receiving high- or intermediate-risk Q2W regimens, with an acceptable safety profile. TRIAL REGISTRATION: PROSPERO registration no: CRD42019155572 .

Filgrastim alone versus cyclophosphamide and filgrastim for mobilization in multiple myeloma patients.

BACKGROUND AND OBJECTIVE: High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) is standard treatment approach in most multiple myeloma (MM) patients. Before ASCT, chemomobilization or only granulocyte-colony stimulating factor (G-CSF) mobilization can be preferred in stem cell mobilization. The primary aim of the study is to compare the effect of the two mobilization regimens on hematopoietic engraftment times, CD34+cell counts and number of apheresis required to harvest stem cells. MATERIALS AND METHODS: The records of MM patients who applied to our hospital between 2010 and 2020 were analysed retrospectively. Patients were divided into two groups (Group A: Cyclophosphamide plus filgrastim, Group B: Filgrastim alone) according to the mobilization regimen. RESULTS: A total of 223 MM patients were included in this study (Group A:153, Group B:70 patients). When the patients in Group A and Group B were compared, the number of collected CD34+ cells were higher in Group A (p < 0.001). However, there was no significant difference between the two groups in terms of median times to neutrophil and platelet engraftment, and number of apheresis required to harvest stem cells (p > 0.05). The rate of infection development during mobilization in the patients in group A and the duration of hospitalization of these patients were higher than the patients in group B (p < 0.001). Patients receiving >6 cycles of chemotherapy and immunomodulatory treatment had lower collected CD34+ cells than other patients (p = 0.012 and p = 0.054). CONCLUSION: Based on our findings, filgrastim alone seems to provide a sufficient amount of stem cells in MM patients.

Economic and clinical outcomes of pegfilgrastim via prefilled syringe vs on-body injector: a real-world data analysis.

BACKGROUND: Pegfilgrastim is available as a prefilled syringe (PFS) and an on-body injector (OBI). Whether the administration method of pegfilgrastim affects the effectiveness and health care resources has not been evaluated in the setting of routine care. OBJECTIVE: To compare real-world clinical and economic outcomes between PFS and OBI methods of administration. METHODS: This was a retrospective observational study in patients diagnosed with breast cancer or non-Hodgkin lymphoma who received myelosuppressive chemotherapy and prophylactic use of pegfilgrastim via PFS or OBI between January 1, 2017, and May 31, 2018, according to MarketScan research databases. A propensity score was used to match the PFS cohort 1:1 to the OBI cohort. Outcomes were compared among the matched cohorts using a generalized linear model and generalized estimating equations with log-link function. RESULTS: 3,152 patients were identified. After matching, the final sample included 2,170 patients, representing 1,085 in each cohort. The incidence of febrile neutropenia (FN) in the first chemotherapy cycle was 1.01% for OBI (95% CI = 0.56-1.82) vs 1.48% for PFS (95% CI = 0.91-2.39; P = 0.336). In all chemotherapy cycles (total cycles = 7,467), the FN incidence was 0.91% for OBI (95% CI = 0.64-1.30) vs 1.22% for PFS (95% CI = 0.90-1.64; P = 0.214). There was no statistically significant difference in adjusted per-member per-month all-cause total cost health care resource utilization (HCRU) for hospitalizations, emergency department visits, and pharmacy claims. CONCLUSIONS: In a matched cohort of patients representing real-world utilization, there was no statistically or clinically meaningful difference in FN incidence between OBI and PFS methods of pegfilgrastim administration. There was no difference in total HCRU or total costs. OBI and PFS methods of administration are both indicated for patients requiring prophylactic pegfilgrastim, which is important considering that biosimilar PFS options are now available. DISCLOSURES: This study was funded by Sandoz, Inc. Wang, Li, and K. Campbell are employees of Sandoz, Inc. Schroader and D. Campbell are employees of Xcenda, which was contracted by Sandoz, Inc., to provide study and manuscript development. McBride reports receiving payment from Sandoz, Inc., as a consultant, unrelated to this study; Coherus for advisory board and speaker engagements; and Pfizer for advisory board participation during the time of this study.

Uptake and cost of biosimilar filgrastim among Medicare and Medicaid populations in 2015-2018.

BACKGROUND: The first biosimilar product filgrastim-sndz was approved by the FDA in 2015, but real-world evaluations of its uptake and cost in nationally representative populations are limited. OBJECTIVE: To evaluate the uptake and cost of filgrastim-sndz, relative to its originator filgrastim and alternative biologic tbofilgrastim, among Medicare and Medicaid populations. METHODS: Using the annually aggregated, product-level utilization and cost data of biologic and biosimilar filgrastim products in 2015-2018 from CMS drug spending data, total number of claims and costs for all 3 filgrastim products were identified and extracted for Medicare Part B, Part D, and Medicaid reimbursement. Annual average cost per claim and per beneficiary of individual filgrastim products were also extracted, and their annual growth rates were calculated. RESULTS: Three years after entering the US market, use of filgrastim-sndz increased to 49.1% and 46.0% of all filgrastim claims paid by Medicare Parts B and D, respectively, and to 38.7% of filgrastim Medicaid claims in 2018. Total cost for filgrastim-sndz also reached 42.8%, 41.8%, and 26.9% of all filgrastim products paid by Medicare Parts B and D and Medicaid, respectively. Significant reductions in average cost per claim for filgrastim-sndz in 2017 and 2018 were observed in Medicare Part B and Medicaid. CONCLUSIONS: Significant uptake of biosimilar filgrastim in Medicare and Medicaid programs occurred during the first 3 years of marketing. Policymakers may use the evidence to evaluate existing barriers and policies regarding biosimilar adoption. DISCLOSURES: No outside funding supported this work. The author has no conflicts of interest to disclose.

Comparing the efficacy and side-effects of PDLASTA® (Pegfilgrastim) with PDGRASTIM® (Filgrastim) in breast cancer patients: a non-inferiority randomized clinical trial.

BACKGROUND: The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. METHODS: In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. RESULTS: Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC (p = 0.527), Hgb (p = 0.075), Platelet (p = 0.819), Neutrophil (p = 0.575), Lymphocyte (p = 705) and ANC (p = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. CONCLUSION: It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia. TRIAL REGISTRATION: IRCT20190504043465N1 , May 2019.

Lenograstim versus filgrastim in mobilization before autologous hematopoietic stem cell transplantation in patients with multiple myeloma and lymphoma - Single center experience.

OBJECTIVE: Peripheral blood stem cell transplantation is frequently used in the treatment of various hematological malignancies after intensive chemotherapy. The primary aim of our study is to compare the amount of collected CD34+ cells and engraftment times in patients mobilized with filgrastim or lenograstim. MATERIAL AND METHODS: Demographic and clinical data of multiple myeloma (MM) and lymphoma patients who underwent autologous transplantation and mobilized with G-CSF (filgrastim or lenograstim) without chemotherapy were collected retrospectively. RESULTS: One hundred eleven MM and 58 lymphoma patients were included in the study. When mobilization with filgrastim and lenograstim was compared in MM patients, there was no significant difference in neutrophil and thrombocyte engraftment times of lenograstim and filgrastim groups (p = 0.931 p = 0.135, respectively). Similarly, the median number of CD34+ cells collected in patients receiving filgrastim and lenograstim was very similar (4.2 × 106/kg vs 4.3 × 106/kg, p = 0.977). When compared with patients who received lenalidomide before transplantation and patients who did not receive lenalidomide, the CD34+ counts of the two groups were similar. However, neutrophil and platelet engraftment times in the group not receiving lenalidomide tended to be shorter (p = 0.095 and p = 0.12, respectively). When lymphoma patients mobilized with filgrastim and lenograstim were compared, neutrophil engraftment time (p = 0.498), thrombocyte engraftment time (p = 0.184), collected CD34+ cell counts (p = 0.179) and mobilization success (p = 0.161) of the groups mobilized with filgrastim and lenograstim were similar. CONCLUSION: The superiority of the two agents to each other could not be demonstrated. Multi-center prospective studies with larger numbers of patients are needed.