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International Journal of Radiation... Nov 2023Patients exposed to acute high doses of ionizing radiation are susceptible to dose-dependent bone marrow depression with resultant pancytopenia. Romiplostim (RP; Nplate)...
PURPOSE
Patients exposed to acute high doses of ionizing radiation are susceptible to dose-dependent bone marrow depression with resultant pancytopenia. Romiplostim (RP; Nplate) is a recombinant thrombopoietin receptor agonist protein that promotes progenitor megakaryocyte proliferation and platelet production and is an approved treatment for patients with chronic immune thrombocytopenia. The goal of our study was to evaluate the postirradiation survival and hematologic benefits of a single dose of RP with or without pegfilgrastim (PF; Neulasta, granulocyte colony stimulating factor) by conducting a well-controlled, treatment-concealed, good laboratory practice-compliant study in rhesus macaques that was compliant with the United States Food and Drug Administration Animal Rule regulatory approval pathway.
METHODS AND MATERIALS
Irradiated male and female rhesus macaques (20/sex in each of 3 groups: control, RP, and RP + PF) were subcutaneously administered vehicle or RP (5 mg/kg, 10 mL/kg) on day 1 in the presence or absence of 2 doses of PF (0.3 mg/kg, 0.03 mL/kg, days 1 and 8). Total body radiation (680 cGy, 50 cGy/min from cobalt-60 gamma ray source) occurred 24 ± 2 hours previously at a dose targeting 70% lethality for the control cohort over 60 days. The study examined 60-day survival postirradiation as the primary endpoint. Secondary endpoints included incidence, severity, and duration of thrombocytopenia and neutropenia, other hematology parameters, coagulation parameters, and body weight change to provide insights into potential mechanisms of action.
RESULTS
Compared with sham-treated controls, treated animals demonstrated a 40% to 55% survival benefit compared with controls, less severe clinical signs, reduced incidence of thrombocytopenia and/or neutropenia, earlier hematologic recovery, and reduced morbidity from bacterial infection.
CONCLUSIONS
These results were pivotal in obtaining Food and Drug Administration approval in January 2021 for RP's new indication as a single administration therapy to increase survival in adults and pediatric patients acutely exposed to myelosuppressive doses of radiation.
Topics: Adult; Animals; Humans; Male; Female; Child; Macaca mulatta; Recombinant Proteins; Thrombocytopenia; Neutropenia; Hematology; Radiation Exposure
PubMed: 37224926
DOI: 10.1016/j.ijrobp.2023.05.008 -
BMC Health Services Research May 2023Febrile neutropenia associated with some chemotherapy regimens can lead to potentially fatal complications and high health care costs. Administration of pegfilgrastim... (Observational Study)
Observational Study
BACKGROUND
Febrile neutropenia associated with some chemotherapy regimens can lead to potentially fatal complications and high health care costs. Administration of pegfilgrastim using an On-Body Injector (OBI) may be more convenient for cancer patients and physicians in countries with limited access to high-complexity healthcare. This study aims to describe physician and nurse preferences regarding different options for administration of pegfilgrastim at cancer centers, the chemotherapy schemes for which pegfilgrastim is most frequently prescribed and how healthcare providers prioritize certain administration schemes according to patients' access to healthcare services.
METHODS
Observational, descriptive, cross-sectional study and survey, conducted between 2019 and 2020, to describe physician and nurse preferences regarding options for administration of pegfilgrastim at cancer centers, the demographics of the study population and characteristics of participating cancer centers. It included 60 healthcare professionals practicing at oncology centers from 8 cities in Colombia who were contacted and surveyed via telephone. Quantitative continuous variables were summarized using central tendency and dispersion measures.
RESULTS
It was found that 35% of participants are haemato-oncologists, oncologists or hematologists, 30% are general practitioners, and 35% are other healthcare professionals (i.e., nurse, oncology nurse and head nurse). Our study shows that 48% of physicians prefer the use of OBI, particularly in the scheme of 24 h after myelosuppressive chemotherapy administrations. Regardless of patient frailty and travel time to the clinic, over 90% of healthcare providers (HCPs) prefer to prioritize preventing the patient from having to return to the clinic for pegfilgrastim administration as well as to increase healthcare staff availability through the use of OBI.
CONCLUSIONS
The present study is the first one in Colombia that sought the reasons behind HCPs' choice to use OBI pegfilgrastim. Our results indicate that most professionals prefer to avoid the patient having to re-enter the care center for pegfilgrastim administration to facilitate access to healthcare for patients; patient characteristics and ease of transport are determining factors for respondents when choosing an option for drug administration. We found OBI is the preferred alternative by most HCPs and a good resource optimization strategy in the context of cancer patients' health care in Colombia.
Topics: Humans; Colombia; Cities; Cross-Sectional Studies; Ambulatory Care Facilities; General Practitioners
PubMed: 37221537
DOI: 10.1186/s12913-023-09454-z -
Annals of Hematology Jul 2023Multiple myeloma (MM) is the main indication for autologous stem cell transplantation (ASCT). Novel supportive therapies (e.g., granulocyte colony-stimulating factor)...
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 × 10/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.
Topics: Humans; Male; Middle Aged; Female; Filgrastim; Melphalan; Multiple Myeloma; Hematopoietic Stem Cell Transplantation; Biosimilar Pharmaceuticals; Prospective Studies; Retrospective Studies; Transplantation, Autologous; Granulocyte Colony-Stimulating Factor; Polyethylene Glycols; Recombinant Proteins
PubMed: 37079070
DOI: 10.1007/s00277-023-05228-z -
Journal of Pharmaceutical Health Care... Apr 2023
PubMed: 37060091
DOI: 10.1186/s40780-023-00284-z -
Frontiers in Oncology 2023A chemotherapy of rituximab, fludarabine and cyclophosphamide (R-FC) has been accepted as a promising frontline chemotherapy in selected patients with chronic...
Effectiveness of pegfilgrastim prophylaxis in preventing febrile neutropenia during R-FC chemoimmunotherapy for chronic lymphocytic leukemia: A multicenter prospective phase II study.
BACKGROUND
A chemotherapy of rituximab, fludarabine and cyclophosphamide (R-FC) has been accepted as a promising frontline chemotherapy in selected patients with chronic lymphocytic leukemia (CLL). Although R-FC regimen is a relatively dose-dense regimen and neutropenia incidence is more than 50%, primary prophylactic pegfilgrastim was not fully recommended in the clinical field. Therefore, the study evaluated the prophylactic effectiveness of pegfilgrastim to reduce the incidence of febrile neutropenia associated with R-FC of patients with CLL.
PATIENTS AND METHODS
A single-arm, multicenter, prospective phase II study was designed to assess the efficacy of prophylactic pegfilgrastim. Thirty-four CLL patients were enrolled and analyzed for neutropenia and other related factors, and comparative analysis was performed with historical cohort.
RESULTS
Compared with our historical cohort, incidence of grade 3-4 neutropenia and febrile neutropenia was remarkably reduced during any cycle of chemotherapy (14.7% vs. 48.2% of study cohort vs. historical cohort during C1, 5.9% vs. 65.8% during C2, 12.9% vs. 80.6% during C3, 10% vs. 84.6% during C4, 3.4% vs. 83.6% during C5, and 10.7% vs. 85.7% during C6, p <0.001). Also, cumulative incidence of disrupted chemotherapy was noticeably reduced in study cohort on any cycles of R-FC regimen (8.8% vs. 22.2% of study cohort vs. historical cohort on C2, 9.7% vs. 25.2% on C3, 13.4% vs. 26.9% on C4, 13.8% vs. 45.2% on C5, 17.9% vs. 47.3% on C6, p=0.007). In addition, treatment-related mortality was 5.9%, which significantly reduced compared to 9.6% of our historical cohort (HR 0.64, 95% CI 0.42-0.79, P = 0.032).
CONCLUSION
Primary prophylactic pegfilgrastim is effective in the prevention of neutropenia/febrile neutropenia, and infection-related mortality during R-FC regimen in patients with CLL.
PubMed: 37056335
DOI: 10.3389/fonc.2023.998014 -
Current Oncology (Toronto, Ont.) Mar 2023Lapelga was approved by Health Canada as a pegfilgrastim biosimilar in 2019 and remains the most commonly used biosimilar in Ontario and is fully reimbursed under the... (Review)
Review
BACKGROUND
Lapelga was approved by Health Canada as a pegfilgrastim biosimilar in 2019 and remains the most commonly used biosimilar in Ontario and is fully reimbursed under the Ontario Drug Benefit program in this category. We explored the efficacy and tolerability of Lapelga in a retrospective analysis of patients with early breast cancer who underwent adjuvant chemotherapy supported with Lapelga as a primary prophylaxis.
METHODS
Adult patients with early breast cancer treated with adjuvant chemotherapy at the London Regional Cancer Program in London, ON, Canada between May 2019 and June 2022 were included. All of these patients were supported with Lapelga as the primary prophylaxis. Patients' age, tumour, and nodal status, their type of chemotherapy, co-morbid conditions, and incidence of febrile neutropenia (FN) and its related details as well as any reported side effects to Lapelga were collected.
RESULTS
A total of 201 patients were included in this review with majority (78%) of patients under 65 years of age. One third of patients were treated with the adriamycin and cyclophosphamide (AC)-Paclitaxel dose dense chemotherapy and a quarter of patients with either a docetaxel and cyclophosphamide (TC) combination or an AC-dose dense with Paclitaxel weekly, and 10% or less patients had FEC-D (5-fluorouracil, epirubicin, and cyclophosphamide) and AC chemotherapy. FN incidence was only 3.48% in this review (7/201 patients). Patients with FN were admitted to hospital and recovered completely with no mortality reported. No cases of a switch to a different granulocyte colony growth factor were seen. The most frequent side effects from Lapelga included musculoskeletal pain, fever, and headache. However, the majority of patients (88.6%; 178/201) did not have any reported side effects specifically assigned to Lapelga.
CONCLUSIONS
In this single centre retrospective study, early breast cancer patients (n = 201) treated with adjuvant chemotherapy supported with primary prophylaxis with Lapelga had a low incidence of FN (3.48%). This supports Lapelga being an effective strategy as the primary prophylaxis when used with common chemotherapy regimens in the real-world setting.
Topics: Adult; Humans; Female; Breast Neoplasms; Retrospective Studies; Biosimilar Pharmaceuticals; Granulocyte Colony-Stimulating Factor; Cyclophosphamide; Doxorubicin; Paclitaxel; Ontario
PubMed: 36975457
DOI: 10.3390/curroncol30030244 -
The American Journal of Managed Care Mar 2023With the rapid decline in average sales price of reference pegfilgrastim products due to biosimilar competition, health care institutions and payers may grapple with...
With the rapid decline in average sales price of reference pegfilgrastim products due to biosimilar competition, health care institutions and payers may grapple with coverage of Neulasta Onpro.
Topics: Humans; Filgrastim; Polyethylene Glycols; Biosimilar Pharmaceuticals
PubMed: 36947018
DOI: 10.37765/ajmc.2023.89331 -
Cureus Jan 2023Introduction Biologic drugs are used to treat various illnesses like autoimmune diseases, cancers, hormonal irregularities, anemia, etc., and to prevent various diseases...
Introduction Biologic drugs are used to treat various illnesses like autoimmune diseases, cancers, hormonal irregularities, anemia, etc., and to prevent various diseases as vaccines. Though various biologic drugs are already available, they are still not within reach of the common man due to financial constraints. Through many search engines, studies evaluating the cost variation of different brands of biologics were investigated; however, only a few studies that address this problem were found. Hence, this study was planned with the objective of addressing the cost variation of various brands of biologic medicines available in the Indian market. Methods The website for the Current Index of Medical Specialties (CIMS) for India's location was used to obtain the prices of the different brands of biologic medicines in Indian National Rupee (INR) currency, which different manufacturers market with identical forms in strength and dosage. The percentage cost variation and cost ratio were calculated with the help of the minimum and maximum prices of various brands of biologic drugs. Results The prices of biologics belonging to six different classes that are available in 23 formulations were analyzed. The highest cost variability was shown by pegfilgrastim 6 mg at 1,022.92%, and the minimum-cost variation was shown by darbepoetin alfa 200 mcg at 13.07%. Conclusion Our research found a vast variance in the costs of various brands of biologic medicines in India. The government should address this cost variation problem by developing various policies, such as breaking the monopoly of manufacturers, providing tax incentives to nonprofit generic medicine manufacturers, and incorporating more biologic drugs under the protection of the Drugs Prices Control Order (DPCO).
PubMed: 36820122
DOI: 10.7759/cureus.33943 -
Journal of Medical Economics 2023This study estimated, for Saudi Arabia, the cost-efficiency of converting patients from reference Neupogen and Neulastim to one of two filgrastim biosimilars (Nivestim,...
Cost-efficiency analysis of conversion to biosimilar filgrastim for supportive cancer care and resultant expanded access analysis to supportive care and early-stage HER2+ breast cancer treatment in Saudi Arabia: simulation study.
AIMS
This study estimated, for Saudi Arabia, the cost-efficiency of converting patients from reference Neupogen and Neulastim to one of two filgrastim biosimilars (Nivestim, Zarzio); the budget-neutral expanded access to supportive care with biosimilar filgrastim and therapeutic care to ado-trastuzumab emtansine thus afforded; and the number-needed-to-convert (NNC) to provide supportive or therapeutic treatment to one patient.
MATERIALS AND METHODS
Replicating prior studies, we modeled the cost-efficiencies gained from converting varying proportions of a hypothetical panel of 4,000 patients undergoing six cycles of cancer treatment from Neupogen or Neulastim to one of the two biosimilar G-CSF formulations, using national cost inputs. Cost-savings in USD were used to estimate the additional doses of biosimilar G-CSF and expanded access to ado-trastuzumab emtansine on a budget-neutral basis, and NNC to purchase one additional dose of supportive or therapeutic treatment.
RESULTS
Savings from conversion from reference to a biosimilar filgrastim were $3,086,400 (Nivestim) and $3,460,800 (Zarzio). With reference pegfilgrastim, savings from conversion were $11,712,240 (Nivestim) and $12,086,640 (Zarzio). Biosimilar conversion from reference to biosimilar filgrastim enabled expanded access to ado-trastuzumab emtansine ranging from 61 patients (5 days, Nivestim) to 191 patients (14 days, Zarzio). For supportive care, biosimilar conversion enabled expanded access ranging from 8,244 patients (5 days, Nivestim) to 25,882 patients (14 days, Zarzio). For biosimilar conversion from daily filgrastim, the NNC for treatment with ado-trastuzumab emtansine decreased as days of injections increased [5 days: 395 (Nivestim), 352 (Zarzio); 14 days: 141(Nivestim), 126 (Zarzio)]. Alternately, for biosimilar conversion from single-injection pegfilgrastim to daily biosimilar filgrastim, the NNC for treatment with ado-trastuzumab emtansine rose as days of injections increased, being highest under the 14-day scenario (146, Nivestim; 130, Zarzio).
CONCLUSION
This simulation study demonstrated significant potential cost-savings from biosimilar conversion. These savings provide budget-neutral increased access to supportive and therapeutic cancer care.
Topics: Humans; Female; Filgrastim; Biosimilar Pharmaceuticals; Breast Neoplasms; Ado-Trastuzumab Emtansine; Saudi Arabia; Granulocyte Colony-Stimulating Factor
PubMed: 36815700
DOI: 10.1080/13696998.2023.2183680 -
BMC Cancer Feb 2023Breast 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... (Observational Study)
Observational Study
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 × 10/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 × 10/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.
Topics: Humans; Female; Breast Neoplasms; Prospective Studies; Granulocyte Colony-Stimulating Factor; Filgrastim; Febrile Neutropenia; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Doxorubicin
PubMed: 36803350
DOI: 10.1186/s12885-023-10603-0