Search Results (7)

(1) Background: High-dose chemotherapy (HDCT) followed by autologous stem cell transplantation (ASCT) is the standard consolidation strategy for patients with newly diagnosed multiple myeloma (MM) and for a subset of patients with relapsed/refractory disease. For stem cell mobilization, G-CSF alone or in combination with chemotherapy mobilizing agents and/or plerixafor are commonly used. Ixazomib is an oral proteasome inhibitor with less neurotoxic potential, which previously showed the ability to mobilize stem cells in preclinical studies. (2) Methods: Prospective single-center phase 1 study assessing the efficacy and safety of stem cell mobilization with ixazomib and G-CSF in patients with newly diagnosed or relapsed/refractory MM undergoing HDCT and ASCT. Primary endpoint was percentage of patients achieving a yield of at least 6.0 × 10⁶/kg CD34+ cells within the first apheresis. G-CSF (filgrastim) 10 μg/kg/day was administered subcutaneously (s.c.) from day 1 to day 5 (planned apheresis) and ixazomib 4 mg orally at day 4. Plerixafor 24 mg s.c. was administered if the stem cell mobilization with ixazomib and G-CSF was not sufficient. (3) Results: 19 patients were treated within the study between 06/2020 and 02/2021. The primary endpoint was reached in 17 (89%) patients, with a median of 7.1 × 10⁶/kg CD34+ cells collected within the first apheresis, comparable to previously published results, and only 2 (11%) patients required a second apheresis. Median number of circulating CD34+ cells was 14.0 × 10⁶/L (2.0–95.2) before the administration of ixazomib, and 33.0 × 10⁶/L (4.2–177.0) pre-apheresis. However, 9 (47%) patients required the addition of plerixafor to ensure optimal stem cell collection. (4) Conclusions: The combination of ixazomib and G-CSF showed promising stem cell mobilizing activity in patients with MM prior to HDCT and ASCT. Future larger studies might further investigate the role of ixazomib in stem cell mobilization regimens for MM. Full article

Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients (n = 47, 56.1 ± 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ≤ 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: −12.7 g, treatment: −19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial. Full article

The hematopoietic granulocyte-colony stimulating growth factor (G-CSF, filgrastim) is an approved drug in hematology and oncology. Filgrastim’s potential in neurodegenerative disorders is gaining increasingly more attention, as preclinical and early clinical studies suggest it could be a promising treatment option. G-CSF has had a tremendous record as a safe drug for more than three decades; however, its effects upon the central nervous system (CNS) are still not fully understood. In contrast to conceptual long-term clinical application with lower dosing, our present pilot study intends to give a first insight into the molecular effects of a single subcutaneous (s.c.) high-dose G-CSF application upon different regions of the rodent brain. We analyzed mRNA—and in some instances—protein data of neurogenic and non-neurogenic differentiation markers in different regions of rat brains five days after G-CSF (1.3 mg/kg) or physiological saline. We found a continuous downregulation of several markers in most brain regions. Remarkably, cerebellum and hypothalamus showed an upregulation of different markers. In conclusion, our study reveals minor suppressive or stimulatory effects of a single exceptional high G-CSF dose upon neurogenic and non-neurogenic differentiation markers in relevant brain regions, excluding unregulated responses or unexpected patterns of marker expression. Full article

Neutropenia and febrile neutropenia are common and potentially life-threating events associated with chemotherapy treatment in Hodgkin lymphoma (HL). Neutropenia-related infectious events could be an issue both for direct clinical consequences and for delay in treatment delivery, affecting final outcomes in a potentially highly curable disease. Pegfilgrastim is the pegylated form of filgrastim, the recombinant form of human G-CSF, capable of prevent and mitigate neutropenic effects of chemotherapy, when adopted as primary prophylaxis in several hematological malignancies. No updated version of major international guidelines provides clear indication on prophylaxis use of pegfilgrastim in HL to prevent febrile neutropenia episodes in HL. Moreover, to date, scarce and non-uniform clinical experiences evaluating pegfilgrastim as prophylaxis in HL are present in the literature. Herein, we propose a brief summary of the literature data about efficacy and safety of the use of pegfilgrastim as primary prophylaxis in HL during chemotherapy treatment. Full article

The primary prophylaxis with filgrastim (FIL) and pegfilgrastim (PEG-F) is recommended to decrease the severity of chemotherapy-induced neutropenia (CIN). The commonly reported adverse drug reactions (ADRs) with FIL and PEG-F is bone pain. ADRs pertaining to FIL and PEG-F were extracted from the European EudraVigilance (EV) database. The Individual Case Safety Reports (ICSRs) obtained from EV database that reported FIL and PEG-F as the suspected drug were analyzed. Registered ADRs (from the groups “General disorders and administration site conditions”, “Blood and lymphatic system disorders”, “Musculoskeletal and connective tissue disorders” and “Investigations”) for FIL and PEG-F were collected from EV database from 2007 to 5 June 2021. The reporting odds ratio (ROR) was used to calculate ICSRs with most common ADRs related to FIL and PEG-F. A total of 17,403 ICSRs described the incidence of most common ADRs of FIL and PEG-F. The commonly reported ADRs for both drugs were pyrexia, bone pain, back pain, neutropenia and febrile neutropenia. The odds ratio of ICSRs belonging to the System Organ Class (SOC) “Investigations” (ROR 1.01 (CI 0.93–1.10)) revealed no significant difference in FIL and PEG-F. However, for the SOCs (General disorders and administration site conditions” and “Musculoskeletal and connective tissue disorders” ((ROR 1.14 (CI 1.06–1.21); ROR 1.21 (CI 1.18–1.32), respectively), an increased reporting probability with PEG-F was found. The authors reported a lower reporting probability for the SOC “Blood and lymphatic system disorders” for FIL versus PEG-F (ROR 0.75 (CI 0.70–0.80)). Our results have demonstrated that the occurrence of bone pain was similar with FIL and PEG-F. For the incidence of pyrexia and back pain, PEG-F was associated with a higher reporting probability as compared to FIL. However, the incidence of neutropenia and febrile neutropenia was higher in FIL compared to PEG-F. Further evaluation of data from real life is needed. Full article

Background: The aim of this review and meta-analysis was to identify, assess, meta-analyze and summarize the comparative effectiveness and safety of filgrastim in head-to-head trials with placebo/no treatment, pegfilgrastim (and biosimilar filgrastim to update advances in the field. Methods: The preferred reporting items for systematic reviews and meta-analyses PRISMA statement were applied, and a random-effect model was used. Primary endpoints were the rate and duration of grade 3 or 4 neutropenia, and an incidence rate of febrile neutropenia. Secondary endpoints were time to absolute neutrophil count ANC recovery, depth of ANC nadir (lowest ANC), neutropenia-related hospitalization and other neutropenia-related complications. For filgrastim versus biosimilar filgrastim comparison, the primary efficacy endpoint was the mean difference in duration of severe neutropenia DSN. Results: A total of 56 studies were considered that included data from 13,058 cancer patients. The risk of febrile neutropenia in filgrastim versus placebo/no treatment was not statistically different. The risk ratio for febrile neutropenia was 0.58, a 42% reduction in favor of filgrastim. The most reported adverse event with FIL was bone pain. For pegfilgrastim versus filgrastim, no statistically significant difference was noted. The risk ratio was 0.90 (95% CI 0.67 to 1.12). The overall difference in duration of severe neutropenia between filgrastim and biosimilar filgrastim was not statistically significant. The risk ratio was 1.03 (95% CI 0.93 to 1.13). Conclusions: Filgrastim was effective and safe in reducing febrile neutropenia and related complications, compared to placebo/no treatment. No notable differences were found between pegfilgrastim and filgrastim in terms of efficacy and safety. However, a similar efficacy profile was observed with FIL and its biosimilars. Full article

Background: We retrospectively analysed relapsed/refractory MM (RRMM) patients treated with pomalidomide and dexamethasone (PomaD) either in real life, or previously enrolled in an interventional (STRATUS, MM-010) or currently enrolled in an observational study (MM-015) to provide further insights on safety and tolerability and clinical efficacy. Methods: Between July 2013 and July 2018, 76 RRMM patients (including 33 double refractory MM) received pomalidomide 4 mg daily given orally on days 1–21 of each 28-day cycle, and dexamethasone 40 mg weekly (≤75 years) or 20 mg weekly for patients aged > 75 years. In nine patients a third agent was added to increase the response: Cyclophosphamide (in two fit patients) or clarithromycin (in seven frail patients). Patients received subcutaneous filgrastim as part of the prophylaxis regimen for neutropenia. Results: A median number of six (range 2–21) PomaD cycles were given. The regimen was well tolerated with grade 3–4 haematological and non-haematological adverse events in 39 (51%) and 25 (33%) patients, respectively. In patients who developed serious AE, pomalidomide dose reduction (11%, 14%) or definitive discontinuation (18%, 23%) were applied. All patients have been evaluated for response within the first two cycles. The disease control rate (DCR), i.e., those patients that had a response equal or better than stable disease (≥ SD), was high (89%), with 44% overall response rate (ORR) after six cycles. The achieved best responses were complete remission (CR, 5%), very good partial remission (VGPR, 4%), partial remission (PR, 35%), minimal response (MR, 7%), and stable disease (SD, 38%). After a median follow up of 19.6 months, median progression free survival was 9.4 months, and overall survival (OS) was 19.02 months. Univariate analysis showed that double refractory patients, or who received more than three previous lines had shorter PFS. At 18 months, regardless of the depth of response, patients with a disease control of at least six months, defined as maintenance of a best clinical and/or biochemical response to treatment for almost six months, had prolonged PFS (35.3% versus 20.6%, p = 0.0003) and OS (81.2% versus 15.9%, p < 0.0001) Conclusions: Our findings indicate that PomaD is a safe and well-tolerated regimen in real-life, associated with prolonged PFS and OS with acceptable toxicity. Moreover, Pd induced disease control in most intensively pre-treated patients and some of them achieved longer PFS than that obtained with the previous treatment. Full article