Plerixafor 24mg/1.2ml solution for injection vials

BackgroundCytarabine (Ara-C) remains the cornerstone of remission-induction and consolidation chemotherapy for acute myeloid leukemia (AML) and related hematological malignancies. Despite more than six decades of clinical use, its multi-organ toxicity continues to be managed almost exclusively through dose attenuation and supportive care, with no approved upstream pharmacological prevention strategy available.ObjectivesThis scoping review aimed to systematically map the breadth and nature of pharmacological agents tested in vivo for their capacity to mitigate cytarabine-induced multi-organ toxicity, to characterize their mechanisms of action and organ targets, and to identify evidence gaps and agents with translational potential.MethodsThe review was designed and reported in accordance with the PRISMA-ScR checklist. A structured electronic search was conducted across PubMed/MEDLINE, Scopus, Cochrane Library and Embase, and Web of Science from database inception to 15 July 2025. Eligible studies were restricted to full-text, peer-reviewed, English-language research involving in vivo mammalian models administered cytarabine as the principal toxin, with at least one pharmacological co-intervention and at least one quantitative or histopathological organ-injury outcome.ResultsFrom 5701 retrieved records, 36 eligible in vivo mammalian studies (spanning 1964-2024) were identified. Included studies addressed neurotoxicity (n = 6), gastrointestinal mucositis (n = 9), ocular toxicity (n = 3), hepatotoxicity (n = 3), bone marrow suppression (n = 4), chemotherapy-induced alopecia (n = 5), and reproductive and developmental toxicity (n = 4). Five recurring mechanistic strategies were identified across the heterogeneous agents tested: redox buffering (N-acetylcysteine, α-lipoic acid, rutin, swertiamarin, α-tocopherol), mitochondrial preservation (betanin, thymoquinone, vitamin D, sodium zinc dihydrolipoylhistidinate [DHLHZn]), tissue-microenvironment reprogramming (apraglutide, BADGE, plerixafor, short-chain fatty acids, β-glucan), molecular antagonism (deoxycytidine, dCMP), and immunomodulation (lienal peptide, IL-1β, AHCC).ConclusionsThis scoping review provides the first systematic cartography of pharmacological mitigation strategies for cytarabine-induced multi-organ toxicity. Five mechanistic pathways converge across eight organ systems, with apraglutide and N-acetylcysteine representing the most clinically translatable candidates. Plerixafor and PPARγ blockade by BADGE constitute high-priority candidates for bone marrow niche protection, while the deoxycytidine antagonism principle warrants formal pharmacokinetic evaluation. The complete absence of cardiotoxicity mitigation data defines the most critical gap for future research.

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Gastric carcinoma (GC) remains a major global health challenge, requiring novel therapeutic approaches. This study investigates the efficacy of self-assembled M2pep-Cs NPs/Plerixafor nanoparticles in suppressing GC by targeting the CXCL12-CXCR4 signaling pathway and reprogramming tumor-associated macrophages (TAMs) to enhance anti-tumor immunity. The nanoparticles' physicochemical properties and biocompatibility are assessed using transmission electron microscopy, dynamic light scattering, and biological assays. A GC mouse model is established, followed by histological and immunohistochemical analyses to evaluate tumor apoptosis and proliferation. Multi-omics approaches, including transcriptomics, proteomics, and metabolomics, identify key genes and pathways affected by treatment. Flow cytometry and ELISA quantify immune activation markers; while, cell migration and invasion assays evaluate tumor suppression effects. The results demonstrate that M2pep-Cs NPs/Plerixafor effectively modulates the tumor microenvironment, suppressing GC progression by reprogramming TAMs through CXCL12-CXCR4 inhibition, enhancing immune recognition and T cell responses. This study provides mechanistic insights and highlights the potential of nanoparticle-based immunotherapy for GC, offering a promising avenue for clinical translation.

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MGTA-145 or GROβT, a CXCR2 agonist, has shown promising activity for hematopoietic stem cell (HSC) mobilization with plerixafor in pre-clinical studies and healthy volunteers. Twenty-five patients with multiple myeloma enrolled in a phase 2 trial evaluating MGTA-145 and plerixafor for HSC mobilization (NCT04552743). Plerixafor was given subcutaneously followed 2 h later by MGTA-145 (0.03 mg/kg) intravenously with same day apheresis. Mobilization/apheresis could be repeated for a second day in patients who collected 6 CD34+ cells/kg. Lenalidomide and anti-CD38 antibody were part of induction therapy in 92% (n = 23) and 24% (n = 6) of patients, respectively. Median total HSC cell yield (CD34+ cells/kg × 106) was 5.0 (range: 1.1-16.2) and day 1 yield was 3.4 (range: 0.3-16.2). 88% (n = 22) of patients met the primary endpoint of collecting 2 ×106 CD34+ cells/kg in ≤ two days, 68% (n = 17) in one day. Secondary endpoints of collecting 4 and 6 × 106 CD34+ cells/kg in ≤ two days were met in 68% (n = 17) and 40% (n = 10) patients. Grade 1 or 2 adverse events (AE) were seen in 60% of patients, the most common AE being grade 1 pain, usually self-limited. All 19 patients who underwent transplant with MGTA-145 and plerixafor mobilized HSCs engrafted successfully, with durable engraftment at day 100. 74% (17 of 23) of grafts with this regimen were minimal residual disease negative by next generation flow cytometry. Graft composition for HSCs and immune cells were similar to a contemporaneous cohort mobilized with G-CSF and plerixafor.

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BackgroundStem-cell mobilization in multiple myeloma is usually done with G-CSF with or without Cyclophosphamide (Cy) based chemotherapy/Plerixafor. Pre-clinical data suggest the role of proteasome inhibitors in mobilization. We previously reported that Bortezomib (Bort) when added to a Cy-based regimen had a better stem-cell yield. Consequent to favorable results with Bort + Cy-G-CSF, we used Bortezomib with G-CSF too. Hence, four different mobilization regimens were used-Bort + G-CSF (Group-1); G-CSF + Plerixafor (Group-2); Bort - Cy-G-CSF (Group-3); Cy + G-CSF (Group-4). We report here our 15-year retrospective analysis of these 4 mobilization regimens.ObjectivesPrimary objective was to determine proportion of patients with CD34+ dose ≥ 5 × 106/kg in first apheresis in various groups. Secondary objectives were to determine median CD34+ dose (×106/kg) in first apheresis, total median CD34+ dose (×106/kg) of all harvests and frequency of mobilization failure. Mobilization failure was defined as total CD34+ dose of 6/kg or abandoned harvest attempt at physician's discretion after anticipating a poor collection.ResultsAll consecutive patients with MM aged 18-65 years who underwent stem-cell mobilization from September 2007-December 2022 were included. In an intention-to-treat analysis, a total 200 patients with 205 mobilization attempts were analysed. The median age of the cohort was 48 years. The percentage of patients who collected ≥ 5 × 106 CD34+ cells/kg in the first apheresis was 26%, 53%, 69%, and 63% in Groups 1-4, respectively (p = 0.0001). The median CD34 yield in the first harvest (×106/kg) was 3.62, 5.20, 6.04, and 6.05 in Groups 1-4, respectively (p = 0.00004). The median total stem-cell dose collected (×106/kg) was 5.73, 6.17, 9.14, and 8.23 in Groups 1-4, respectively (p ConclusionCyclophosphamide-based chemo-mobilization regimens with or without Bortezomib have the advantage of higher total stem-cell yield, while they are equivalent to G-CSF + Plerixafor for harvest in a single apheresis. The addition of Bortezomib to Cyclophosphamide may help to increase stem cell yield.

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This phase 2 study evaluated the impact of pegfilgrastim, a single-dose, long-acting granulocyte colony-stimulating factor, on the steady-state mobilization of hematopoietic stem cells into peripheral blood in patients with multiple myeloma (MM) or malignant lymphoma (ML). Efficacy and safety, along with CD34-positive cell mobilization outcomes were assessed in patients with MM, who were randomly assigned to pegfilgrastim (n = 30) or daily filgrastim (n = 31), and ML (pegfilgrastim only, n = 13) cohorts. In the MM cohort, CD34-positive cell counts ≥ 2 × 106/kg were achieved in 100% of patients in the pegfilgrastim group and 96.7% in the filgrastim group (difference: 3.3%; 80% confidence interval: -0.9-7.5%), demonstrating the non-inferiority of pegfilgrastim to filgrastim. All patients in the ML cohort achieved ≥ 2 × 106/kg CD34-positive cell counts. The plerixafor administration rates in the MM cohort were 50.0% and 63.3% in the pegfilgrastim and filgrastim groups, respectively, and 91.7% in the ML cohort. There were no major differences in safety measures between the two groups. Although the sample size was small, particularly in the ML cohort, a single dose of pegfilgrastim demonstrated comparable efficacy and safety to daily doses of filgrastim, indicating its potential for clinical use while reducing patient burden.Trial Registration: jRCT2011210029, NCT05007652.

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Autologous stem cell transplantation (ASCT) is integral to treating newly diagnosed multiple myeloma (MM). While novel therapies improve response rates, they also hinder stem cell mobilization. This study evaluates the impacts of induction regimens on mobilization, collection, and ASCT outcomes. We analyzed 228 patients divided into three groups: bortezomib-thalidomide-dexamethasone (VTD, N = 117); bortezomib-lenalidomide-dexamethasone (VRD, N = 57); and daratumumab-VTD (DVTD, N = 54). Baseline characteristics showed no significant differences among the groups. Chemo-mobilization was most common in VTD (20.5%) compared to VRD (12.3%) and DVTD (5.6%). Total CD34 + cell yield (x10⁶/kg) was highest in VTD (7.1 ± 3.5) compared to VRD (5.8 ± 3.2) and DVTD (5.4 ± 2.4) [p = 0.0001]. Second mobilization was required most frequently in VRD (40.4%) compared to DVTD (24.1%) and VTD (16.2%) [p = 0.0010]. Plerixafor use was highest in VRD (40.4%) compared to DVTD (24.1%) and VTD (12.0%) [p = 0.0001]. Mobilization duration was longest in VRD (4.0 ± 1.9 days) and shortest in VTD (3.2 ± 1.7 days) [p = 0.0038]. Infused CD34 cells and platelet engraftment times were comparable among groups. Neutrophil engraftment was delayed in VRD (12.1 ± 0.9 days) compared to DVTD (11.8 ± 1.2) and VTD (11.6 ± 0.7) [p = 0.0014]. Prompt stem cell collection is essential in lenalidomide regimens to minimize mobilization challenges. While DVTD demonstrated comparable mobilization efficiency, it produced fewer CD34 cells than VTD, indicating potential challenges.

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Autologous hematopoietic stem cell transplantation is used to restore bone marrow function after high-dose chemotherapy. For apheresis, granulocyte colony-stimulating factor (G-CSF) is standard of care, but obtaining sufficient stem cells can be challenging. Other mobilization agents include plerixafor and PEGylated G-CSF (PEG-G-CSF). While efficacy of these is established in adults, limited data for their use in pediatric patients are available. Here, we compare Good versus Poor Mobilizers and study success of different mobilization regimens in regard to CD34+cell-collection, -quality, -phenotype and hematologic reconstitution in pediatric patients. In this multi-center retrospective study, we analyzed data of 278 patients with solid tumors and lymphoma, mobilized with either G-CSF (n = 224), PEG-G-CSF (n = 34), or G-CSF/PEG-G-CSF with additional plerixafor (n = 20). In Poor Mobilizers (13.7% of all patients), addition of plerixafor to G-CSF augmented CD34+cell collection, without adverse effects on hematologic reconstitution and CD34+cell quality. PEG-G-CSF-aided mobilization was successful as first-line treatment in two-thirds of patients and did not impair hematological reconstitution, compared to G-CSF-only. Within the Poor Mobilizer group, G-CSF+plerixafor increased primitive (CD45RA-CD38-CD90+CD49f+) and CXCR4-expressing CD34+cells in apheresis products compared to G-CSF-only, without exceeding levels of Good Mobilizers. No plerixafor-related increase in tumor cells was observed in apheresis products. In conclusion, our comprehensive study supports the use of plerixafor and furthermore demonstrates the potential of patient-friendly PEG-G-CSF for mobilization of pediatric patients.

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