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Immunomodulatory Therapies
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Sargramostim (Leukine™) is a recombinant Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) product that functions as an immunostimulator primarily used for myeloid reconstitution after autologous or allogeneic bone marrow transplantation. It is also used to treat neutropenia induced by chemotherapy during the treatment of acute myeloid leukemia. This agent was approved by the FDA in 1991, although in early 2008 the manufacturer (Bayer) informed healthcare professionals that the liquid formulation of sargramostim would be withdrawn. This was due to an upward trend in reported adverse reactions, including fainting, which appeared to be associated with a change made to the formulation in April 2007 involving the inclusion of disodium edetate (EDTA). These additional adverse reactions had not been observed with the previous lyophilized formulation of sargramostim, and so this original formulation was returned to the market in the US in May 2008. In 2009, Genzyme acquired the rights to LeukineTM from Bayer.
In Situ Gene Insertion for Immunotherapy Using Vaccinia Virus Vectors
Published in Eric Wickstrom, Clinical Trials of Genetic Therapy with Antisense DNA and DNA Vectors, 2020
Edmund C. Lattime, Laurence C. Eisenlohr, Michael J. Mastrangelo
GM-CSF is a multilineage stimulating factor (Sieff et al., 1985) for granulocytes, macrophages, megakaryocytes, erythroid colonies and Β and Τ lymphocytes. Costello (1993) reviewed the therapeutic use of GM-CSF. Sargramostim® is a recombinant yeast-derived form of GM-CSF that has been approved for use in myeloid reconstitution after autologous bone marrow transplantation. The recommended dose (Physician's Desk Reference, 1993) is 250 μg/m2/day x 21 days. The maximum tolerated dose has not been determined, as toxicity is modest.
Sargramostim in acute radiation syndrome
Published in Expert Opinion on Biological Therapy, 2022
Hillard M Lazarus, John McManus, Robert Peter Gale
‘When human efficacy studies are not ethical and field trials are not feasible, FDA may rely on adequate and well-controlled animal efficacy studies to support approval of a drug or licensure of a biological product under the Animal Rule’ [44]. We base our recommendations for the use of sargramostim in nuclear and radiation accidents on biologic considerations including the growth of myeloid cells in vitro, on data from adequate and well-controlled animal efficacy studies, and on data in humans in other settings of severe myelosuppression. As noted above, approval for filgrastim and pegfilgrastim was based on animals receiving blood transfusions, unlikely after nuclear and radiation accidents. Further, we note the added benefit for sargramostim lowering mortality even if given later after exposure than for filgrastim and pegfilgrastim that required administration within 24 h.
Colony stimulating factors for prophylaxis of chemotherapy-induced neutropenia in children
Published in Expert Review of Clinical Pharmacology, 2022
Sargramostim can be given either as IV infusion or SC injection. The mean area under the time-concentration curve (AUC0-inf) for IV infusion was 32.9 ng h/mL and ANC0-24 of SC administration was 21.3 ng h/mL [24]. The absolute bioavailability with SC administration was 75% of IV infusion. Half-life of sargramostim given as IV infusion over two hours is approximately twice of drug given by SC injection. Specific metabolism studies were not conducted since sargramostim is a protein and is expected to degrade to small peptides and amino acids. There are no dosage adjustments provided in the manufacturer’s labeling. The use of sargramostim for pediatric patients for neutrophil recovery following induction chemotherapy has not been well evaluated yet. Safety and efficacy of sargramostim for pediatric patients 2 years or older for bone marrow transplantation, treatment of delayed neutrophil recovery, or graft failure have been studied. Weight-based dosing is available only for pediatric patients who were acutely exposed to myelosuppressive doses of radiation [24].
Spaceflight medical countermeasures: a strategic approach for mitigating effects from solar particle events
Published in International Journal of Radiation Biology, 2021
Sargramostim (Leukine®, Partner Therapeutics) is a recombinant human granulocyte macrophage colony stimulating factor (GM-CSF) which stimulates proliferation and differentiation of hematopoietic progenitor cells to divide and differentiate into neutrophils, monocytes, macrophages and myeloid-derived dendritic cells, and it is also capable of activating mature granulocytes and macrophages. Leukine® is FDA approved to be used clinically for treatment of neutropenia following chemotherapy similar to Neupogen® and Neulasta®. As a result of substantial support from BARDA, it recently received FDA approval (FDA 2018) to increase survival in adult and pediatric patients acutely exposed to myelosuppressive doses of radiation. Prescribing information for Leukine® indicates it should be delivered daily and continued until an absolute neutrophil count (ANC) >1000 cells/mm3 is maintained for 3 consecutive days. Leukine® (250 mcg) is available in a lyophilized (freeze-dried) form, that is reconstituted with 1.0 mL of bacteriostatic water for injection, USP (0.9% benzyl alcohol) making it attractive for storage and stability on long duration missions.