Partner Therapeutics Announces Publication of a Retrospective Cohort Review of 15 LEUKINE® Treated Patients with Pediatric Malignancies and Invasive Fungal Disease Refractory to Antifungal Therapy


Lexington, MA – December 15, 2022 Partner Therapeutics, Inc. (PTx) announced publication of a single institution retrospective cohort review of 15 patients with pediatric malignancies and invasive fungal diseases that were refractory to antifungal therapy and treated adjunctively with Leukine (sargramostim; yeast-derived, glycosylated recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]).1 Additionally, the publication included a systematic review of 50 published reports of rhu GM-CSF use for invasive fungal disease. Open Forum Infectious Diseases published the manuscript entitled “Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases.” Leukine is not approved to treat invasive fungal disease.

The authors conclude: “Sargramostim may be a potential adjunctive immunomodulator for selected patients with hematological malignancies and refractory [invasive fungal diseases] IFDs.” The overall response rate for sargramostim use in the retrospective cohort was 92%. 80% of patients were refractory to antifungal therapy prior to sargramostim use. The infections were caused by Candida spp., Trichosporon sp., and molds (Aspergillus spp., Scedosporium sp), as well as the mucormycosis-causing pathogens Rhizopus sp., Lichtheimia sp.

Endogenous GM-CSF functions as a hematopoietic growth factor while also regulating the broader immune system via activation of macrophages, monocytes, and neutrophils.2 GM-CSF enhances macrophage activities such as pathogen killing and clearance as well as neutrophil fungicidal activity.3 Based on the mechanism of endogenous GM-CSF, clinicians have utilized Leukine adjunctively in treating infections, as summarized in the publication.1

The research was led by Thomas J. Walsh, MD, PhD (Hon), FIDSA, FAAM, FECMM, of the Transplantation-Oncology Infectious Disease Program at Weill Cornell Medicine and Center for Innovative Therapeutics and Diagnostics, and Tempe K. Chen, MD, of MemorialCare Miller Children’s & Women’s Hospital Long Beach and Division of Infectious Diseases at University of California Irvine School of Medicine. Dr. Walsh shared the significance of this work: “Building upon laboratory investigations of GM-CSF and pathogenic fungi that we have conducted; this paper is especially important as the translational evidence of sargramostim’s efficacy in managing invasive fungal disease in immunocompromised pediatric and adult patients. The paper imparts clinical significance to more recent preclinical data supporting the role of GM-CSF in mucosal host defenses and macrophage bioenergetics.”

Bioenergetics refers to how cells transform energy. GM-CSF signaling regulates mitochondrial bioenergetics critical to macrophage function including energy utilization, cellular metabolism, and expression of mitochondrial proteins.

Dr. Mahmoud Ghannoum, Director of Integrated Microbiome Core and Center for Medical Mycology at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center, added: “A host directed therapy such as sargramostim (Rh GM-CSF) is a promising approach to treatment of intracellular pathogens, especially in the immune compromised patient. By attempting to restore the patient’s immune processes physicians may have a new tool to combat the development of antifungal resistance.” This October, the World Health Organization (WHO) Antimicrobial Resistance Division issued a report to focus and drive policy interventions to strengthen the response to fungal infections with antifungal resistance.  The pathogens were ranked into three priority groups: critical, high, and medium.  All of the pathogens treated with Leukine in this review were due to pathogens classified as critical or high threats due to their distribution and antifungal resistance patterns.

PTx has a broad development program in place for Leukine including clinical investigations for the treatment of infectious diseases.



  1. Chen TK, Batra JS, Michalik DE, et al. Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor (rhu GM-CSF) as Adjuvant Therapy for Invasive Fungal Diseases. Open Forum Infect Dis. 2022;9(11):ofac535. doi: 10.1093/ofid/ofac535
  2. Metcalf D, Begley CG, Johnson GR, et al. Biologic properties in vitro of a recombinant human granulocyte-macrophage colony-stimulating factor. Blood. 1986;67(1):37-45. doi: 10.1182/blood.V67.1.37.37
  3. Damiani G, McCormick TS, Leal LO, Ghannoum MA. Recombinant human granulocyte macrophage-colony stimulating factor expressed in yeast (sargramostim): A potential ally to combat serious infections. Clin Immunol. 2020;210:108292. doi:10.1016/j.clim.2019.108292


LEUKINE (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast.

LEUKINE is indicated:

  • To shorten time to neutrophil recovery and to reduce the incidence of severe and life-threatening infections and infections resulting in death following induction chemotherapy in adult patients 55 years and older with acute myeloid leukemia (AML).
  • For the mobilization of hematopoietic progenitor cells into peripheral blood for collection by leukapheresis and autologous transplantation in adult patients.
  • For the acceleration of myeloid reconstitution following autologous bone marrow or peripheral blood progenitor cell transplantation in adult and pediatric patients 2 years of age and older.
  • For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older.
  • For treatment of delayed neutrophil recovery or graft failure after autologous or allogeneic bone marrow transplantation in adult and pediatric patients 2 years of age and older.
  • To increase survival in adult and pediatric patients from birth to 17 years of age acutely exposed to myelosuppressive doses of radiation (Hematopoietic Syndrome of Acute Radiation Syndrome [H-ARS]).

Important Safety Information for Leukine (sargramostim)


  • Do not administer LEUKINE to patients with a history of serious allergic reaction, including anaphylaxis, to human granulocyte-macrophage colony-stimulating factor, sargramostim, yeast-derived products, or any other component of LEUKINE.

Warnings and Precautions

  • Serious hypersensitivity reactions, including anaphylactic reactions, have been reported with LEUKINE. If a serious allergic or anaphylactic reaction occurs, immediately discontinue LEUKINE therapy, and institute medical management. Discontinue LEUKINE permanently for patients with serious allergic reactions.
  • LEUKINE can cause infusion-related reactions that may be characterized by respiratory distress, hypoxia, flushing, hypotension, syncope, and/or tachycardia. Observe closely during infusion, particularly in patients with preexisting lung disease; dose adjustment or discontinuation may be needed.
  • LEUKINE should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy.
  • Edema, capillary leak syndrome, and pleural or pericardial effusions have been reported in patients after LEUKINE administration. LEUKINE should be used with caution in patients with preexisting fluid retention, pulmonary infiltrates, or congestive heart failure. Such patients should be monitored.
  • Supraventricular arrhythmia has been reported in uncontrolled studies during LEUKINE administration, particularly in patients with a history of cardiac arrhythmia. Use LEUKINE with caution in patients with preexisting cardiac disease.
  • If absolute neutrophil count (ANC) > 20,000 cells/mm3 or if white blood cell (WBC) counts > 50,000/mm3, LEUKINE administration should be interrupted, or the dose reduced by half.  Monitor complete blood counts (CBC) with differential twice per week.
  • Discontinue LEUKINE therapy if tumor progression, particularly in myeloid malignancies, is detected during LEUKINE treatment.
  • Treatment with LEUKINE may induce neutralizing anti-drug antibodies. Use LEUKINE for the shortest duration needed.
  • Avoid administration of solutions containing benzyl alcohol (including LEUKINE for injection reconstituted with Bacteriostatic Water for Injection, USP [0.9 % benzyl alcohol]) to neonates and low birth weight infants.

Drug Interactions

  • Avoid the concomitant use of LEUKINE and products that induce myeloproliferation.Monitor for clinical and laboratory signs of excess myeloproliferative effects.

Adverse Reactions

Adverse events occurring in >10% of patients receiving LEUKINE in controlled clinical trials and reported at a higher frequency than in placebo patients are:

  • In recipients of autologous bone marrow transplantation (BMT)–asthenia, malaise, diarrhea, rash, peripheral edema, urinary tract disorder
  • In recipients of allogeneic BMT–abdominal pain, chills, chest pain, diarrhea, nausea, vomiting, hematemesis, dysphagia, GI hemorrhage, pruritus, bone pain, arthralgia, eye hemorrhage, hypertension, tachycardia, bilirubinemia, hyperglycemia, increased creatinine, hypomagnesemia, edema, pharyngitis, epistaxis, dyspnea, insomnia, anxiety, high glucose, low albumin
  • In patients with AML–fever, weight loss, nausea, vomiting, anorexia, skin reactions, metabolic laboratory abnormalities, edema



Partner Therapeutics, Inc. (PTx), an integrated biotechnology company, focuses on development and commercialization of late-stage therapeutics to improve health outcomes in treatment of cancer and other serious diseases. The company believes in delivering products and supporting medical teams with the purpose of achieving superior outcomes for patients and their families. Visit



Bill McClements

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