Lexington, MA – January 17, 2024 – Partner Therapeutics, Inc. (PTx) announced today the publication of a comprehensive review by Mora et al. in the International Journal of Cancer which summarizes the efficacy and safety of anti-GD2 monoclonal antibodies (mAbs) (dinutuximab, dinutuximab beta, and naxitamab) in children with high-risk neuroblastoma when given in combination with Leukine (sargramostim; glycosylated, yeast-derived recombinant human granulocyte-macrophage colony-stimulating factor [rhu GM-CSF]), recombinant human granulocyte colony-stimulating factor (G-CSF) or no cytokine.1
The review provides a succinct summary of the mechanistic rationale and clinical data supporting the use of Leukine in combination with anti-GD2 mAbs. It also describes why the authors believe it is suboptimal to replace with Leukine with G-CSF in this regimen for mechanistic reasons.
Leukine has been studied extensively in combination with dinutuximab and naxitamab leading to improved patient outcomes. As a result, all clinical trials supporting the FDA-approval of dinutuximab and naxitamab included Leukine and both products are labeled for use in combination with GM-CSF.
“The pleiotropic effects of Leukine contribute to its important role as an immunomodulatory adjuvant in combination with anti-GD2 mAbs,” noted Jaume Mora, M.D., Ph.D., Scientific Director of Oncology and Hematology at Sant Joan de Déu Barcelona Children’s Hospital and lead author of the publication. “GM-CSF stimulates neutrophils and macrophages leading to increased cellular phagocytosis and increased ADCC. Further, GM-CSF increases major histocompatibility complex (MHC) class II expression which enhances tumor antigen presentation on dendritic cells that can mediate T cell antitumor effects. For all of these mechanistic reasons, Leukine is a critical component of anti-GD2 therapy.” The figure below from the publication depicts these mechanisms.
1Mora J, Modak S, Kinsey J, Ragsdale CE, Lazarus HM. GM-CSF, G-CSF or no cytokine therapy with anti-GD2 immunotherapy for high-risk neuroblastoma. Int J Cancer. 2023 Dec 18. doi: 10.1002/ijc.34815.
LEUKINE (sargramostim) is a glycosylated recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) produced by recombinant DNA technology in yeast. The product is commercially available in the United States and accessible through a named patient program operated by Tanner Pharma Group outside of the United States.
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 two years of age and older.
- For the acceleration of myeloid reconstitution following allogeneic bone marrow transplantation in adult and pediatric patients two 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 two 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 [HARS]).
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.
- Avoid the concomitant use of LEUKINE and products that induce myeloproliferation. Monitor for clinical and laboratory signs of excess myeloproliferative effects.
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
ABOUT PARTNER THERAPEUTICS
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 www.partnertx.com.