The authors describe the mechanisms underlying GI irAEs and their similarities to inflammatory bowel disease and review the available clinical data supporting a potential role for Leukine in both settings. In the prospective, randomized study E1608, Hodi and colleagues2 observed that advanced melanoma patients who received Leukine plus ipilimumab had a reduction in GI irAEs (p=0.05) (see figure below) as well as a significant improvement in overall survival (p=0.01) compared to those who received ipilimumab alone. "Immune checkpoint inhibitors have meaningfully improved prognoses for cancer patients in a number of cancers," said Michael Dougan MD, PhD, Associate Professor of Medicine at Massachusetts General Hospital. "Unfortunately, these drugs also can cause the immune system to attack healthy cells creating unwanted GI side effects including some that lead to discontinuation of treatment and more severe outcomes. The potential Leukine has shown in mitigating GI irAEs and improving patient outcomes, including survival, are encouraging." Leukine continues to be studied in combination with ICIs to assess differences in the rate of serious adverse events as well as its impact on overall survival. "The phase 2 portion of study EA6141 was completed previously, and after a successful planned interim analysis, advanced to the phase 3 portion, which is now in the last stages of enrollment," said Dr. Hodi in a recent statement. "The primary objective is to compare the overall survival rates of patients who receive nivolumab/ipilimumab/rhu GM-CSF versus those who receive only nivolumab/ipilimumab." National Cancer Institute. A Phase II/III Trial of Nivolumab, ipilimumab, and GM-CSF in patients with advanced melanoma. Available at: https://clinicaltrials.gov/ct2/show/NCT02339571. NLM identifier: NCT02339571. Accessed April 16, 2024. Melanoma is the most aggressive form of skin cancer and rates of melanoma have been rising for the past 30 years. The American Cancer Society estimates 96,480 new melanoma cases will be diagnosed in the US and 7,230 people will die from the disease in 2019. The FDA grants orphan drug designation to promote the development of promising treatments for conditions that affect 200,000 or fewer U.S. patients annually. 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. LEUKINE should not be administered simultaneously with or within 24 hours preceding cytotoxic chemotherapy or radiotherapy or within 24 hours following chemotherapy. 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. 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 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 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