Partner Therapeutics Announces Publication of 30-month Randomized Open Label Study of LEUKINE® in Combination with Whole Lung Lavage for Treatment of Autoimmune Pulmonary Alveolar Proteinosis (aPAP)

89% (8/9) of Patients Taking Inhaled Leukine Did Not Require Further Whole Lung Lavage in the 30-month Period

LEXINGTON, Mass., Nov. 30, 2023 /PRNewswire/ — Partner Therapeutics, Inc. (PTx) announced today that the European Respiratory Journal published the results of a prospective, randomized clinical trial of Leukine in patients with moderate to severe autoimmune pulmonary alveolar proteinosis (aPAP) (DOI: 10.1183/13993003.01233-2023).

aPAP is a progressive lung disorder driven by blockage of GM-CSF signaling due to the production of GM-CSF autoantibodies. The deficiency of GM-CSF in aPAP patients inhibits the ability of these patients to differentiate monocytes into alveolar macrophages, which causes aPAP patients to accumulate surfactant in their lungs.  This leads to low oxygen levels, difficulty breathing, innate immune deficiency, and in some cases, serious infection, pulmonary fibrosis, respiratory failure, and death.

This newly published study enrolled 18 patients, all of whom received bilateral whole lung lavage (WLL), a widely accepted palliative therapy for aPAP. Patients were then randomized to receive inhaled Leukine (sagramostim, rhu GM-CSF) or no treatment. Patients were followed for 30 months.

The study met its primary endpoint of time to first rescue WLL. One patient out of 9 (11%) treated with Leukine required a WLL during the 30-month period. Seven of 9 (78%) patients who did not receive Leukine required a WLL (p=0.0078). The median time to WLL in the control group was 18 months. Patients in the Leukine arm also showed greater improvement in markers of lung function (PaO2, A-aDO2, DLco% and aPAP biomarkers). Leukine was well tolerated and adverse events were comparable across arms. Leukine is FDA approved for six indications; it is not approved for aPAP.

First author, Ilaria Campo, PhD of Pneumology Unit at Fondazione IRCCS Policlinico San Matteo in Pavia, Italy, notes, “The significant difference in need for WLL between groups over a prolonged period is clinically meaningful. WLL is an invasive procedure that washes surfactant out of the lungs; it requires hospitalization, general anesthesia, and mechanical ventilation. Patients who are quick surfactant accumulators can require WLL as frequently as every month while the median rate of lavage for those with moderate to severe disease is about 18 months. WLL provides immediate therapeutic benefit to patients by removing built up surfactant, but it does not slow or stop surfactant accumulation or correct alveolar macrophage dysfunction, which it appears Leukine is doing.”

“This clinical study showed that Leukine significantly increased the interval between lavage procedures,” noted Bruce Trapnell, MD, Professor of Medicine and Pediatrics at the University of Cincinnati, and Director, Translational Pulmonary Science Center Cincinnati Children’s Hospital Medical Center.  “These results indicate that in patients with moderate to severe aPAP, whole lung lavage can act as an induction therapy to reset the patient’s baseline surfactant level while a targeted pharmacologic therapy, like Leukine, may then be able to address the underlying pathophysiology of the disease. Further study of Leukine immediately following whole lung lavage is warranted to confirm these results.”

Professor, Doctor Maurizio Luisetti designed this study but tragically died while it was underway. The study continued under the leadership of Dr. Campo and Dr. Francesca Mariani of Pneumology Unit at Fondazione IRCCS Policlinico San Matteo in Pavia, Italy. Partner Therapeutics is grateful to Professor Luisetti, the entire study team, and the patients who participated in the study for their tireless commitment to the PAP community. Funding for the study was provided by Agenzia Italiana del Farmaco (AIFA).


1.  Seymour JF, Presneill JJ. Pulmonary alveolar proteinosis: progress in the first 44 years. Am J Respir Crit Care Med. 2002 Jul 15;166(2):215-35. doi: 10.1164/rccm.2109105. PMID: 12119235.


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