Axatilimab and Extracorporeal Photopheresis for the Treatment of Patients with Chronic Graft-versus-Host Disease

Inclusion Criteria

• Recipient of allogeneic hematopoietic cell transplantation (HCT)
• Age greater or equal to 12
• Chronic GVHD per 2014 NCC (Jagasia et al. 2015) or overlap syndrome requiring new therapy in patients with at least 2 prior lines of therapy, steroid refractoriness, or steroid dependence: * Prior systemic lines of therapy may include corticosteroids, calcineurin inhibitor (CNI) or sirolimus, or other systemic immunosuppressive agent such as ruxolitinib, belumosudil, or ibrutinib. GVHD prophylaxis does not count as a prior line of therapy. * Steroid refractory is defined as any of the following criteria: ** Manifestations progress despite the use of ≥ 1 mg/kg/day prednisone for at least 1 week ** Manifestations persist without improvement despite treatment with ≥ 0.5 mg/kg/day or 1 mg/kg every other day for at least four weeks. ** Recurrence after a CR, or ** Progression after a PR. * Steroid dependence is defined as inability to control cGVHD symptoms while tapering prednisone below 0.25 mg/kg/day on at least two occasions separated by at least 8 weeks. There must be evidence of clinically active cGVHD
• For patients receiving approved or commonly used agents, all GVHD systemic treatments should be discontinued except for corticosteroids and drugs being continued from GVHD prophylaxis at screening
• Eastern Cooperative Oncology Group (ECOG) performance status 0–3 as assessed at screening
• Platelet count > 50,000 platelets/μL as measured at screening
• Absolute neutrophil count > 1,000 cells/μL as measured at screening
• Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x upper limit of normal (ULN), unless attributed to presumed cGVHD as measured at screening
• Stable dose of corticosteroids for at least 14 days prior to treatment
• Sexually mature individuals must use contraception. Individuals 12 years of age and older will be considered sexually mature and must use contraception

Exclusion Criteria

• Pregnancy or breast-feeding
• Active relapse of underlying malignancy
• History or the presence of interstitial pneumonitis or drug-related pneumonitis
• Active gastrointestinal (GI) bleeding
• Inability to tolerate volume shifts associated with ECP (e.g., inadequate renal, hepatic, pulmonary and cardiac function (ejection fraction [EF] < 40%) per investigator discretion
• History of myositis
• History of splenectomy
• History of pancreatitis
• History of other malignancy (within 3 years of screening) unless treated with curative intent and approved by Principal Investigator (PI)
• Significant, uncontrolled, or active comorbid conditions or are unable to adhere to the study requirements
• Acquired Immune Deficiency Syndrome (AIDS) or active hepatitis B (Hep B) or active hepatitis C (Hep C) infection
• Prior CSF1-R targeted therapies
• Prior history of ECP treatment failure or intolerance
• Intolerance to methoxsalen, heparin, or citrate products
• Patients with aphakia due to risk of increased retinal damage or photosensitive disease (albinism, systemic lupus erythematosus, porphyria)
• Lack of stable IV access. Acceptable forms include central venous catheter, peripherally inserted central catheter (PICC), or peripheral IV line per institutional guidelines
• Insurance denial of coverage for the ECP procedure