Combination Therapy With Carfilzomib for the Antibody-Mediated Rejection Diagnosis in Lung Transplantation

The main objective of the proposed clinical investigation is to evaluate the effects of carfilzomib in addition to conventional therapy on short-term outcomes after the diagnosis of antibody-mediated rejection in lung transplant recipients. In this study, Carfilzomib will be administered at a dose of 20 mg/m2 on two consecutive days, each week for three weeks (Days 1 2, 8, 9, 15, and 16) to constitute one therapeutic cycle. Carfilzomib may be administered for 1-2 complete cycles in the study. Patients will be followed for the duration of their hospital admission after enrollment. Post treatment follow-up will also occur on Days 42 and 90.

Inclusion criteria

• Adult lung transplant recipients ≥ 18 years of age who meet the diagnostic criteria for AMR and who have underwent PFT testing unless intubated and transbronchial biopsy prior to enrollment.

Exclusion criteria

• Direct contraindications or previous intolerances to any component of the standard of care regimen including PLEX, 5% human albumin, 5% gammagard S/D or 10% gammagard liquid
• Leukopenia
• Neutropenia
• Thrombocytopenia
• Known Child-Pugh B/C cirrhosis
• Total bilirubin > 4
• ALT > 90
• Known systolic heart failure with LVEF < 40%
• Known pulmonary hypertension
• Any uncontrolled comorbid condition
• Pregnant women
• Breastfeeding women
• Ongoing bacterial or fungal or viral infection that is life-threatening
• Active cytomegalovirus disease
• Active varicella zoster infection
• Previous intolerance to carfilzomib
• Concurrent use of another proteasome inhibitor (e.g., bortezomib)