Therapeutic Drug Monitoring-Guided Combination Alemtuzumab and Plasmapheresis for Refractory Acute Lung Allograft Dysfunction Rescue Therapy

Abstract

<h3>Introduction</h3> Alemtuzumab is a potent immunosuppressive that has been used for treatment of refractory acute lung allograft dysfunction (ALAD); however, its use in combination with plasmapheresis (PP) after lung transplantation has not been described. <h3>Case Report</h3> A 35 year old female underwent bilateral lung transplantation for WHO group 1 pulmonary arterial hypertension secondary to limited scleroderma. Induction consisted of basiliximab and steroids, initial maintenance included steroids, mycophenolate and tacrolimus. Post operative day (POD) 5 she developed progressive respiratory failure requiring VV-ECMO support. Infectious and HLA DSA workup were negative; however, CT and bronchoscopic findings were suggestive of antibody mediated rejection (AMR). A presumptive diagnosis of non-HLA AMR was made. Treatment consisted of PP, ATG, IVIg and rituximab. After transient improvement, on POD 47 a second course of ATG and steroid pulse with taper was required due to progressive ALAD. By POD 66 there was further deterioration of graft function. Alemtuzumab rescue was administered with PP for elimination of effector immune cells and treatment of presumed persistent non-HLA AMR. In the absence of PP alemtuzumab is known to exceed concentrations that inhibit reconstitution (>0.7 ug/mL) for several weeks. To ensure PP did not impair prolonged cytoreduction, or alemtuzumab-induced tolerogenicity, plasma monitoring of alemtuzumab was used to allow for redosing if the level fell below 0.7 ug/mL after PP. Elimination was not significantly altered after redosing (figure 1). Her ALAD stabilized although she developed severe restrictive CLAD. There were no infectious complications. 153 days following alemtuzumab administration, after completing inpatient prehabilitation, she was successfully retransplanted. <h3>Summary</h3> Therapeutic drug monitoring can be used to safely readminister alemtuzumab when used in combination with PP for rescue of refractory ALAD.