Impact of reduced mycophenolate exposure on chronic lung allograft dysfunction incidence after lung transplant

Abstract

BackgroundMycophenolate mofetil (MMF) is a key immunosuppression agent for lung transplant recipients (LTR); however, the side effects often lead to dose modifications. Kidney transplant literature has shown reductions in MMF dosing led to an increased incidence of rejection, but data is limited in LTR. The objective was to evaluate the impact of reduced MMF exposure on chronic lung allograft dysfunction (CLAD) in LTR within 36 months of transplant (TXP). MethodsThis single center, retrospective cohort analyzed LTRs who had a MMF dose reduction or hold ≥ 7 days between 04/01/2016 and 10/31/2019. LTR who died ≤ 1 month from TXP were excluded. The primary outcome was incidence of CLAD 36 months from TXP compared to ISHLT registry data. Secondary outcomes were incidence of treated acute cellular rejection and characterization of MMF dose modifications. ResultsOf 109 patients evaluated, 102 (93.6%) patients had 194 MMF dose modifications within 36 months of TXP, largely due to hematologic toxicities (74.7%). Prior to modification, 142 (73.2%) were receiving MMF 1000 mg/day and 52 (26.8%) were receiving 500 mg/day. Incidence of CLAD was 36.4% at 36 months compared to 32.6% reported by ISHLT (p=0.5216). Incidence of patients with decline in FEV1> 10% was 45.1% at 36 months. ConclusionIn our cohort, most LTRs had a MMF dose modification within 36 months, yet CLAD incidence was consistent with rates reported in the ISHLT Thoracic Organ Transplant Registry. In contrast, more patients demonstrated reduced allograft function compared to post-transplant peak, consistent with ‘potential’ CLAD.