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

Abstract

Background: Mycophenolate 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 are 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). Methods: This single-center, retrospective cohort analyzed LTRs who had an MMF dose reduction or hold ≥7 days between April 1, 2016 and October 31, 2019. LTR who died ≤1 month from TXP were excluded. The primary outcome was incidence of CLAD 36 months from TXP compared to the International Society for Heart and Lung Transplantation (ISHLT) registry data. Secondary outcomes were incidence of treated acute cellular rejection and characterization of MMF dose modifications. Results: Of 109 patients evaluated, 102 (93.6%) patients had 194 MMF dose modifications within 36 months of TXP, largely due to hematologic toxicities (74.7%). Before modification, 142 (73.2%) were receiving MMF 1,000 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 forced expiratory volume in 1 sec ≥10% was 45.1% at 36 months. Conclusions: In our cohort, most LTRs had an 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-TXP peak, consistent with “potential” CLAD.

Keywords

• lung transplant
• mycophenolate
• rejection
• CLAD
• immunosuppression