Assessment of Antimetabolite Intolerance in Older Lung Transplant Recipients

Introduction: Adverse effects from antimetabolites often lead to therapy adjustments; older patients may be more susceptible to these effects. Project Aims: Compare the intolerance of antimetabolites between older and younger lung transplant recipients. Design: A single-center, retrospective analysis of adult lung transplant recipients transplanted between January 1, 2019 and October 31, 2021 was conducted. Patients were stratified by age at the time of transplant (≥60 or <60 years) and assessed for the first year posttransplant. The primary outcome was the incidence of antimetabolite intolerance (defined as dose adjustment, agent/formulation change, or holding/discontinuation of agent). Secondary outcomes included reason for intolerance, safety (infection and leukopenia), and efficacy (rejection and patient/graft survival). Results: One hundred and nine recipients were included; 54 in the older (≥60 years) and 55 in the younger (<60 years) cohort. Most were initiated on azathioprine (74%) posttransplant. Antimetabolite intolerance occurred in 61% of older and 53% of younger recipients (P = 0.377). The most common reasons for intolerance were leukopenia followed by gastrointestinal side effects. Biopsy-proven acute rejection occurred more often in the older cohort (39% vs 18%, P = 0.017); this no longer remained significant when controlling for induction, indication, transplant type, gender, and antimetabolite intolerance (OR 0.36, 95% CI 0.11 to 1.15). There was no difference in the incidence of leukopenia, bacterial infection, or graft/patient survival within 1 year posttransplant. Conclusion: Antimetabolite intolerance between older and younger lung transplant recipients was similar. Most required modification to the initial antimetabolite regimen due to leukopenia and gastrointestinal side effects.