Anti-Thymocyte Globulin as a Therapy for Chronic Lung Allograft Dysfunction: A Single-Center Experience

Anti-thymocyte globulin (ATG) is a polyclonal antibody formulation which has been used as a second-line therapy for chronic lung allograft dysfunction (CLAD). Limited data exist evaluating its efficacy; however, several single-center retrospective studies have variably demonstrated either improvement or stabilization of spirometry parameters after administration of ATG. ATG has been in use at UT Southwestern for treatment of CLAD since at least 2010; here, we seek to evaluate the effectiveness of this intervention at our center.  METHODS: A retrospective chart review was conducted of a total of 136 patients who underwent lung transplantation at UT Southwestern Medical Center between 2010 and 2022. Of these, 72 patients had received ATG specifically for treatment of CLAD, and the remaining 64 had never received ATG. Two separate analyses were performed: in the first, among those who received ATG for CLAD, spirometry data from the 6 months preceding and following ATG administration were reviewed and rates of change in FEV1 were calculated for each time period. Descriptive statistics were performed to summarize the baseline clinical characteristics and outcomes after ATG, with patients classified as having either a full response (positive rate of change in FEV1) or partial response (>20% attenuation in rate of FEV1 decline) to ATG.  In the second analysis, survival was described among those who received ATG for CLAD and comparison was provided between propensity-score matched cohorts from the ATG and non-ATG groups.

Of the 63 patients who received ATG for treatment of CLAD (and had adequate spirometry measurements available to trend FEV1), 49 (77.8%) had at least a partial response to therapy; 8 (12.7%) experienced an overall improvement in FEV1. Response to ATG was found to be associated with a more rapid rate of pre-ATG decline in FEV1; no other baseline parameters were found to be predictive of a response to ATG. Median post-CLAD graft survival was 31.7 months among those who received ATG, and only baseline absolute neutrophil count was found to be associated with worse post-CLAD graft survival among this group.

Anti-thymocyte globulin therapy, when given for CLAD, was associated with at least a modest attenuation in rate of FEV1 decline in most patients but only rarely preceded an absolute improvement in FEV1. Further study is warranted to better define the role for ATG in treatment of CLAD, a challenging disease state with limited therapeutics available.