To Treat or Not to Treat: DSA Positive Lung Transplant Recipients

S. Agbor-Enoh, I. Ponor, P. Shah, D. Levine, A. Cochrane, M. Philogene, J. Matthews, A. W. Brown, I. Timofte, U. Fideli, H. Kong, A. Marishta, K. Bhatti, I. Tunc, Y. Yang, H. Luikart, C. Marboe, G. Berry, A. Iacono, S. NathanK. K. Khush, J. Orens, M. Jang, H. Valantine

Research output: Contribution to journalArticle

Abstract

PURPOSE: Donor-specific antibodies (DSA) is a major risk factor for chronic lung allograft dysfunction (CLAD) after lung transplantation (LTx). Unfortunately, DSA management (Rx) varies significantly. To date, there is no accepted standard on when to initiate treatment. This study examines whether the timing of DSA treatment alters outcomes. METHODS: 435 LTx subjects enrolled in two cohort studies were included. They underwent surveillance and clinically-indicated HLA DSA testing. DSA+patients were treated with a Rituximab or Bortezomib-based regimen either before they showed any clinical or histological signs of AMR (Early Rx) or when they developed these signs of AMR (Late Rx); choice was based on provider's practice. OUTCOMES: Time from transplant to CLAD-free survival, defined as being alive and CLAD-free. CLAD was adjudicated by a committee. MEASURE: Allograft injury at time of Rx was quantified via plasma donor-derived cell-free DNA (ddcfDNA), a validated biomarker. ANALYSES: Baseline characteristics, allograft injury, DSA clearance and CLAD-free survival were compared between treatment groups and controls (DSA- patients). RESULTS: Median follow-up was 10 (IQR = 11 - 37) months. 58% of patients developed HLA DSA, which was predominantly Class II than class I (85% vs. 15%). DSA+patients were treated either early (n = 49) or Late (n = 97). The remaining 32% of DSA+patients lacked relevant clinical data or were not treated. Baseline characteristics and DSA specificities were similar between treatment groups. However, Late AMR showed higher median %ddcfDNA (4% vs 1%, p < 0.01), lower percentage of DSA clearance (40% vs 63%, p = 0.02), and a 3-fold hazard of dying or developing CLAD than Early Rx (Figure). Early Rx extended CLAD-free survival by 34 months compared to Late Rx, and showed similar CLAD-free survival as DSA-patients (p = 0.67). CONCLUSION: This study supports Early Rx of DSA over Late Rx since Early Rx shows improved CLAD-free survival. Multivariate analyses to identify other potential covariates are being planned.

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Transplantation

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    Agbor-Enoh, S., Ponor, I., Shah, P., Levine, D., Cochrane, A., Philogene, M., Matthews, J., Brown, A. W., Timofte, I., Fideli, U., Kong, H., Marishta, A., Bhatti, K., Tunc, I., Yang, Y., Luikart, H., Marboe, C., Berry, G., Iacono, A., ... Valantine, H. (2020). To Treat or Not to Treat: DSA Positive Lung Transplant Recipients. The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation, 39(4), S164. https://doi.org/10.1016/j.healun.2020.01.1118