Five-Year Results of an IgA and IgM-Enriched Human Immunoglobulin G-Based Therapy for Early Anti-HLA Donor Specific Antibodies in 158 Lung-Transplanted Patients

Abstract

Purpose The development of anti-HLA donor specific antibodies early after lung transplantation (eDSA) is associated with antibody-mediated rejection (AMR) and poor graft survival. At our institution, since 2013, we have treated patients with eDSA with successive infusions (first infusion: 2gr/kg, then 0.5gr/kg every 4 weeks for a maximum of 6 months) of IgA and IgM-enriched human intravenous immunoglobulins G (Pentaglobin®, IgGAM), combined in some cases with a single dose of anti-CD20 antibody (Rituximab) and plasmapheresis (PE) or immunoabsorption. Aims of this study were to present the 5-year results of the IgGAM-based therapy and its impact on graft survival. Methods Records of patients transplanted at our institution between 03/2013 and 10/2018 were reviewed. Outcomes of patients with eDSA and treated with IgGAM (IgGAM group) and without eDSA(control group) were compared using the product-limit method of Kaplan-Meier and the log-rank test. Median (IQR) follow-up amounted to 29 (14, 48) months. Results During the study period, among the 705 transplanted patients, 158 (22%) patients formed the IgGAM group and 530 (75%) the control group. Among the remaining 17 (3%) patients, 10 patients developed eDSA but were not treated and 7 were treated only with PE and Rituximab, and thus were not considered in the study. Among the 158 IgGAM patients, 132 (84%) showed only eDSA (possible subclinical AMR) and were pre-emptively treated. The remaining 26 (16%) patients showed graft dysfunction concomitant with eDSA (possible clinical AMR). Median time to eDSA detection was 14 (11, 20) days after transplantation. As of October 2018, treatment was completed in 138 (87%) patients. IgGAM treatment cleared eDSA in 126 (91%) patients (median time 3 months), 15 (12%) patients showing eDSA recurrence at a median of 9 months after treatment end. During treatment time, freedom from biopsy-confirmed rejection (%) was 72 vs. 65 in IgGAM vs. control patients. At 5 years, graft survival (%) was 71 vs. 75 (p=0.74) and freedom from CLAD 84 vs. 70 (p=0.28) in IgGAM vs. control patients, respectively. Conclusion After lung transplantation, a IgGAM-based treatment for eDSA yielded high eDSA clearance. IgGAM patients showed improved 5-year CLAD-free survival in comparison to control patients. Graft survival was similar between groups.