Six-Year Results of an IgA- and IgM-Enriched Immunoglobulin-Based Therapy for Early Detectable Anti-HLA Donor Specific Antibodies in Lung Transplantation

Abstract

The development of early detectable anti-HLA donor specific antibodies after lung transplantation (eDSA) has been associated with antibody-mediated rejection (AMR) and poor graft survival. At our institution, eDSA patients were treated with successive infusions (first infusion: 2g/kg, then 0.5g/kg once every 4 weeks for a maximum of 6 months) of IgA- and IgM-enriched human intravenous immunoglobulins (IgGAM), usually combined with a single dose of anti-CD20 antibody (Rituximab) since 2013. In some cases, plasmapheresis (PE) or immunoabsorption were added before the first IgGAM dose. Aims of this study were to present the 6-year results of the IgGAM-based therapy. Records of patients transplanted at our institution between 02/2013 and 09/2019 were reviewed. Outcomes were compared between patients with eDSA and treated with IgGAM and patients without eDSA (control group). Median follow-up was 35 (16-56) months. During the study period, among the 816 transplanted patients, 186 (23%) patients formed the IgGAM group and 609 (75%) the control group. The remaining 21 (2%) patients (12 patients with eDSA but not treated, and 9 patients treated only with PE and Rituximab) were excluded. eDSA developed at a median of 14 days after transplantation. Thirty-four (18%) IgGAM patients showed graft dysfunction at the same time with eDSA detection (possible clinical AMR). Immunoabsorption/PE were performed in 71 (38%) patients and Rituximab was given to 132 (71%) patients. Treatment was completed in 167 (90%) patients (still on treatment, n=8; in-hospital deaths, n=4; treatment interrupted earlier as per protocol, n=7). In these 167 patients, IgGAM treatment cleared eDSA in 150 (90%) patients, 23 (15%) patients showing eDSA recurrence at a median 9months after treatment end. Clearance was worse in patients with preformed eDSA (p<0.001). In IgGAM vs control patients and at 6-year follow-up, respectively, graft survival (%) was 72 vs. 75 (p=0.58) and freedom from CLAD (%) 72 vs. 65 (p=0.36). Graft and CLAD-free survival did not differ between IgGAM patients with and without graft dysfunction (p=0.66 and p=0.37). After lung transplantation, a treatment based on IgGAM yielded high eDSA clearance. Patients with eDSA and IgGAM treatment have good 6-year graft survival similar to control patients.