Seven-Year Clinical Results of AN IgA- and IgM-Enriched Human Immunoglobulin-Based Therapy for Antibody-Mediated Rejection in Lung Transplantation

Objectives: The development of anti-HLA donor-specific antibodies early after lung transplantation (eDSA) has been associated with antibody-mediated rejection (AMR) and poor graft survival. At our institution, since 2013, successive infusions of IgA- and IgM-enriched human intravenous immunoglobulins (IgGAM, first infusion: 2 g/kg, then 0.5 g/kg once every 4 weeks for a maximum of 6 months) formed the backbone of eDSA therapy. Actually, patients with only evidence of eDSA (possible subclinical AMR) are treated with IgGAM only. Patients with concomitant graft dysfunction (possible clinical AMR) or positive virtual and CDC crossmatch receive additionally plasmapheresis (PE) or immunoabsorption before the first IgGAM dose, and a single dose of anti-CD20 antibody (Rituximab) thereafter. Aim of this study was to present the 7-year results of the IgGAM-based therapy.

Methods: Records of patients transplanted at our institution between 02/2013 and 08/2020 were reviewed. Outcomes were compared between patients with eDSA treated with IgGAM (IgGAM group) and without eDSA (control group). Median (IQR) follow-up was 40 (18–63) months.

Result: During the study period, among the 896-transplanted patients, 218 (24%) patients formed the IgGAM group and 657 (73%) the control group. The remaining 21 (3%) patients (12 patients with eDSA but not treated, and 9 patients treated only with tPE and Rituximab) were excluded. Forty-one IgGAM patients (19%) showed preformed eDSA, 36 (17%) patients showed graft dysfunction, and 16 (7%) patients showed a positive crossmatch. Median time to eDSA detection was 14 days after transplantation. At follow-up end, treatment was completed in 197 (90%) patients (still on treatment, n = 8; in-hospital deaths, n = 4; treatment interrupted earlier as intended by protocol, n = 9). In these 197 patients, IgGAM treatment cleared eDSA in 178 (90%) patients, 24 (12%) patients showing eDSA recurrence a median of 9 months after treatment end. Clearance was worse in patients with preformed eDSA (p < 0.001). In IgGAM versus control patients and at 7-year follow-up, respectively, graft survival (%) was 72 versus 70 (p = 0.86) and freedom from CLAD was 69 versus 65 (p = 0.63). Graft and CLAD-free survival did not differ between IgGAM patients with and without graft dysfunction.

Conclusion: After lung transplantation, a treatment protocol for eDSA based on IgGAM yielded high eDSA clearance. Patients with eDSA and IgGAM treatment have good 7-year graft survival similar to control patients.

Publication History

Article published online:
19 February 2021