Six-Year Clinical Results of an IgA-and IgM-Enriched Human Immunoglobulin-Based Therapy for Early Anti-HLA Donor Specific Antibodies after 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, patients with eDSA were treated with successive infusions (first infusion: 2 g/kg, then 0.5 g/kg once in every 4 weeks for a maximum of 6 months) of IgA- and IgM-enriched human intravenous immunoglobulins (Pentaglobin, 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.

Methods: Records of patients transplanted at our institution between February 2013 and August 2019 were reviewed. Outcomes were compared between patients with eDSA and treated with IgGAM (IgGAM group) and without eDSA (control group). Median (IQR) follow-up was 34 (range: 14–55) months.

Results: During the study period, among the 808 transplanted patients, 183 (23%) patients formed the IgGAM group and 604 (75%) the control group. The remaining 21 (2%) patients (12 patients with eDSA but not treated, and 9 patients treated only with tPE and Rituximab) were excluded. Thirty-three (18%) IgGAM patients showed graft dysfunction concomitant with eDSA development. Median time to eDSA development was 14days after transplantation. Immunoabsorption or PE were performed before the first IgGAM infusion in 71 (39%) patients. Rituximab was given after the first IgGAM dose in 130 (71%) patients. At follow-up end, treatment was completed in 166 (91%) patients (still on treatment, n = 6; in-hospital deaths, n = 4; treatment interrupted earlier as intended by protocol, n = 7). In these 166 patients, IgGAM treatment cleared eDSA in 149 (90%) patients, 22 (15%) 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 6-year follow-up, respectively, graft survival (%) was 72 versus 73 (p = 0.67) and freedom from CLAD 70 vs. Sixty-three (p = 0.47). Graft and CLAD-free survival did not differ between IgGAM patients with and without graft dysfunction (p = 0.56 and p = 0.34).

Conclusion: After lung transplantation, a treatment protocol for eDSA based on IgGAM yielded high eDSA clearance. Patients with eDSA and IgGAM-treatment have good 6-year graft survival similar to control patients.

No conflict of interest has been declared by the author(s).