Five-Year 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, we have treated patients with eDSA with successive infusions (first infusion: 2 g/kg, then 0.5g/kg once 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, therapeutic plasmapheresis (tPE) or immunoabsorption were added before the first IgGAM dose. The 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 March 2013 and August 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 (14–47) months.

Results: During the study period, among the 690 transplanted patients, 157 (23%) patients formed the IgGAM group and 516 (75%) the control group. Among the remaining 17 (2%) patients, 10 patients developed eDSA but were not treated and 7 were treated only with tPE and Rituximab, and thus were not considered in the result analysis.

Twenty-six (17%) IgGAM patients showed graft dysfunction concomitant with eDSA development (possible clinical AMR). Median time to eDSA development was 14 days after transplantation. Immunoabsorption or tPE were performed before the first IgGAM infusion in 64 (41%) patients. Rituximab was given after the first IgGAM dose in 122 (78%) patients. At follow-up end, treatment was completed in 133 (85%) patients (still on treatment, n=16; in-hospital deaths, n = 4; treatment interrupted earlier as intended by protocol, n = 4). In these 133 patients, IgGAM treatment cleared eDSA in 121 (91%) patients (median treatment time 3 months), 15 (12%) patients showing eDSA recurrence a median of 9 months after treatment end.

In IgGAM versus control patients and at 5-year follow-up, respectively, graft survival (%) was 70 versus 76 (p = 0.62) and freedom from CLAD (%) 84 versus 72 (p = 0.53).

Conclusion: After lung transplantation, a treatment protocol for eDSA based on IgGAM yielded high eDSA clearance. Patients with eDSA and IgGAM treatment have good 5-year graft survival similar to control patients.