Long-term Results of an IgM-Enriched Human Immunoglobulin-Based Therapy for Early Donor-Specific Antibodies after Lung Transplantation

Objectives: The development of anti-HLA donor specific antibodies early after lung transplantation (eDSA) has been associated with a poor graft survival. Therefore, at our institution, we have treated patients with eDSA with successive infusions (first infusion: 2 gr/kg, then 0.5 gr/kg once every 4 weeks for a maximum of 6 months) of IgM-enriched human intravenous immunoglobulins (Pentaglobin, IVIG), 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 IVIG dose. Aims of this study were to present the long-term results of the IVIG-based therapy and its impact on graft survival.

Methods: Records of patients transplanted at our institution between 03/2013 and 09/2017 were reviewed. Outcomes of patients with eDSA and treated with IVIG (eDSA/IVIG 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 24 (11–39) months.

Results: During the study period, among the 584 transplanted patients, 125 (21%) patients formed the eDSA/IVIG group and 441 (76%) the control group. Among the remaining 18 (3%) patients, 10 patients developed eDSA but were not treated and 8 were treated only with tPE and Rituximab, and thus were not considered in the following analyses. Median time to eDSA development was 14 days after transplantation. Immunoabsorption or tPE were performed before the first IVIG infusion in 36 (29%) and 16 (13%) patients, respectively. Rituximab was given after the first IVIG dose in 110 (88%) patients. At follow-up end, treatment was completed in 110 (88%) patients (still on treatment, n = 9; in-hospital deaths, n = 3; treatment interrupted earlier as intended by protocol, n = 3). In these 110 patients, IVIG treatment cleared eDSA in 103 (94%) patients (median treatment time 3 months), 12 (12%) patients showing eDSA recurrence a median of 9 months after treatment end. In eDSA/IVIG versus control patients and at 4-year follow-up, respectively, graft survival (%) was 80 versus 81 (p = 0.82), freedom (%) from biopsy-confirmed rejection 58 versus 55 (p = 0.38) and from CLAD 82 versus 81 (p = 0.85).

Conclusion: After lung transplantation, a treatment protocol for eDSA based on IVIG yielded very high eDSA clearance. Patients with eDSA and IgM-enriched IVIG-treatment have good 4-year graft survival similar to contemporary patients without eDSA.