Steroid Sparing Maintenance Immunosuppression in Highly Sensitised Patients Receiving Alemtuzumab Induction

Abstract

This analysis reports on the outcomes of two different steroid sparing immunosuppression protocols used in the management of 120 highly sensitised patients (HSPs) with cRF>85% receiving Alemtuzumab induction, 53 maintained on tacrolimus (FK) monotherapy and 67 tacrolimus plus mycophenolate mofetil (FK + MMF). There was no difference in the median cRF or mode of sensitisation between the two groups, although the FK + MMF cohort received more poorly matched grafts. There was no difference in one-year patient or allograft survival, however rejection free survival was inferior with FK monotherapy compared with FK + MMF at 65.4% and 91.4% respectively, p < 0.01. DSA-free survival was comparable. Whilst there was no difference in rates of BK between the cohorts, CMV-free survival was inferior in the FK + MMF group at 86.0% compared with 98.1% in the FK group, p = 0.026. One-year post-transplant diabetes free survival was 89.6% and 100.0% in the FK and FK + MMF group respectively, p = 0.027, the difference attributed to the use of prednisolone to treat rejection in the FK cohort, p = 0.006. We report good outcomes in HSPs utilising a steroid sparing protocol with Alemtuzumab induction and FK + MMF maintenance and provide granular data on immunological and infectious complications to inform steroid avoidance in these patient groups.

Keywords: Alemtuzumab; HLA; calculated reaction frequency; highly sensitised; steroid sparing.

FIGURE 1

Highly sensitised (cRF≥85%) recipients transplanted between 2014 and 2022 by immunosuppression regimen.

FIGURE 2

Clinical outcomes associated with and without the use of mycophenolate in highly sensitised patients (A) All-cause 1 year allograft survival was 92.5% and 83.8% in the FK and FK + MMF groups respectively, p = 0.17 (log-rank) (B) Death censored allograft survival was 94.3% and 89.6% in the FK and FK + MMF groups respectively, p = 0.40 (log-rank) (C) One-year rejection free survival was inferior in the FK cohort compared with the FK + MMF cohort at 65.4% and 91.4% respectively, p = 0.0005 (log-rank) (D) One-year DSA free survival was 80.6% and 80.6%, in the FK and FK + MMF cohort respectively, p = 0.90 (log-rank).

FIGURE 3

One-year rejection free survival by immunological characteristics (log-rank) One-year rejection free survival (log-rank) was (A) No difference by cRF status, p = 0.57 (B) No difference by mode of sensitisation, p = 0.74 (C) No difference in patients receiving a >2nd graft by presence or absence of repeat HLA mismatch, p = 0.08 (D) No difference by HLA matchability, p = 0.79 (E) No difference by UKT Level Mismatch, p = 0.77 (F) Inferior in patients who received a post-transplant blood transfusion, p = 0.045.

FIGURE 4

One-year DSA free survival by immunological characteristics One-year DSA free survival (log-rank) was (A) No difference by cRF status, p = 0.37 (B) No difference by mode of sensitisation, p = 0.82 (C) No difference in patients receiving a >2nd graft by presence or absence of repeat HLA mismatch, p = 0.12 (D) No difference by HLA matchability, p = 0.66 (E) No difference by UKT Level Mismatch, p = 0.85 (F) Inferior in patients who received a post-transplant blood transfusion, p = 0.078.

FIGURE 5

Adverse clinical outcomes associated with and without the use of mycophenolate in highly sensitised patients At one-year post-transplant, there was (A) No difference in BK-virus free survival between the FK and FK + MMF groups, p = 0.41 (B) Superior CMV free survival in the FK group compared with the FK + MMF group, p = 0.026 (C) Inferior PTDM free survival in the FK group compared with the FK + MMF group, p = 0.027 (D) Inferior prednisolone free survival in the FK group compared with the FK + MMF group, p = 0.006.