The UK Experience of Renal Transplantation in AL Amyloidosis

Systemic AL amyloidosis, caused by monoclonal light chain depositing as amyloid fibril protein, commonly presents with renal involvement. A third of patients with renal involvement have or develop significant renal dysfunction leading to end-stage renal failure (ESRF). In an era of improving life expectancy for patients with AL amyloidosis, renal transplantation, with its marked impact on improving quality of life and reducing the cost burden, is increasingly considered. We report the outcomes of fifty patients who had received a renal allograft between 2004-2019, seen at the UK National Amyloidosis Centre

Patient characteristics were: 60% male; median age at diagnosis was 53.5 years (38-69 years); median ECOG performance status 1 (0-3); median presenting creatinine, eGFR and proteinuria were 199μmol/L (69-756 μmol/L), 27ml/min and 8.95g/24h (0.4-19.7g/24h) respectively. Involved light chains were - lambda - 36 (72%) and kappa - 14 (28%).

40 patients were evaluable (5 transplanted for non-amyloid conditions prior to diagnosis, 4 lost to follow up, 1 transplanted for amyloidosis overseas prior to referral). Thirteen (32.5%) had isolated renal involvement whilst 35 (87.5%) patients had other multi-organ involvement including 13/40 (32.5%) with cardiac involvement. Median time from diagnosis to ESRF was 15 months (0-115 months) and from renal replacement therapy to renal allograft was 28 months (3-83 months). Four (10%) received a pre-emptive renal allograft. At time of renal transplantation, patients had a median of 2 prior lines of chemotherapy (range 1-4) whilst 10/40 patients (25%) had a prior autologous stem cell transplant. At transplant, haematological responses (HR) were: complete response (CR) - 22 (55%), very good partial response (VGPR) - 12 (30%), partial response (PR) - 4 (10%) and stable disease - 2 (5%). Median time from HR to renal transplant was 29 months (0-93 months). From renal transplant, haematological PFS was 82.7 months (95% CI 61.2-104.2). Patients achieving a CR achieved a markedly higher PFS of 102.5 months (95% CI 68.8-136.3 months) (p=0.023) as did those with a dFLC <10mg/L at renal transplantation, 121.1 months (95% CI 91.5-150.6 months) (p=0.0001).

At a median follow up of 107 months (26-231 months), 14 (35%) patients died, of whom only one had graft failure at the time of death. One patient (with stage 3 cardiac AL) died within 2 days of a renal allograft after a post-operative hypotensive episode. Nine (22.5%) patients had post-transplant chemotherapy for relapse. Median OS from renal transplantation was 106.6 months (95% CI 85.0-128.3 months); significantly better in patients achieving a CR (133.0 months, p=0.005) or dFLC <10mg/L (137.8 months, p=0.0001) prior to transplant. Stage of chronic kidney disease at presentation, plasma cell burden, age at renal transplantation and multi-organ involvement did not impact overall survival. Of the patients experiencing graft failure, 1 graft failed within a week of implantation due to primary non-function after a prolonged cold ischaemia time, 1 functioned poorly from implantation and failed within 4 months and a third failed after 45 months with evidence of amyloid recurrence in the graft.

In conclusion, the outcomes of carefully selected patients with AL amyloidosis undergoing renal transplantation is promising and justifies careful consideration. There was only 1 peri-operative death. Patients in a complete response or who have a dFLC <10mg/L prior to renal allograft implantation have significantly better outcomes. At a median follow ~9 years, graft failure is rare (only 7.5%).