Lenalidomide and dexamethasone in relapsed/refractory immunoglobulin light chain (AL) amyloidosis: results from a large cohort of patients with long follow-up

Lenalidomide and dexamethasone (RD) is a standard treatment in relapsed/refractory immunoglobulin light chain (AL) amyloidosis (RRAL). We retrospectively investigated toxicity, efficacy and prognostic markers in 260 patients with RRAL. Patients received a median of two prior treatment lines (68% had been bortezomib-refractory; 33% had received high-dose melphalan). The median treatment duration was four cycles. The 3-month haematological response rate was 31% [very good haematological response (VGHR) in 18%]. The median follow-up was 56 center dot 5 months and the median overall survival (OS) and haematological event-free survival (haemEFS) were 32 and 9 months. The 2-year dialysis rate was 15%. VGHR resulted in better OS (62 vs. 26 months, P < 0 center dot 001). Cardiac progression predicted worse survival (22 vs. 40 months, P = 0 center dot 027), although N-terminal prohormone of brain natriuretic peptide (NT-proBNP) increase was frequently observed. Multivariable analysis identified these prognostic factors: NT-proBNP for OS [hazard ratio (HR) 1 center dot 71; P < 0 center dot 001]; gain 1q21 for haemEFS (HR 1 center dot 68, P = 0 center dot 014), with a trend for OS (HR 1 center dot 47, P = 0 center dot 084); difference between involved and uninvolved free light chains (dFLC) and light chain isotype for OS (HR 2 center dot 22, P < 0 center dot 001; HR 1 center dot 62, P = 0 center dot 016) and haemEFS (HR 1 center dot 88, P < 0 center dot 001; HR 1 center dot 59, P = 0 center dot 008). Estimated glomerular filtration rate (HR 0 center dot 71, P = 0 center dot 004) and 24-h proteinuria (HR 1 center dot 10, P = 0 center dot 004) were prognostic for renal survival. In conclusion, clonal and organ biomarkers at baseline identify patients with favourable outcome, while VGHR and cardiac progression define prognosis during RD treatment.