PB2138 LIGHT CHAIN (AL) AMYLOIDOSIS: A SINGLE CENTRE EXPERIENCE AND THE EFFECTIVENESS OF BORTEZOMIB BASED THERAPY AS FIRST LINE THERAPY

Abstract

Background:Amyloidosis is a heterogenous disease characterised by deposition of amyloid fibrils in soft tissue. Light chain (AL) amyloidosis is the most common form of systemic amyloidosis and is a complication of plasma cell dyscrasia. It can affect a wide range of organs including kidneys, heart, nervous system, liver, gastrointestinal tract and spleen which make the diagnosis difficult. Kidneys are the most commonly affected organ in AL amyloidosis and most patients present with nephrotic range proteinuria.In light chain amyloidosis, clonal plasma cells use proteasome to cope with misfolded light chain induced proteotoxicity, and the proteasome inhibitor bortezomib is a potential targeted therapy. Studies have demonstrated that Cyclophosphamide, Bortezomib, Dexamethasone (CyBorD) is a useful, highly effective upfront option.Aims:A retrospective study to evaluate the experience of a single centre, Waitemata District Health Board on the source of referral, biopsy source and the effectiveness of Bortezomib‐based therapy with long term follow up.MethodsDatabase at Waitemata District Health Board was searched for newly diagnosed patients with amyloidosis between 2001 and 2018. 55 out of 70 cases reported to New Zealand Cancer Registry were included. The source of referral, light chain subtype, disease association and biopsy source were analysed.43 patients who received Bortezomib based therapy as first line had been identified. The haematological response was assessed according to the International Society of Amyloidosis criteria. The duration to complete remission and relapse rates were also analysed.Results:55 patients were diagnosed with AL amyloidosis between 2001 and 2018. Half of the patients were referred by renal service (49%) and 11/55 (20%) were from cardiology service. Two third (38/55) of the patients had lambda light chains. Vast majority (87%) had either MGUS or smouldering myeloma.Half of the patients were diagnosed from renal biopsy. Other sites of diagnostic biopsy sample include bone marrow, lymph node, cardiac, GI tract, liver and tongue. Congo red stain was done on 39/50 bone marrow trephine samples and 16 of them (41%) were positive (8 muscular layer, 1 cortical bone, 7 marrow interstitium). Rectal biopsies were done on 10 patients with 7 positive result (70%).Of the 43 patients who received Bortezomib based therapy as first line treatment, 14 (32.6%) achieved complete response within 30 days of commencing treatment. Three patients (21.4%) relapsed with median time to relapse of 3.6 years. 15 patients (34.9%) achieved complete response after 30 days of commencing therapy and 5 patients (33.3%) relapsed with median time of 2 years. Five patients achieved very good partial response (VGPR), six patients with limited or no response.Summary/Conclusion:Renal disease is the most common presentation of AL amyloidosis followed by cardiac involvement. 2/3 of patients have elevated serum free lambda light chain and most of them have either MGUS or smouldering myeloma on bone marrow biopsy. Diagnoses are mostly made on renal biopsy but rectal biopsy seems to be sensitive for diagnosis of amyloidosis infiltration as well. Bortezomib based therapy appeared to be effective treatment as first line therapy with 79% achieving good haematological response with sustainable remission status. Ongoing follow up and larger cohort will be required for more conclusive results.