Light-chain cardiac amyloidosis: a case report of extraordinary sustained pathological response to cyclophosphamide, bortezomib, and dexamethasone combined therapy

Abstract

Background: Heart involvement represents the most ominous prognostic factor in light-chain amyloidosis (AL), often foreclosing curative therapies such as high-dose chemotherapy followed by autologous stem cell transplantation (ASCT). Heart transplantation (HTx) may be considered before ASCT in rigorously selected cases of advanced AL cardiac amyloidosis (CA). In ASCT-ineligible patients, chemotherapy with cyclophosphamide, bortezomib, and dexamethasone combined (CyBorD) regimen, even at low-dose, is feasible and effective in obtaining hematological and organ response.

Case summary: A previously healthy 50-year-old woman presented with severely symptomatic new-onset heart with preserved ejection fraction, significant cardiac hypertrophy, and an 'apical sparing' pattern. Bone marrow and abdominal fat biopsy revealed AL amyloidosis due to a smouldering micromolecular λ-type myeloma with severe cardiac involvement, and the patient was judged a good candidate to HTx followed by ASCT. Despite fragile conditions, she tolerated a full course of low-dose combination therapy with bortezomib and was withdrawn from HTx list because of unexpected persistent complete hematologic response and major cardiac improvement. Disease remission was achieved in the long term (>3 years).

Discussion: We report a case of exceptional persistent hematologic and cardiac response after CyBorD therapy in a patient with advanced AL-CA who left the transplantation lists (both HTx and ASCT). In ASCT-ineligible patients, chemotherapy with CyBorD regimen, even at low-dose, can lead to durable remission of the disease with excellent cardiac response.

Keywords: Autologous stem cell transplantation; Case report; CyBorD therapy; Heart failure; Heart transplantation; Light chain cardiac amyloidosis.

Figure 1

Main diagnostic tests used for diagnosing cardiac amyloidosis: electrocardiogram with normal QRS voltage and evidence of pseudonecrosis (A), echocardiography reporting biventricular hypertrophy, valvular thickening and pericardial effusion (B), grade 1 Perugini at diphosphonate scintigraphy (C) and atypical plasmacellular infiltrate with free light chains lambda restriction at bone marrow biopsy (D).

Figure 2

Echocardiographic findings pre (left column) and post (right column) chemotherapy with cyclophosphamide, bortezomib, and dexamethasone combined protocol: four-chamber view (A), mitral inflow posterior wall (B) and global longitudinal strain (C).

Figure 3

Trends of brain natriuretic peptide (pg/mL), immunoglobulin G lambda (mg/dL) and peak maximal oxygen consumption during exercise (% of predicted value) during follow up. cyclophosphamide, bortezomib, and dexamethasone combined therapy administered between February and June 2018.