Safety and efficacy of high-dose melphalan and auto-SCT in patients with AL amyloidosis and cardiac involvement

Abstract

In Ig light chain (AL) amyloidosis, cardiac involvement is associated with worse prognosis and increased treatment-related complications. In this retrospective cohort study, we assessed survival, hematologic and cardiac responses to high-dose melphalan and auto-SCT (HDM/SCT) in patients with AL amyloidosis and cardiac involvement, stratified by cardiac biomarkers brain natriuretic peptide and Troponin I, analogous to the Mayo cardiac staging. Forty-seven patients underwent HDM/SCT based upon functional measures; six patients had modified cardiac stage I disease, seventeen had modified cardiac stage II disease and twenty-four had modified cardiac stage III disease. Treatment-related mortality was 4% for all patients and 8% for patients with stage III disease. Three-year survival was 88% and EFS was 47%; these did not differ by stage. By intention-to-treat analysis, 27% of patients achieved a hematologic complete response and 32% a very good partial response, of whom 70 and 45%, respectively, have not required additional therapy at 36 months. Cardiac response was achieved in 53% of patients. We conclude that with appropriate patient selection and a risk-adapted treatment approach, HDM/SCT is safe and effective in patients with AL amyloidosis and cardiac involvement.

High-dose therapy with auto-SCT is feasible in high-risk cardiac amyloidosis

“…As we utilize a low threshold for ICU transfers for transplant patients with cardiac arrhythmias, it may have contributed to the improved overall mortality and outcome. In the current study, HR was observed in 86% of the patients at 1-year post transplant with 23% CHR, comparable to the previous reports including Madan et al, 14 where a HR of 66% and CHR of 30% were reported in 187 cardiac amyloidosis patients, and Girnius et al, 22 where 27% CHR in 47 cardiac amyloidosis patients was reported in HDT-ASCT setting. However, as opposed to the recent data reported by the Mayo group, 23 HR before transplant (63%) or in the immediate post-transplant setting (80%) did not translate into improved OS or EFS in our study.…”

Prognostic impact of cytogenetic aberrations in AL amyloidosis patients after high-dose melphalan: a long-term follow-up study

“…We observed CR rates in the 30% to 40% range, similar to those previously reported by other groups. 2,15,16,36,37,41,42 TRM after HDM was very low with a single death. Because eligibility criteria for HDM at our institution are comparable to those of other centers, 15 our study is representative and corroborates the value of HDM as a treatment option for selected eligible patients at experienced centers, even in the era of novel agents.…”

Plerixafor and Abbreviated-Course Granulocyte Colony–Stimulating Factor for Mobilizing Hematopoietic Progenitor Cells in Light Chain Amyloidosis

“…High-dose melphalan with autologous hematopoietic cell transplantation (auto-HCT) can provide deep hematological responses, reversal of amyloid-related organ dysfunction, and sustained disease control in a subset of fitter AL amyloidosis patients [2][3][4]. Despite its promise, treatment with this modality has so far been limited by high treatment-related mortality for many patients, owing to high morbidity from amyloid organ involvement [5,6]. Recent trends have shown improved outcomes of auto-HCT in experienced transplantation centers that adhere to careful patient selection [7].…”