Clinical value of minimal residual disease assessed by multiparameter flow cytometry in amyloid light chain amyloidosis.

Xiaozhe Li,Beihui Huang,Juan Li,Meilan Chen,Junru Liu,Jingli Gu

doi:10.1007/s00432-021-03653-z

Abstract

To assess the feasibility and prognostic value of minimal residual disease (MRD) evaluated by multiparameter flow cytometry (MFC) in newly diagnosed amyloid light chain (AL) amyloidosis. Clinical data from 25 consecutive newly diagnosed AL amyloidosis patients with MRD data tested at 3 months after first-line therapy completion were retrospectively analysed in a single centre from 2012 to 2019. First-line therapy included 8 courses of VD or 4 courses of VD plus sequential autologous stem cell transplantation (ASCT), both without maintenance therapy. Of 25 patients with very good partial response (VGPR) or better, 19 (76%) achieved MRD negativity. Baseline characteristics were not different between MRD-negative and MRD-positive patients. More ASCT patients than non-ASCT patients (90.0% vs 53.3%, p = 0.043) achieved MRD negativity. In the MRD-negative and MRD-positive groups, cardiac response was observed in 93% and 25% (p = 0.019) and any organ response in 94% and 50%, respectively (p = 0.023). At a median follow-up of 25.1 months, MRD-negative patients showed significantly longer progression-free survival (PFS) from diagnosis than MRD-positive patients (24.52 vs 76.39 months, p = 0.004). MRD negativity measured by MFC at 3 months after first-line therapy completion in patients with AL amyloidosis is measurable and associated with improved organ response rates and PFS over a long follow-up.

Highlights

Amyloid light chain (AL) amyloidosis, as a clonal plasma cell disorder, is characterized by organ dysfunction secondary to deposition of misfolded monoclonal light chains and most commonly involves the heart, kidney, and liver (Merlini et al 2018)
In the minimal residual disease (MRD)-negative and MRD-positive groups, cardiac response was observed in 93% and 25% (P=0.019) and any organ response in 94% and 50%, respectively (P=0.023)
MRD negativity measured by multiparameter flow cytometry (MFC) at 3 months after first-line therapy completion in patients with AL amyloidosis is measurable and associated with improved organ response rates and progression-free survival (PFS) over a long follow-up

Summary

Introduction

Amyloid light chain (AL) amyloidosis, as a clonal plasma cell disorder, is characterized by organ dysfunction secondary to deposition of misfolded monoclonal light chains and most commonly involves the heart, kidney, and liver (Merlini et al 2018). AL amyloidosis is typically associated with a lower indolent clonal plasma cell burden within the bone marrow than multiple myeloma (MM) (Merlini and Stone 2006). With the development of novel therapies (Muchtar et al 2017a), deep responses, as assessed by serum- or urine-based methods such as immunofixation electrophoresis and free light chain (FLC) quantification, can be achieved in a significant proportion of patients with AL amyloidosis (Palladini et al 2012). The small amounts of light chains produced by these plasma clones may not be detectable by conventional techniques (Kastritis et al 2020)

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