Contributions
Abstract: EP998
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
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. AL amyloidosis is typically associated with a lower indolent clonal plasma cell burden within the bone marrow than multiple myeloma (MM). However, even low levels of unstable light chains secreted by these plasma cells can deposit in organs, resulting in organ dysfunction. Thus, the treatment of the disease aims to target the plasma cell clone and completely eliminate toxic light chain production. With the development of novel therapies, 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. However, there are several limitations inherent to FLC assays and immunofixation electrophoresis. Hematologic relapses still occur, and organ function may continue to deteriorate due to small residual clones. The small amounts of light chains produced by these plasma clones may not be detectable by conventional techniques. In MM, multiparameter flow cytometry (MFC) is being used to detect the presence of minimal residual disease (MRD), and the absence of detectable MRD has been associated with improved survival outcomes across different therapeutic regimens and lines of therapy. Such data are sparse in patients with AL amyloidosis. Some studies have shown that the absence of MRD detected by MFC is associated with superior outcomes in patients with AL amyloidosis, but these studies have limitations given the heterogeneity of patients tested and the lack of predefined time points for MRD assessment.
Aims
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 patients.
Methods
Clinical data from 25 consecutive newly diagnosed AL amyloidosis patients with MRD data tested 3 months after first-line therapy completion were retrospectively analyzed in a single center from 2012 to 2019. First-line therapy included 8 courses of VD or 4 courses of VD and sequential autologous stem cell transplantation (ASCT), both without maintenance therapy.
Results
Of 25 patients with very good partial response (VGPR) or better, 19 (76%) achieved MRD negativity. There were no differences in baseline characteristics 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, renal response was observed in 82% vs 50% (P=0.116), cardiac response in 93% vs 25% (P=0.019), liver response in 100% vs 50% (p=0.286), and any organ response in 94% vs 50% (P=0.023) of patients. 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) (Figure 1).
Conclusion
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.
Keyword(s): Amyloidosis, MRD
Abstract: EP998
Type: E-Poster Presentation
Session title: Myeloma and other monoclonal gammopathies - Clinical
Background
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. AL amyloidosis is typically associated with a lower indolent clonal plasma cell burden within the bone marrow than multiple myeloma (MM). However, even low levels of unstable light chains secreted by these plasma cells can deposit in organs, resulting in organ dysfunction. Thus, the treatment of the disease aims to target the plasma cell clone and completely eliminate toxic light chain production. With the development of novel therapies, 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. However, there are several limitations inherent to FLC assays and immunofixation electrophoresis. Hematologic relapses still occur, and organ function may continue to deteriorate due to small residual clones. The small amounts of light chains produced by these plasma clones may not be detectable by conventional techniques. In MM, multiparameter flow cytometry (MFC) is being used to detect the presence of minimal residual disease (MRD), and the absence of detectable MRD has been associated with improved survival outcomes across different therapeutic regimens and lines of therapy. Such data are sparse in patients with AL amyloidosis. Some studies have shown that the absence of MRD detected by MFC is associated with superior outcomes in patients with AL amyloidosis, but these studies have limitations given the heterogeneity of patients tested and the lack of predefined time points for MRD assessment.
Aims
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 patients.
Methods
Clinical data from 25 consecutive newly diagnosed AL amyloidosis patients with MRD data tested 3 months after first-line therapy completion were retrospectively analyzed in a single center from 2012 to 2019. First-line therapy included 8 courses of VD or 4 courses of VD and sequential autologous stem cell transplantation (ASCT), both without maintenance therapy.
Results
Of 25 patients with very good partial response (VGPR) or better, 19 (76%) achieved MRD negativity. There were no differences in baseline characteristics 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, renal response was observed in 82% vs 50% (P=0.116), cardiac response in 93% vs 25% (P=0.019), liver response in 100% vs 50% (p=0.286), and any organ response in 94% vs 50% (P=0.023) of patients. 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) (Figure 1).
Conclusion
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.
Keyword(s): Amyloidosis, MRD