Survival impact of achieving minimal residual negativity by multi-parametric flow cytometry in AL amyloidosis

Eli Muchtar, Angela Dispenzieri, Dragan Jevremovic, David Dingli, Francis K. Buadi, Martha Q. Lacy, Wilson Gonsalves, Rahma Warsame, Taxiarchis V. Kourelis, Suzanne R. Hayman, Prashant Kapoor, Nelson Leung, Stephen Russell, John A. Lust, Yi Lin, Ronald S. Go, Steven Zeldenrust, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. KumarMorie A. Gertz

Research output: Contribution to journalArticle

Abstract

Response assessment in light chain (AL) amyloidosis is challenging given the low level of circulating free light chains usually seen. Multi-parametric flow cytometry (MFC) from a marrow aspirate was demonstrated to retain a prognostic significance in several recent studies. In this work, 82 AL patients who had MFC study at end of therapy were analysed based on whether clonal plasma cells were detected or not. Among patients who achieved deep response (i.e. very good partial response or complete response) to first-line therapy, lack of clonal marrow plasma cells as measured by MFC was associated with improved progression-free survival (PFS) compared to patients with residual clonal plasma cells (3-year PFS 88% vs. 46%, p =.003), particularly among patients who achieved a complete response (3-year PFS 100% vs. 33%, p =.001). Absence of clonal plasma cells by MFC compared with patients with detectable clonal plasma cells among deep responders was associated with lower level of involved light chain (involved free light chain (iFLC), median 1.1 vs. 1.7 mg/dL; p =.02) and higher frequency of renal response (100% vs. 68%; p =.005). Further studies are needed to determine if MFC should be incorporated into response criteria in AL amyloidosis.

Original languageEnglish (US)
JournalAmyloid
DOIs
StateAccepted/In press - Jan 1 2019

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Amyloidosis
Plasma Cells
Flow Cytometry
Survival
Disease-Free Survival
Light
Bone Marrow
Kidney
Therapeutics

Keywords

  • Flow cytometry
  • light chain
  • minimal residual disease
  • response
  • survival

ASJC Scopus subject areas

  • Internal Medicine

Cite this

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title = "Survival impact of achieving minimal residual negativity by multi-parametric flow cytometry in AL amyloidosis",
abstract = "Response assessment in light chain (AL) amyloidosis is challenging given the low level of circulating free light chains usually seen. Multi-parametric flow cytometry (MFC) from a marrow aspirate was demonstrated to retain a prognostic significance in several recent studies. In this work, 82 AL patients who had MFC study at end of therapy were analysed based on whether clonal plasma cells were detected or not. Among patients who achieved deep response (i.e. very good partial response or complete response) to first-line therapy, lack of clonal marrow plasma cells as measured by MFC was associated with improved progression-free survival (PFS) compared to patients with residual clonal plasma cells (3-year PFS 88{\%} vs. 46{\%}, p =.003), particularly among patients who achieved a complete response (3-year PFS 100{\%} vs. 33{\%}, p =.001). Absence of clonal plasma cells by MFC compared with patients with detectable clonal plasma cells among deep responders was associated with lower level of involved light chain (involved free light chain (iFLC), median 1.1 vs. 1.7 mg/dL; p =.02) and higher frequency of renal response (100{\%} vs. 68{\%}; p =.005). Further studies are needed to determine if MFC should be incorporated into response criteria in AL amyloidosis.",
keywords = "Flow cytometry, light chain, minimal residual disease, response, survival",
author = "Eli Muchtar and Angela Dispenzieri and Dragan Jevremovic and David Dingli and Buadi, {Francis K.} and Lacy, {Martha Q.} and Wilson Gonsalves and Rahma Warsame and Kourelis, {Taxiarchis V.} and Hayman, {Suzanne R.} and Prashant Kapoor and Nelson Leung and Stephen Russell and Lust, {John A.} and Yi Lin and Go, {Ronald S.} and Steven Zeldenrust and Kyle, {Robert A.} and Rajkumar, {S. Vincent} and Kumar, {Shaji K.} and Gertz, {Morie A.}",
year = "2019",
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T1 - Survival impact of achieving minimal residual negativity by multi-parametric flow cytometry in AL amyloidosis

AU - Muchtar, Eli

AU - Dispenzieri, Angela

AU - Jevremovic, Dragan

AU - Dingli, David

AU - Buadi, Francis K.

AU - Lacy, Martha Q.

AU - Gonsalves, Wilson

AU - Warsame, Rahma

AU - Kourelis, Taxiarchis V.

AU - Hayman, Suzanne R.

AU - Kapoor, Prashant

AU - Leung, Nelson

AU - Russell, Stephen

AU - Lust, John A.

AU - Lin, Yi

AU - Go, Ronald S.

AU - Zeldenrust, Steven

AU - Kyle, Robert A.

AU - Rajkumar, S. Vincent

AU - Kumar, Shaji K.

AU - Gertz, Morie A.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Response assessment in light chain (AL) amyloidosis is challenging given the low level of circulating free light chains usually seen. Multi-parametric flow cytometry (MFC) from a marrow aspirate was demonstrated to retain a prognostic significance in several recent studies. In this work, 82 AL patients who had MFC study at end of therapy were analysed based on whether clonal plasma cells were detected or not. Among patients who achieved deep response (i.e. very good partial response or complete response) to first-line therapy, lack of clonal marrow plasma cells as measured by MFC was associated with improved progression-free survival (PFS) compared to patients with residual clonal plasma cells (3-year PFS 88% vs. 46%, p =.003), particularly among patients who achieved a complete response (3-year PFS 100% vs. 33%, p =.001). Absence of clonal plasma cells by MFC compared with patients with detectable clonal plasma cells among deep responders was associated with lower level of involved light chain (involved free light chain (iFLC), median 1.1 vs. 1.7 mg/dL; p =.02) and higher frequency of renal response (100% vs. 68%; p =.005). Further studies are needed to determine if MFC should be incorporated into response criteria in AL amyloidosis.

AB - Response assessment in light chain (AL) amyloidosis is challenging given the low level of circulating free light chains usually seen. Multi-parametric flow cytometry (MFC) from a marrow aspirate was demonstrated to retain a prognostic significance in several recent studies. In this work, 82 AL patients who had MFC study at end of therapy were analysed based on whether clonal plasma cells were detected or not. Among patients who achieved deep response (i.e. very good partial response or complete response) to first-line therapy, lack of clonal marrow plasma cells as measured by MFC was associated with improved progression-free survival (PFS) compared to patients with residual clonal plasma cells (3-year PFS 88% vs. 46%, p =.003), particularly among patients who achieved a complete response (3-year PFS 100% vs. 33%, p =.001). Absence of clonal plasma cells by MFC compared with patients with detectable clonal plasma cells among deep responders was associated with lower level of involved light chain (involved free light chain (iFLC), median 1.1 vs. 1.7 mg/dL; p =.02) and higher frequency of renal response (100% vs. 68%; p =.005). Further studies are needed to determine if MFC should be incorporated into response criteria in AL amyloidosis.

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