Outcome of Patients With Newly Diagnosed Systemic Light-Chain Amyloidosis Associated With Deletion of 17p

Sandy W. Wong, Ute Hegenbart, Giovanni Palladini, Gunjan L. Shah, Heather J. Landau, Melissa Warner, Denis Toskic, Arnaud Jaccard, Timon Hansen, Joan Bladé, M. Teresa Cibeira, Efstathios Kastritis, Angela Dispenzieri, Ashutosh Wechalekar, Cindy Varga, Stefan O. Schönland, Raymond L. Comenzo

Research output: Contribution to journalArticle

Abstract

We analyzed 44 patients with newly diagnosed systemic light-chain amyloidosis (AL) and del 17p, a rare finding in AL. Predictors of overall and progression-free survival were cardiac involvement at diagnosis and hematologic response to therapy, respectively. Median survivals of patients with > 50% and ≤ 50% del 17p plasma cells were 28 and 52 months (P =.08). Introduction: Deletion 17p (del 17p) portends a poor prognosis in myeloma, but its significance in light-chain amyloidosis is unknown. Patients and Methods: We identified patients with light-chain amyloidosis and del 17p at diagnosis, and analyzed presenting characteristics, treatments, and clinical outcomes. All had baseline biopsy results showing amyloid and serologic and marrow studies, including standard fluorescence in-situ hybridization determinations of del 17p using commercial probes. Consensus criteria for hematologic and organ involvement, progression, and response were used. Kaplan-Meier (log rank) analyses and Cox regression analysis of baseline variables were used to identify predictors of overall and progression-free survival (PFS). Six-month landmark analyses were performed to assess the impact of treatment-related variables. Results: We identified 44 patients from 7 countries with median marrow and del 17p plasma cells of 22% (range, 3%-100%) and 30% (2%-93%). Ninety-five percent had cardiac involvement, including 44% stage III. Two-thirds of the patients initially received bortezomib-based therapy. Forty-nine percent of patients experienced complete response or very good partial response, with median time to best response of 4 months (range, 1-28 months). Median overall survival and PFS were 49 and 32 months. Cardiac stage and hematologic response were the key predictors of outcomes. Patients with > 50% and ≤ 50% del 17p in clonal plasma cells had median survivals of 28 and 52 months, respectively (P =.08). In landmark analyses, only hematologic response predicted both overall survival and PFS. Conclusion: Cardiac stage, hematologic response, and del 17p percentage impact outcomes in these cases. Emphasis should be placed on optimizing supportive care and achieving a deep hematologic response.

Original languageEnglish
JournalClinical Lymphoma, Myeloma and Leukemia
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Amyloidosis
Light
Disease-Free Survival
Plasma Cells
Survival
Bone Marrow
Fluorescence In Situ Hybridization
Amyloid
Therapeutics
Regression Analysis
Biopsy

Keywords

  • AL amyloidosis
  • Deletion 17p
  • FISH cytogenetics
  • Plasma cells
  • Prognosis

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

Outcome of Patients With Newly Diagnosed Systemic Light-Chain Amyloidosis Associated With Deletion of 17p. / Wong, Sandy W.; Hegenbart, Ute; Palladini, Giovanni; Shah, Gunjan L.; Landau, Heather J.; Warner, Melissa; Toskic, Denis; Jaccard, Arnaud; Hansen, Timon; Bladé, Joan; Cibeira, M. Teresa; Kastritis, Efstathios; Dispenzieri, Angela; Wechalekar, Ashutosh; Varga, Cindy; Schönland, Stefan O.; Comenzo, Raymond L.

In: Clinical Lymphoma, Myeloma and Leukemia, 01.01.2018.

Research output: Contribution to journalArticle

Wong, SW, Hegenbart, U, Palladini, G, Shah, GL, Landau, HJ, Warner, M, Toskic, D, Jaccard, A, Hansen, T, Bladé, J, Cibeira, MT, Kastritis, E, Dispenzieri, A, Wechalekar, A, Varga, C, Schönland, SO & Comenzo, RL 2018, 'Outcome of Patients With Newly Diagnosed Systemic Light-Chain Amyloidosis Associated With Deletion of 17p', Clinical Lymphoma, Myeloma and Leukemia. https://doi.org/10.1016/j.clml.2018.07.292
Wong, Sandy W. ; Hegenbart, Ute ; Palladini, Giovanni ; Shah, Gunjan L. ; Landau, Heather J. ; Warner, Melissa ; Toskic, Denis ; Jaccard, Arnaud ; Hansen, Timon ; Bladé, Joan ; Cibeira, M. Teresa ; Kastritis, Efstathios ; Dispenzieri, Angela ; Wechalekar, Ashutosh ; Varga, Cindy ; Schönland, Stefan O. ; Comenzo, Raymond L. / Outcome of Patients With Newly Diagnosed Systemic Light-Chain Amyloidosis Associated With Deletion of 17p. In: Clinical Lymphoma, Myeloma and Leukemia. 2018.
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abstract = "We analyzed 44 patients with newly diagnosed systemic light-chain amyloidosis (AL) and del 17p, a rare finding in AL. Predictors of overall and progression-free survival were cardiac involvement at diagnosis and hematologic response to therapy, respectively. Median survivals of patients with > 50{\%} and ≤ 50{\%} del 17p plasma cells were 28 and 52 months (P =.08). Introduction: Deletion 17p (del 17p) portends a poor prognosis in myeloma, but its significance in light-chain amyloidosis is unknown. Patients and Methods: We identified patients with light-chain amyloidosis and del 17p at diagnosis, and analyzed presenting characteristics, treatments, and clinical outcomes. All had baseline biopsy results showing amyloid and serologic and marrow studies, including standard fluorescence in-situ hybridization determinations of del 17p using commercial probes. Consensus criteria for hematologic and organ involvement, progression, and response were used. Kaplan-Meier (log rank) analyses and Cox regression analysis of baseline variables were used to identify predictors of overall and progression-free survival (PFS). Six-month landmark analyses were performed to assess the impact of treatment-related variables. Results: We identified 44 patients from 7 countries with median marrow and del 17p plasma cells of 22{\%} (range, 3{\%}-100{\%}) and 30{\%} (2{\%}-93{\%}). Ninety-five percent had cardiac involvement, including 44{\%} stage III. Two-thirds of the patients initially received bortezomib-based therapy. Forty-nine percent of patients experienced complete response or very good partial response, with median time to best response of 4 months (range, 1-28 months). Median overall survival and PFS were 49 and 32 months. Cardiac stage and hematologic response were the key predictors of outcomes. Patients with > 50{\%} and ≤ 50{\%} del 17p in clonal plasma cells had median survivals of 28 and 52 months, respectively (P =.08). In landmark analyses, only hematologic response predicted both overall survival and PFS. Conclusion: Cardiac stage, hematologic response, and del 17p percentage impact outcomes in these cases. Emphasis should be placed on optimizing supportive care and achieving a deep hematologic response.",
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T1 - Outcome of Patients With Newly Diagnosed Systemic Light-Chain Amyloidosis Associated With Deletion of 17p

AU - Wong, Sandy W.

AU - Hegenbart, Ute

AU - Palladini, Giovanni

AU - Shah, Gunjan L.

AU - Landau, Heather J.

AU - Warner, Melissa

AU - Toskic, Denis

AU - Jaccard, Arnaud

AU - Hansen, Timon

AU - Bladé, Joan

AU - Cibeira, M. Teresa

AU - Kastritis, Efstathios

AU - Dispenzieri, Angela

AU - Wechalekar, Ashutosh

AU - Varga, Cindy

AU - Schönland, Stefan O.

AU - Comenzo, Raymond L.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - We analyzed 44 patients with newly diagnosed systemic light-chain amyloidosis (AL) and del 17p, a rare finding in AL. Predictors of overall and progression-free survival were cardiac involvement at diagnosis and hematologic response to therapy, respectively. Median survivals of patients with > 50% and ≤ 50% del 17p plasma cells were 28 and 52 months (P =.08). Introduction: Deletion 17p (del 17p) portends a poor prognosis in myeloma, but its significance in light-chain amyloidosis is unknown. Patients and Methods: We identified patients with light-chain amyloidosis and del 17p at diagnosis, and analyzed presenting characteristics, treatments, and clinical outcomes. All had baseline biopsy results showing amyloid and serologic and marrow studies, including standard fluorescence in-situ hybridization determinations of del 17p using commercial probes. Consensus criteria for hematologic and organ involvement, progression, and response were used. Kaplan-Meier (log rank) analyses and Cox regression analysis of baseline variables were used to identify predictors of overall and progression-free survival (PFS). Six-month landmark analyses were performed to assess the impact of treatment-related variables. Results: We identified 44 patients from 7 countries with median marrow and del 17p plasma cells of 22% (range, 3%-100%) and 30% (2%-93%). Ninety-five percent had cardiac involvement, including 44% stage III. Two-thirds of the patients initially received bortezomib-based therapy. Forty-nine percent of patients experienced complete response or very good partial response, with median time to best response of 4 months (range, 1-28 months). Median overall survival and PFS were 49 and 32 months. Cardiac stage and hematologic response were the key predictors of outcomes. Patients with > 50% and ≤ 50% del 17p in clonal plasma cells had median survivals of 28 and 52 months, respectively (P =.08). In landmark analyses, only hematologic response predicted both overall survival and PFS. Conclusion: Cardiac stage, hematologic response, and del 17p percentage impact outcomes in these cases. Emphasis should be placed on optimizing supportive care and achieving a deep hematologic response.

AB - We analyzed 44 patients with newly diagnosed systemic light-chain amyloidosis (AL) and del 17p, a rare finding in AL. Predictors of overall and progression-free survival were cardiac involvement at diagnosis and hematologic response to therapy, respectively. Median survivals of patients with > 50% and ≤ 50% del 17p plasma cells were 28 and 52 months (P =.08). Introduction: Deletion 17p (del 17p) portends a poor prognosis in myeloma, but its significance in light-chain amyloidosis is unknown. Patients and Methods: We identified patients with light-chain amyloidosis and del 17p at diagnosis, and analyzed presenting characteristics, treatments, and clinical outcomes. All had baseline biopsy results showing amyloid and serologic and marrow studies, including standard fluorescence in-situ hybridization determinations of del 17p using commercial probes. Consensus criteria for hematologic and organ involvement, progression, and response were used. Kaplan-Meier (log rank) analyses and Cox regression analysis of baseline variables were used to identify predictors of overall and progression-free survival (PFS). Six-month landmark analyses were performed to assess the impact of treatment-related variables. Results: We identified 44 patients from 7 countries with median marrow and del 17p plasma cells of 22% (range, 3%-100%) and 30% (2%-93%). Ninety-five percent had cardiac involvement, including 44% stage III. Two-thirds of the patients initially received bortezomib-based therapy. Forty-nine percent of patients experienced complete response or very good partial response, with median time to best response of 4 months (range, 1-28 months). Median overall survival and PFS were 49 and 32 months. Cardiac stage and hematologic response were the key predictors of outcomes. Patients with > 50% and ≤ 50% del 17p in clonal plasma cells had median survivals of 28 and 52 months, respectively (P =.08). In landmark analyses, only hematologic response predicted both overall survival and PFS. Conclusion: Cardiac stage, hematologic response, and del 17p percentage impact outcomes in these cases. Emphasis should be placed on optimizing supportive care and achieving a deep hematologic response.

KW - AL amyloidosis

KW - Deletion 17p

KW - FISH cytogenetics

KW - Plasma cells

KW - Prognosis

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