Interphase fluorescence in situ hybridization in untreated AL amyloidosis has an independent prognostic impact by abnormality type and treatment category

E. Muchtar, Angela Dispenzieri, Shaji K Kumar, R. P. Ketterling, David M Dingli, Martha Lacy, F. K. Buadi, S. R. Hayman, Prashant Kapoor, N. Leung, R. Chakraborty, Wilson Gonsalves, R. Warsame, Taxiarchis Kourelis, Stephen J Russell, J. A. Lust, Yi Lin, R. S. Go, S. Zeldenrust, R. A. KyleS Vincent Rajkumar, Morie Gertz

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Abstract

The significance of interphase fluorescence in situ hybridization (iFISH) by regimen type was assessed in 692 immunoglobulin light-chain (AL) amyloidosis patients with iFISH at diagnosis. First-line treatment was categorized as stem cell transplant and three non-transplant regimens. The most common abnormality was t(11;14) (49% of patients) followed by monosomy 13/del(13q) (36%) and trisomies (26%). A lower rate of very good partial response (VGPR) or better was observed in patients with t(11;14) treated with bortezomib-based (52% vs 77%; P=0.004) and IMiD-based regimens (13% vs 54%; P=0.04) compared with those lacking t(11;14). This corresponded to an inferior overall survival (OS) in t(11;14)-positive bortezomib-treated (median 15 vs 27 months; P=0.05) and IMiD-treated patients (median 12 vs 32 months; P=0.05). The inferior OS associated with t(11;14) bortezomib-treated patients was restricted to patients with favorable disease. Trisomies were associated with a shorter OS (median 29 vs 69 months; P=0.001), reaching statistical significance only for melphalan (median 15 vs 32 months; P=0.02). Multivariate analysis confirmed an independent survival impact for trisomies in the entire cohort and for t(11;14) among bortezomib-treated patients. iFISH is prognostic in untreated AL amyloidosis and may influence treatment selection. Patients with t(11;14) should be considered for ASCT or standard-dose melphalan at diagnosis because the survival disadvantage may be abrogated.Leukemia advance online publication, advance online publication, 16 December 2016; doi:10.1038/leu.2016.369.

Original languageEnglish (US)
JournalLeukemia
DOIs
StateAccepted/In press - Dec 16 2016

Fingerprint

Interphase
Amyloidosis
Fluorescence In Situ Hybridization
Survival
Melphalan
Trisomy
Therapeutics
Publications
Immunoglobulin Light Chains
Monosomy
Leukemia
Stem Cells
Multivariate Analysis
Transplants
Bortezomib

ASJC Scopus subject areas

  • Hematology
  • Cancer Research
  • Anesthesiology and Pain Medicine

Cite this

@article{c55be58d363b477a95402643933a3673,
title = "Interphase fluorescence in situ hybridization in untreated AL amyloidosis has an independent prognostic impact by abnormality type and treatment category",
abstract = "The significance of interphase fluorescence in situ hybridization (iFISH) by regimen type was assessed in 692 immunoglobulin light-chain (AL) amyloidosis patients with iFISH at diagnosis. First-line treatment was categorized as stem cell transplant and three non-transplant regimens. The most common abnormality was t(11;14) (49{\%} of patients) followed by monosomy 13/del(13q) (36{\%}) and trisomies (26{\%}). A lower rate of very good partial response (VGPR) or better was observed in patients with t(11;14) treated with bortezomib-based (52{\%} vs 77{\%}; P=0.004) and IMiD-based regimens (13{\%} vs 54{\%}; P=0.04) compared with those lacking t(11;14). This corresponded to an inferior overall survival (OS) in t(11;14)-positive bortezomib-treated (median 15 vs 27 months; P=0.05) and IMiD-treated patients (median 12 vs 32 months; P=0.05). The inferior OS associated with t(11;14) bortezomib-treated patients was restricted to patients with favorable disease. Trisomies were associated with a shorter OS (median 29 vs 69 months; P=0.001), reaching statistical significance only for melphalan (median 15 vs 32 months; P=0.02). Multivariate analysis confirmed an independent survival impact for trisomies in the entire cohort and for t(11;14) among bortezomib-treated patients. iFISH is prognostic in untreated AL amyloidosis and may influence treatment selection. Patients with t(11;14) should be considered for ASCT or standard-dose melphalan at diagnosis because the survival disadvantage may be abrogated.Leukemia advance online publication, advance online publication, 16 December 2016; doi:10.1038/leu.2016.369.",
author = "E. Muchtar and Angela Dispenzieri and Kumar, {Shaji K} and Ketterling, {R. P.} and Dingli, {David M} and Martha Lacy and Buadi, {F. K.} and Hayman, {S. R.} and Prashant Kapoor and N. Leung and R. Chakraborty and Wilson Gonsalves and R. Warsame and Taxiarchis Kourelis and Russell, {Stephen J} and Lust, {J. A.} and Yi Lin and Go, {R. S.} and S. Zeldenrust and Kyle, {R. A.} and Rajkumar, {S Vincent} and Morie Gertz",
year = "2016",
month = "12",
day = "16",
doi = "10.1038/leu.2016.369",
language = "English (US)",
journal = "Leukemia",
issn = "0887-6924",
publisher = "Nature Publishing Group",

}

TY - JOUR

T1 - Interphase fluorescence in situ hybridization in untreated AL amyloidosis has an independent prognostic impact by abnormality type and treatment category

AU - Muchtar, E.

AU - Dispenzieri, Angela

AU - Kumar, Shaji K

AU - Ketterling, R. P.

AU - Dingli, David M

AU - Lacy, Martha

AU - Buadi, F. K.

AU - Hayman, S. R.

AU - Kapoor, Prashant

AU - Leung, N.

AU - Chakraborty, R.

AU - Gonsalves, Wilson

AU - Warsame, R.

AU - Kourelis, Taxiarchis

AU - Russell, Stephen J

AU - Lust, J. A.

AU - Lin, Yi

AU - Go, R. S.

AU - Zeldenrust, S.

AU - Kyle, R. A.

AU - Rajkumar, S Vincent

AU - Gertz, Morie

PY - 2016/12/16

Y1 - 2016/12/16

N2 - The significance of interphase fluorescence in situ hybridization (iFISH) by regimen type was assessed in 692 immunoglobulin light-chain (AL) amyloidosis patients with iFISH at diagnosis. First-line treatment was categorized as stem cell transplant and three non-transplant regimens. The most common abnormality was t(11;14) (49% of patients) followed by monosomy 13/del(13q) (36%) and trisomies (26%). A lower rate of very good partial response (VGPR) or better was observed in patients with t(11;14) treated with bortezomib-based (52% vs 77%; P=0.004) and IMiD-based regimens (13% vs 54%; P=0.04) compared with those lacking t(11;14). This corresponded to an inferior overall survival (OS) in t(11;14)-positive bortezomib-treated (median 15 vs 27 months; P=0.05) and IMiD-treated patients (median 12 vs 32 months; P=0.05). The inferior OS associated with t(11;14) bortezomib-treated patients was restricted to patients with favorable disease. Trisomies were associated with a shorter OS (median 29 vs 69 months; P=0.001), reaching statistical significance only for melphalan (median 15 vs 32 months; P=0.02). Multivariate analysis confirmed an independent survival impact for trisomies in the entire cohort and for t(11;14) among bortezomib-treated patients. iFISH is prognostic in untreated AL amyloidosis and may influence treatment selection. Patients with t(11;14) should be considered for ASCT or standard-dose melphalan at diagnosis because the survival disadvantage may be abrogated.Leukemia advance online publication, advance online publication, 16 December 2016; doi:10.1038/leu.2016.369.

AB - The significance of interphase fluorescence in situ hybridization (iFISH) by regimen type was assessed in 692 immunoglobulin light-chain (AL) amyloidosis patients with iFISH at diagnosis. First-line treatment was categorized as stem cell transplant and three non-transplant regimens. The most common abnormality was t(11;14) (49% of patients) followed by monosomy 13/del(13q) (36%) and trisomies (26%). A lower rate of very good partial response (VGPR) or better was observed in patients with t(11;14) treated with bortezomib-based (52% vs 77%; P=0.004) and IMiD-based regimens (13% vs 54%; P=0.04) compared with those lacking t(11;14). This corresponded to an inferior overall survival (OS) in t(11;14)-positive bortezomib-treated (median 15 vs 27 months; P=0.05) and IMiD-treated patients (median 12 vs 32 months; P=0.05). The inferior OS associated with t(11;14) bortezomib-treated patients was restricted to patients with favorable disease. Trisomies were associated with a shorter OS (median 29 vs 69 months; P=0.001), reaching statistical significance only for melphalan (median 15 vs 32 months; P=0.02). Multivariate analysis confirmed an independent survival impact for trisomies in the entire cohort and for t(11;14) among bortezomib-treated patients. iFISH is prognostic in untreated AL amyloidosis and may influence treatment selection. Patients with t(11;14) should be considered for ASCT or standard-dose melphalan at diagnosis because the survival disadvantage may be abrogated.Leukemia advance online publication, advance online publication, 16 December 2016; doi:10.1038/leu.2016.369.

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