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

• Published in: Leukemia Vol. 31; no. 7; pp. 1562 - 1569
• Main Authors: Muchtar, E, Dispenzieri, A, Kumar, S K, Ketterling, R P, Dingli, D, Lacy, M Q, Buadi, F K, Hayman, S R, Kapoor, P, Leung, N, Chakraborty, R, Gonsalves, W, Warsame, R, Kourelis, T V, Russell, S, Lust, J A, Lin, Y, Go, R S, Zeldenrust, S, Kyle, R A, Rajkumar, S V, Gertz, M A
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01-07-2017; Nature Publishing Group
• Subjects: 631/208/1405; 631/443/319/1642; 692/700/1750; 692/700/565/1436; Aged; Amyloidosis; Amyloidosis - genetics; Amyloidosis - mortality; Amyloidosis - therapy; Analysis; Bortezomib; Cancer Research; Care and treatment; Chromosome abnormalities; Chromosomes, Human, Pair 11; Chromosomes, Human, Pair 14; Complications and side effects; Critical Care Medicine; Diagnosis; Drug therapy; Female; Fluorescence; Fluorescence in situ hybridization; Genetic aspects; Health aspects; Hematology; Humans; Hybridization; Immunoglobulins; In Situ Hybridization, Fluorescence - methods; Intensive; Internal Medicine; Interphase; Male; Median (statistics); Medicine; Medicine & Public Health; Melphalan; Middle Aged; Monosomy; Multivariate analysis; Oncology; original-article; Patients; Prognosis; Stem cell transplantation; Stem cells; Survival; Translocation, Genetic; Trisomy; United States
• ISSN: 0887-6924; 1476-5551
• DOI: 10.1038/leu.2016.369

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.