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.

Improved outcomes for newly diagnosed AL amyloidosis between 2000 and 2014: cracking the glass ceiling of early death

“…Another potential explanation is the inferior outcomes seen in patients with t(11;14) treated with bortezomib. 24,25 This aspect of therapy requires more study.…”

MAGE genes: Prognostic indicators in AL amyloidosis patients

“…The expression level of MAGE‐C1/CT7 correlated with the level of cTnI. Chromosomal abnormalities, including 1q21, t (11; 14), were associated with poor survival rates . In this study, patients with MAGE A3 expression had more frequent 1q21 amplification.…”

Recent Advances in the Diagnosis, Risk Stratification, and Management of Systemic Light-Chain Amyloidosis

“…The frequency of del(17p) in AL amyloidosis is 3% [43]. These MM high-risk FISH aberrations, t(4; 14), t(14; 16), and del(17p), conferred no adverse prognosis in patients treated with bortezomib [44].…”

“…These patients have a lower rate of very good partial response (VGPR) or better, and an inferior overall survival (OS) when treated with bortezomib [44]. Trisomies were associated with a shorter OS, reaching statistical significance only for patients treated with melphalan [43]. Patients with t(11; 14) should be considered for autologous stem cell transplantation (ASCT) or standard-dose melphalan at diagnosis because the survival disadvantage may be abrogated.…”

“…Often the amyloidogenic clone is characterized by chromosomal abnormalities [42]. The most frequent genetic abnormalities in AL amyloidosis are t(11; 14) (50%) [42], monosomy 13/del(13q) (36%), and trisomies (26%) [43]. …”