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Multiple Myeloma, Gammopathies

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

Leukemia volume 31, pages 1562–1569 (2017)Cite this article

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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.

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Acknowledgements

The study was supported by the Jabbs foundation (Birmingham, UK) and the Henry J. Predolin Foundation (USA).

Author contributions

EM designed the study, analyzed the data, wrote the first draft and approved the final version of the manuscript; AD, SKK, DD, MQL, FKB, SRH, NL, WG, RW, TVK, SR, PK, JAL, YL, RSG, SZ, SVK performed patient management, revised the manuscript critically and approved the final version of the manuscript. RPK and RC provided critical review of the manuscript and approved the last version of the manuscript; RAK performed patients’ follow-up, revised the manuscript critically and participated in final data analysis and approval of the final version of the manuscript; MAG performed patient management, designed the study, analyzed the data, wrote the first draft and approved the final version of the manuscript.

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Authors and Affiliations

  1. Division of Hematology, Mayo Clinic, Rochester, MN, USA

    E Muchtar, A Dispenzieri, S K Kumar, D Dingli, M Q Lacy, F K Buadi, S R Hayman, P Kapoor, N Leung, R Chakraborty, W Gonsalves, R Warsame, T V Kourelis, S Russell, J A Lust, Y Lin, R S Go, S Zeldenrust, R A Kyle, S V Rajkumar & M A Gertz

  2. Department of Laboratory Medicine and Pathology, Cytogenetics Laboratory, Mayo Clinic, Rochester, MN, USA

    R P Ketterling

  3. Division of Nephrology and Hypertension, Mayo Clinic, Rochester, MN, USA

    N Leung

  4. Hospitalist Services, Essentia Health St. Joseph’s Hospital, Brainerd, MN, USA

    R Chakraborty

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  1. E Muchtar
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Corresponding author

Correspondence to M A Gertz.

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Competing interests

AD received research funding from Celgene, Millennium, Pfizer and Janssen, and travel grant from Pfizer; SKK received consultancy and research funding from Celgene, consultancy and research funding from Millennium, research funding from Novartis, consultancy and research funding from Onyx, research funding from AbbVie, consultancy and research funding from Janssen, consultancy and research funding from BMS; DD received research funding from Karyopharm Therapeutics, Amgen and Millenium Pharmaceuticals; MQL received research funding from Celgene; PK received research funding from Takeda, Celgene and Amgen; MAG received honoraria from Gertz, Celgene, Onyx, Novartis, Smith Kline, Prothena, Ionis, Amgen and also received consultancy and honoraria from Millennium. The remaining authors declare no conflict of interest.

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Muchtar, E., Dispenzieri, A., Kumar, S. et al. Interphase fluorescence in situ hybridization in untreated AL amyloidosis has an independent prognostic impact by abnormality type and treatment category. Leukemia 31, 1562–1569 (2017). https://doi.org/10.1038/leu.2016.369

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