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Lymphoma

Primary systemic amyloidosis in patients with Waldenström macroglobulinemia

Leukemia volume 33, pages 790–794 (2019)Cite this article

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Waldenström macroglobulinemia (WM) is a unique IgM-associated, indolent lymphoma with at least 10% marrow lymphoplasmacytic infiltrate [1]. IgM paraprotein is implicated in 5–7% of patients with light and/or heavy chain immunoglobulin amyloidosis (AL/AHL) [2,3,4]. However, data regarding AL/AHL in WM are sparse. A greater clonal bone marrow plasma cell (BMPC) burden confers poorer survival in AL, as observed in a study from our institution (median 16 months for patients with >10% BMPCs versus 46 months), underscoring the importance of the degree of marrow infiltration at diagnosis [5]. Through this study, we attempted to address the impact of AL/AHL on the clinical course of WM and vice versa.

Following Institutional Review Board approval, records of WM patients seen at Mayo Clinic, Rochester between January 1, 1996 and June 30, 2017 were reviewed. We excluded all patients with WHO-defined IgM monoclonal gammopathy of undetermined significance (MGUS) [<10% marrow (lympho)plasmacytosis] [6]. A more recent (January 2006–December 2015) cohort of AL patients without WM (non-IgM AL), but with ≥10% BMPCs evaluated within 90 days of diagnosis of AL was selected for comparison with a contemporaneous cohort of WM patients with concurrent AL/AHL. Hematologic response and organ response to frontline therapy for AL/AHL were assessed by Consensus criteria [7]. Nonevaluable patients [difference in free light chain (dFLC) < 5 mg/dL] at therapy initiation were analyzed separately. Overall survival (OS) for WM was calculated from the diagnosis of WM until death or last follow-up. Amyloidosis-specific survival was calculated from the diagnosis of AL/AHL until death due to AL/AHL or last follow-up. All time-to-event endpoints were analyzed using the Kaplan–Meier method and compared by log-rank tests.

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Acknowledgments

The contribution of S.S. and M.A.G. to this study was supported, in part, by the grants from the International Waldenström Macroglobulinemia Foundation and the Amyloidosis Foundation.

Author contributions

S.Z., J.P.A. and P.K. designed the study. S.Z., J.P.A. and P.K. collected analyzed and interpreted the data and wrote the first draft of the manuscript. S.M.A., A.D., M.A.G., E.M., S.S., N.T., S.V.R., D.D., R.G., M.Q.L., T.K., T.E.W., D.I., F.B., W.G., T.H., P.J., G.N., R.A. and S.K. interpreted the data, critically revised the manuscript and all authors approved the final version.

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Authors and Affiliations

  1. Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA

    Saurabh Zanwar, Jithma P. Abeykoon, Stephen M. Ansell, Morie A. Gertz, Angela Dispenzieri, Eli Muchtar, Surbhi Sidana, Nidhi Tandon, S. Vincent Rajkumar, David Dingli, Ronald Go, Martha Q. Lacy, Taxiarchis Kourelis, Thomas E. Witzig, David Inwards, Francis Buadi, Wilson Gonsalves, Thomas Habermann, Patrick Johnston, Grzegorz Nowakowski, Robert A. Kyle, Shaji Kumar & Prashant Kapoor

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  1. Saurabh Zanwar
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Corresponding author

Correspondence to Prashant Kapoor.

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Conflict of interest

Dr. Ansell has received research funding from Bristol-Myers Squibb, Celldex, Merck, and Seattle Genetics. Dr. Dispenzieri has received research funding from Prothena, Jannsen, Pfizer, GSK, Takeda, Alnylam, Celgene, and serves on the advisory board for Takeda and Intellia. Dr. Gertz has received funding from Amgen, Prothena, Annexon, Appellis, Johnson and Johnson, and Celgene. Dr. Kumar has received research grants for clinical trials from Celgene, Takeda, Janssen, BMS, Sanofi, KITE, Merck, Abbvie, Medimmune, Novartis, Roche-Genentech, Amgen. Dr. Leung serves on the advisory board for Takeda and Prothena. Dr. Kapoor is principal investigator on studies for which Mayo Clinic receives funding from Takeda, Sanofi, and Amgen. The remaining authors declare that they have no conflicts of interest.

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Zanwar, S., Abeykoon, J.P., Ansell, S.M. et al. Primary systemic amyloidosis in patients with Waldenström macroglobulinemia. Leukemia 33, 790–794 (2019). https://doi.org/10.1038/s41375-018-0286-7

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