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Multiple myeloma gammopathies

Optimizing deep response assessment for AL amyloidosis using involved free light chain level at end of therapy: failure of the serum free light chain ratio

Leukemia volume 33, pages 527–531 (2019)Cite this article

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The baseline level of involved free light chains (iFLC) is prognostic in light chain (AL) amyloidosis [1, 2]. A reduction in iFLC is associated with improved survival and organ response [1, 3, 4], making the serum free light chain (sFLC) assay the basis for the hematological response criteria [5]. Since AL amyloidosis is associated with a low burden of iFLC, different clinical outcomes can be seen at similar response depth. In patients who achieve normal sFLC ratio (sFLCR), high iFLC continues to predict a worse outcome compared to those with a normal iFLC [6]. This study explored the impact of depth of hematological response using sFLC assay parameterson organ response and survival.

The inclusion criteria were: (1) newly diagnosed AL amyloidosis within 90 days of diagnosis between 1/2002 and 8/2015; (2) achievement of very good partial response (VGPR) or complete response (CR) to first-line therapy [5]; and (3) serial sFLC studies available. The Mayo Foundation Institutional Review Board approved the study. All patients gave written informed consent to have their medical records reviewed.

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References

  1. Dispenzieri A, Lacy MQ, Katzmann JA, Rajkumar SV, Abraham RS, Hayman SR, et al. Absolute values of immunoglobulin free light chains are prognostic in patients with primary systemic amyloidosis undergoing peripheral blood stem cell transplantation. Blood. 2006;107:3378–83.

    Article  CAS  Google Scholar 

  2. Kumar S, Dispenzieri A, Katzmann JA, Larson DR, Colby CL, Lacy MQ, et al. Serum immunoglobulin free light-chain measurement in primary amyloidosis: prognostic value and correlations with clinical features. Blood. 2010;116:5126–9.

    Article  CAS  Google Scholar 

  3. Lachmann HJ, Gallimore R, Gillmore JD, Carr-Smith HD, Bradwell AR, Pepys MB, et al. Outcome in systemic AL amyloidosis in relation to changes in concentration of circulating free immunoglobulin light chains following chemotherapy. Br J Haematol. 2003;122:78–84.

    Article  CAS  Google Scholar 

  4. Sanchorawala V, Seldin DC, Magnani B, Skinner M, Wright DG. Serum free light-chain responses after high-dose intravenous melphalan and autologous stem cell transplantation for AL (primary) amyloidosis. Bone Marrow Transplant. 2005;36:597–600.

    Article  CAS  Google Scholar 

  5. Palladini G, Dispenzieri A, Gertz MA, Kumar S, Wechalekar A, Hawkins PN, et al. New criteria for response to treatment in immunoglobulin light chain amyloidosis based on free light chain measurement and cardiac biomarkers: impact on survival outcomes. J Clin Oncol. 2012;30:4541–9.

    Article  CAS  Google Scholar 

  6. Tandon N, Sidana S, Dispenzieri A, Gertz MA, Lacy MQ, Dingli D, et al. Impact of involved free light chain (FLC) levels in patients achieving normal FLC ratio after initial therapy in light chain amyloidosis (AL). Am J Hematol. 2018;93:17–22.

    Article  CAS  Google Scholar 

  7. Comenzo RL, Reece D, Palladini G, Seldin D, Sanchorawala V, Landau H, et al. Consensus guidelines for the conduct and reporting of clinical trials in systemic light-chain amyloidosis. Leukemia. 2012;26:2317–25.

    Article  CAS  Google Scholar 

  8. Muchtar E, Jevremovic D, Dispenzieri A, Dingli D, Buadi FK, Lacy MQ, et al. The prognostic value of multiparametric flow cytometry in AL amyloidosis at diagnosis and at the end of first-line treatment. Blood. 2017;129:82–87.

    Article  CAS  Google Scholar 

  9. Sidana S, Tandon N, Dispenzieri A, Gertz MA, Rajkumar SV, Kumar SK. The importance of bone marrow examination in patients with light chain amyloidosis achieving a complete response. Leukemia. 2018;32:1243–1246

    Article  Google Scholar 

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Acknowledgements

The study was supported in part by the Jabbs Foundation (Birmingham, United Kingdom), the Henry J. Predolin Foundation (USA), and National Institutes of Health National Cancer Institute grant P50 CA186781.

Author contributions:

EM designed the study, analyzed the data, wrote the first draft, and approved the final version of the manuscript; AD, NL, MQL, FKB, DD, SRH, PK, YLH, AF, MH, WG, TK, RW, SR, JAL, YL, RSG, SZ, and SVK. SKK performed patient management, revised the manuscript critically and approved the final 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

    Eli Muchtar, Angela Dispenzieri, Nelson Leung, Martha Q. Lacy, Francis K. Buadi, David Dingli, Suzanne R. Hayman, Prashant Kapoor, Yi Lisa Hwa, Amie Fonder, Miriam Hobbs, Wilson Gonsalves, Taxiarchis V. Kourelis, Rahma Warsame, Stephen J. Russell, John A. Lust, Yi Lin, Ronald S. Go, Steven R. Zeldenrust, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar & Morie A. Gertz

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

    Nelson Leung

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Corresponding author

Correspondence to Morie A. Gertz.

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Conflict of interest

AD: Research funding (Celgene, Millennium, Pfizer, and Janssen), Travel grant (Pfizer); MQL: Research funding (Celgene); DD: Research funding (Karyopharm Therapeutics, Amgen, and Millenium Pharmaceuticals); PK: Research funding (Takeda, Celgene, and Amgen); SK: Consultancy (Celgene, Millennium, Onyx, Janssen, and BMS); and research funding (Celgene, Millennium, Novartis, Onyx AbbVie, Janssen, and BMS). MAG: Consultancy (Milleniu) and honoraria (Celgene, Millenium, Onyx, Novartis, Smith Kline, Prothena, Ionis). The remaining authors declare that they have no conflict of interest.

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Muchtar, E., Dispenzieri, A., Leung, N. et al. Optimizing deep response assessment for AL amyloidosis using involved free light chain level at end of therapy: failure of the serum free light chain ratio. Leukemia 33, 527–531 (2019). https://doi.org/10.1038/s41375-018-0258-y

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