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Multiple myeloma gammopathies

Revisiting complete response in light chain amyloidosis

Leukemia volume 34, pages 1472–1475 (2020)Cite this article

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Organ dysfunction in light chain amyloidosis (AL) results from deposition of misfolded monoclonal free light chains (FLC). A rapid reduction in FLC levels correlates with improvement in organ function and survival, and patients not achieving at least very good partial response (VGPR) have poor outcomes [1, 2]. The current hematologic response criteria for AL amyloidosis define complete response (CR) as no evidence of monoclonal protein based on serum and urine immunofixation, as well as achieving a normal FLC ratio. VGPR is defined as achieving a difference in involved and uninvolved light chain (dFLC) of <4 mg/dL [1]. The response criteria do not take the levels of involved FLC (iFLC) into consideration. However, even low levels of amyloidogenic monoclonal FLC can result in organ dysfunction [3,4,5]. Recent data from our group shows that increased level of iFLCs at the time of normal FLC ratio or VGPR or better response are associated with inferior outcomes [6, 7]. In addition, achievement of CR requires a normal FLC ratio, which can be skewed by discordant suppression of light chain levels [8]. We sought to examine the role of iFLC levels and FLC ratio in patients who have achieved a normal serum immunofixation and do not have any evidence of monoclonal protein in urine.

Patients with AL amyloidosis diagnosed from 2006 to 2015 with the following response to first-line therapy were included: CR [CR group] or patients with VGPR who met all criteria for CR, except that they had an abnormal FLC ratio [IFE negative VGPR group]. Serum FLC levels were as categorized as high, low, or normal based on reference range of the Freelite assay (The Binding Site); lambda: 0.57–2.63 mg/dL, kappa: 0.3–1.94 mg/dL, kappa/lambda ratio 0.26–1.65 [9]. Organ involvement and responses were assessed by established criteria [1, 10, 11]. Responses were assessed as best response to first-line therapy. Progression-free survival (PFS) was defined as time from start of first-line therapy to relapse/progression requiring a change in treatment or death. Landmark survival analysis from best response was also conducted. This study was approved by the Institutional Review Board and patients provided consent for use of data for research.

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Funding

Amyloidosis Foundation.

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Authors and Affiliations

  1. Division of Blood and Marrow Transplantation, Stanford University, Stanford, CA, USA

    Surbhi Sidana

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

    Surbhi Sidana, Angela Dispenzieri, Ronald S. Go, Francis K. Buadi, Martha Q. Lacy, Wilson I. Gonsalves, David Dingli, Rahma Warsame, Taxiarchis Kourelis, Eli Muchtar, Suzanne R. Hayman, Prashant Kapoor, Robert A. Kyle, Nelson Leung, S. Vincent Rajkumar, Morie A. Gertz & Shaji K. Kumar

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

    David L. Murray

  4. Division of Nephrology, Mayo Clinic, Rochester, MN, USA

    Nelson Leung

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  1. Surbhi Sidana
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Contributions

SS and SKK designed the study, collected and analyzed the data and wrote the first draft of the paper. Remaining authors critically appraised the first and subsequent drafts of the paper.

Corresponding author

Correspondence to Shaji K. Kumar.

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Conflict of interest

SS: Honoraria (advisory board), Janssen; AD: Research Funding from Celgene, Takeda, Prothena, Jannsen, Pfizer, Alnylam, GSK; PK: Research Funding from Celgene, Takeda. MQL: Research Funding from Celgene; MAG: Honoraria/consultancy from Ionis, Alnylam, Prothena, Celgene, Janssen, Specytrum, Annexon, Apellis, Amgen, Medscape, Abbvie, Research to Practice, Physcians Education Resource and Teva; SKK: Research Funding and membership on an entity’s Board of Directors or advisory committees: AbbVie, Celgene, Janssen, KITE, Merck. Membership on an entity’s Board of Directors or advisory committees: Oncopeptides, Takeda. Research funding from Novartis and Roche. All potential conflict of interest have been disclosed.

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Sidana, S., Dispenzieri, A., Murray, D.L. et al. Revisiting complete response in light chain amyloidosis. Leukemia 34, 1472–1475 (2020). https://doi.org/10.1038/s41375-019-0664-9

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