Predictors of symptomatic hyperviscosity in Waldenström macroglobulinemia

Jithma P. Abeykoon, Saurabh Zanwar, Stephen Maxted Ansell, Jeffrey Winters, Morie Gertz, Rebecca King, David Murray, Thomas Matthew Habermann, David M Dingli, Eli Muchtar, Ronald S. Go, Nelson Leung, David J. Inwards, Francis K. Buadi, Angela Dispenzieri, Martha Lacy, Yi Lin, Wilson Gonsalves, Taxiarchis Kourelis, Thomas Elmer WitzigCarrie A Thompson, S Vincent Rajkumar, Robert A. Kyle, Shaji K Kumar, Prashant Kapoor

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Abstract

Symptomatic hyperviscosity is a well-established phenomenon in Waldenström macroglobulinemia (WM). Monoclonal IgM can variably impact intrinsic serum viscosity, leading to widely disparate symptomatic thresholds for development of hyperviscosity-related symptoms. Data regarding the predictors of symptomatic hyperviscosity and outcomes related to this complication remain scarce and a recent study proposed that IgM >6000 mg/dL be considered a new criterion for initiating therapy in otherwise asymptomatic (smoldering) WM to pre-empt hyperviscosity-related injury. Herein, we attempt to identify predictors of the development of symptomatic hyperviscosity and its impact in patients with WM. Of 997 WM patients evaluated from January, 1996 through June, 2017, symptomatic hyperviscosity was observed in 130 (13%) patients. Overall survival (OS) of these 130 patients was similar to that of patients without symptomatic hyperviscosity (median: 11.5 vs 11.6 years; P = 0.63). On multivariate-analysis, only viscosity >1.8 cp (risk ratio: 4.0, P = 0.02) assessed at the time of WM diagnosis was an independent predictor for the development of subsequent symptomatic hyperviscosity. Among patients with smoldering WM and IgM >6000 mg/dL at diagnosis (n = 13) who were managed expectantly, the median time-to-initial therapy was 6.9 years and only 15% developed hyperviscosity-related symptoms subsequently. In summary, the occurrence of symptomatic hyperviscosity does not impact OS. Serum viscosity at diagnosis of WM, and not IgM concentration, represents the single most important independent predictor for development of subsequent hyperviscosity-related symptoms. Patients with smoldering WM and high serum IgM can be safely observed in the absence of any indications per the Consensus recommendations to initiate WM-directed therapy.

Original languageEnglish (US)
JournalAmerican Journal of Hematology
DOIs
StateAccepted/In press - Jan 1 2018

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Waldenstrom Macroglobulinemia
Immunoglobulin M
Viscosity
Serum
Survival
Therapeutics
Multivariate Analysis
Odds Ratio

ASJC Scopus subject areas

  • Hematology

Cite this

@article{524b6c458bf04d6ea2994526c8b12f39,
title = "Predictors of symptomatic hyperviscosity in Waldenstr{\"o}m macroglobulinemia",
abstract = "Symptomatic hyperviscosity is a well-established phenomenon in Waldenstr{\"o}m macroglobulinemia (WM). Monoclonal IgM can variably impact intrinsic serum viscosity, leading to widely disparate symptomatic thresholds for development of hyperviscosity-related symptoms. Data regarding the predictors of symptomatic hyperviscosity and outcomes related to this complication remain scarce and a recent study proposed that IgM >6000 mg/dL be considered a new criterion for initiating therapy in otherwise asymptomatic (smoldering) WM to pre-empt hyperviscosity-related injury. Herein, we attempt to identify predictors of the development of symptomatic hyperviscosity and its impact in patients with WM. Of 997 WM patients evaluated from January, 1996 through June, 2017, symptomatic hyperviscosity was observed in 130 (13{\%}) patients. Overall survival (OS) of these 130 patients was similar to that of patients without symptomatic hyperviscosity (median: 11.5 vs 11.6 years; P = 0.63). On multivariate-analysis, only viscosity >1.8 cp (risk ratio: 4.0, P = 0.02) assessed at the time of WM diagnosis was an independent predictor for the development of subsequent symptomatic hyperviscosity. Among patients with smoldering WM and IgM >6000 mg/dL at diagnosis (n = 13) who were managed expectantly, the median time-to-initial therapy was 6.9 years and only 15{\%} developed hyperviscosity-related symptoms subsequently. In summary, the occurrence of symptomatic hyperviscosity does not impact OS. Serum viscosity at diagnosis of WM, and not IgM concentration, represents the single most important independent predictor for development of subsequent hyperviscosity-related symptoms. Patients with smoldering WM and high serum IgM can be safely observed in the absence of any indications per the Consensus recommendations to initiate WM-directed therapy.",
author = "Abeykoon, {Jithma P.} and Saurabh Zanwar and Ansell, {Stephen Maxted} and Jeffrey Winters and Morie Gertz and Rebecca King and David Murray and Habermann, {Thomas Matthew} and Dingli, {David M} and Eli Muchtar and Go, {Ronald S.} and Nelson Leung and Inwards, {David J.} and Buadi, {Francis K.} and Angela Dispenzieri and Martha Lacy and Yi Lin and Wilson Gonsalves and Taxiarchis Kourelis and Witzig, {Thomas Elmer} and Thompson, {Carrie A} and Rajkumar, {S Vincent} and Kyle, {Robert A.} and Kumar, {Shaji K} and Prashant Kapoor",
year = "2018",
month = "1",
day = "1",
doi = "10.1002/ajh.25254",
language = "English (US)",
journal = "American Journal of Hematology",
issn = "0361-8609",
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TY - JOUR

T1 - Predictors of symptomatic hyperviscosity in Waldenström macroglobulinemia

AU - Abeykoon, Jithma P.

AU - Zanwar, Saurabh

AU - Ansell, Stephen Maxted

AU - Winters, Jeffrey

AU - Gertz, Morie

AU - King, Rebecca

AU - Murray, David

AU - Habermann, Thomas Matthew

AU - Dingli, David M

AU - Muchtar, Eli

AU - Go, Ronald S.

AU - Leung, Nelson

AU - Inwards, David J.

AU - Buadi, Francis K.

AU - Dispenzieri, Angela

AU - Lacy, Martha

AU - Lin, Yi

AU - Gonsalves, Wilson

AU - Kourelis, Taxiarchis

AU - Witzig, Thomas Elmer

AU - Thompson, Carrie A

AU - Rajkumar, S Vincent

AU - Kyle, Robert A.

AU - Kumar, Shaji K

AU - Kapoor, Prashant

PY - 2018/1/1

Y1 - 2018/1/1

N2 - Symptomatic hyperviscosity is a well-established phenomenon in Waldenström macroglobulinemia (WM). Monoclonal IgM can variably impact intrinsic serum viscosity, leading to widely disparate symptomatic thresholds for development of hyperviscosity-related symptoms. Data regarding the predictors of symptomatic hyperviscosity and outcomes related to this complication remain scarce and a recent study proposed that IgM >6000 mg/dL be considered a new criterion for initiating therapy in otherwise asymptomatic (smoldering) WM to pre-empt hyperviscosity-related injury. Herein, we attempt to identify predictors of the development of symptomatic hyperviscosity and its impact in patients with WM. Of 997 WM patients evaluated from January, 1996 through June, 2017, symptomatic hyperviscosity was observed in 130 (13%) patients. Overall survival (OS) of these 130 patients was similar to that of patients without symptomatic hyperviscosity (median: 11.5 vs 11.6 years; P = 0.63). On multivariate-analysis, only viscosity >1.8 cp (risk ratio: 4.0, P = 0.02) assessed at the time of WM diagnosis was an independent predictor for the development of subsequent symptomatic hyperviscosity. Among patients with smoldering WM and IgM >6000 mg/dL at diagnosis (n = 13) who were managed expectantly, the median time-to-initial therapy was 6.9 years and only 15% developed hyperviscosity-related symptoms subsequently. In summary, the occurrence of symptomatic hyperviscosity does not impact OS. Serum viscosity at diagnosis of WM, and not IgM concentration, represents the single most important independent predictor for development of subsequent hyperviscosity-related symptoms. Patients with smoldering WM and high serum IgM can be safely observed in the absence of any indications per the Consensus recommendations to initiate WM-directed therapy.

AB - Symptomatic hyperviscosity is a well-established phenomenon in Waldenström macroglobulinemia (WM). Monoclonal IgM can variably impact intrinsic serum viscosity, leading to widely disparate symptomatic thresholds for development of hyperviscosity-related symptoms. Data regarding the predictors of symptomatic hyperviscosity and outcomes related to this complication remain scarce and a recent study proposed that IgM >6000 mg/dL be considered a new criterion for initiating therapy in otherwise asymptomatic (smoldering) WM to pre-empt hyperviscosity-related injury. Herein, we attempt to identify predictors of the development of symptomatic hyperviscosity and its impact in patients with WM. Of 997 WM patients evaluated from January, 1996 through June, 2017, symptomatic hyperviscosity was observed in 130 (13%) patients. Overall survival (OS) of these 130 patients was similar to that of patients without symptomatic hyperviscosity (median: 11.5 vs 11.6 years; P = 0.63). On multivariate-analysis, only viscosity >1.8 cp (risk ratio: 4.0, P = 0.02) assessed at the time of WM diagnosis was an independent predictor for the development of subsequent symptomatic hyperviscosity. Among patients with smoldering WM and IgM >6000 mg/dL at diagnosis (n = 13) who were managed expectantly, the median time-to-initial therapy was 6.9 years and only 15% developed hyperviscosity-related symptoms subsequently. In summary, the occurrence of symptomatic hyperviscosity does not impact OS. Serum viscosity at diagnosis of WM, and not IgM concentration, represents the single most important independent predictor for development of subsequent hyperviscosity-related symptoms. Patients with smoldering WM and high serum IgM can be safely observed in the absence of any indications per the Consensus recommendations to initiate WM-directed therapy.

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