MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia

Jithma P. Abeykoon, Jonas Paludo, Rebecca King, Stephen Maxted Ansell, Morie Gertz, Betsy R. LaPlant, Alese E. Halvorson, Wilson Gonsalves, David M Dingli, Hong Fang, S Vincent Rajkumar, Martha Lacy, Rong He, Taxiarchis Kourelis, Craig B. Reeder, Anne J Novak, Ellen McPhail, David S. Viswanatha, Thomas Elmer Witzig, Ronald S. GoThomas Matthew Habermann, Francis K. Buadi, Angela Dispenzieri, Nelson Leung, Yi Lin, Carrie A Thompson, Suzanne R. Hayman, Robert A. Kyle, Shaji K Kumar, Prashant Kapoor

Research output: Contribution to journalArticle

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Abstract

Waldenström macroglobulinemia (WM) is an immunoglobulin M-associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Owing to low prevalence of the wild-type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10-fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016, to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele-specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88WT genotype, 44 had active disease. The estimated median follow-up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4-16.5) for MYD88L265P versus 13.9 years (95% CI: 6.4-29.3) for the MYD88WT (P = 0.86). The time-to-next therapy from frontline treatment and the presenting features were similar in the two patient populations. For patients with smoldering WM at diagnosis, the median time-to-progression to active disease was 2.8 years (95% CI: 2.2-3.8) in the MYD88L265P cohort and 1.9 years (95% CI: 0.7-3.1) in the MYD88WT cohort (P = 0.21). The frequency of transformation to high-grade lymphoma, or the development of therapy-elated myelodysplastic syndrome was higher in the MYD88WT cohort (16% versus 4% in the MYD88L265P, P = 0.009). In conclusion, MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease-defining feature in WM. Our findings warrant external validation, preferably through prospective studies.

Original languageEnglish (US)
Pages (from-to)187-194
Number of pages8
JournalAmerican Journal of Hematology
Volume93
Issue number2
DOIs
StatePublished - Feb 1 2018

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Waldenstrom Macroglobulinemia
Mutation
Survival
Genotype
Myelodysplastic Syndromes
Non-Hodgkin's Lymphoma
Population
Immunoglobulin M
Lymphoma
Therapeutics
Alleles
Prospective Studies
Polymerase Chain Reaction
Mortality

ASJC Scopus subject areas

  • Hematology

Cite this

MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia. / Abeykoon, Jithma P.; Paludo, Jonas; King, Rebecca; Ansell, Stephen Maxted; Gertz, Morie; LaPlant, Betsy R.; Halvorson, Alese E.; Gonsalves, Wilson; Dingli, David M; Fang, Hong; Rajkumar, S Vincent; Lacy, Martha; He, Rong; Kourelis, Taxiarchis; Reeder, Craig B.; Novak, Anne J; McPhail, Ellen; Viswanatha, David S.; Witzig, Thomas Elmer; Go, Ronald S.; Habermann, Thomas Matthew; Buadi, Francis K.; Dispenzieri, Angela; Leung, Nelson; Lin, Yi; Thompson, Carrie A; Hayman, Suzanne R.; Kyle, Robert A.; Kumar, Shaji K; Kapoor, Prashant.

In: American Journal of Hematology, Vol. 93, No. 2, 01.02.2018, p. 187-194.

Research output: Contribution to journalArticle

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abstract = "Waldenstr{\"o}m macroglobulinemia (WM) is an immunoglobulin M-associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Owing to low prevalence of the wild-type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10-fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016, to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele-specific polymerase chain reaction, was known in 219, and 174 (79{\%}) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21{\%}) patients with MYD88WT genotype, 44 had active disease. The estimated median follow-up was 7.0 years; median overall survival was 10.2 years (95{\%} CI: 8.4-16.5) for MYD88L265P versus 13.9 years (95{\%} CI: 6.4-29.3) for the MYD88WT (P = 0.86). The time-to-next therapy from frontline treatment and the presenting features were similar in the two patient populations. For patients with smoldering WM at diagnosis, the median time-to-progression to active disease was 2.8 years (95{\%} CI: 2.2-3.8) in the MYD88L265P cohort and 1.9 years (95{\%} CI: 0.7-3.1) in the MYD88WT cohort (P = 0.21). The frequency of transformation to high-grade lymphoma, or the development of therapy-elated myelodysplastic syndrome was higher in the MYD88WT cohort (16{\%} versus 4{\%} in the MYD88L265P, P = 0.009). In conclusion, MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease-defining feature in WM. Our findings warrant external validation, preferably through prospective studies.",
author = "Abeykoon, {Jithma P.} and Jonas Paludo and Rebecca King and Ansell, {Stephen Maxted} and Morie Gertz and LaPlant, {Betsy R.} and Halvorson, {Alese E.} and Wilson Gonsalves and Dingli, {David M} and Hong Fang and Rajkumar, {S Vincent} and Martha Lacy and Rong He and Taxiarchis Kourelis and Reeder, {Craig B.} and Novak, {Anne J} and Ellen McPhail and Viswanatha, {David S.} and Witzig, {Thomas Elmer} and Go, {Ronald S.} and Habermann, {Thomas Matthew} and Buadi, {Francis K.} and Angela Dispenzieri and Nelson Leung and Yi Lin and Thompson, {Carrie A} and Hayman, {Suzanne R.} and Kyle, {Robert A.} and Kumar, {Shaji K} and Prashant Kapoor",
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T1 - MYD88 mutation status does not impact overall survival in Waldenström macroglobulinemia

AU - Abeykoon, Jithma P.

AU - Paludo, Jonas

AU - King, Rebecca

AU - Ansell, Stephen Maxted

AU - Gertz, Morie

AU - LaPlant, Betsy R.

AU - Halvorson, Alese E.

AU - Gonsalves, Wilson

AU - Dingli, David M

AU - Fang, Hong

AU - Rajkumar, S Vincent

AU - Lacy, Martha

AU - He, Rong

AU - Kourelis, Taxiarchis

AU - Reeder, Craig B.

AU - Novak, Anne J

AU - McPhail, Ellen

AU - Viswanatha, David S.

AU - Witzig, Thomas Elmer

AU - Go, Ronald S.

AU - Habermann, Thomas Matthew

AU - Buadi, Francis K.

AU - Dispenzieri, Angela

AU - Leung, Nelson

AU - Lin, Yi

AU - Thompson, Carrie A

AU - Hayman, Suzanne R.

AU - Kyle, Robert A.

AU - Kumar, Shaji K

AU - Kapoor, Prashant

PY - 2018/2/1

Y1 - 2018/2/1

N2 - Waldenström macroglobulinemia (WM) is an immunoglobulin M-associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Owing to low prevalence of the wild-type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10-fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016, to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele-specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88WT genotype, 44 had active disease. The estimated median follow-up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4-16.5) for MYD88L265P versus 13.9 years (95% CI: 6.4-29.3) for the MYD88WT (P = 0.86). The time-to-next therapy from frontline treatment and the presenting features were similar in the two patient populations. For patients with smoldering WM at diagnosis, the median time-to-progression to active disease was 2.8 years (95% CI: 2.2-3.8) in the MYD88L265P cohort and 1.9 years (95% CI: 0.7-3.1) in the MYD88WT cohort (P = 0.21). The frequency of transformation to high-grade lymphoma, or the development of therapy-elated myelodysplastic syndrome was higher in the MYD88WT cohort (16% versus 4% in the MYD88L265P, P = 0.009). In conclusion, MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease-defining feature in WM. Our findings warrant external validation, preferably through prospective studies.

AB - Waldenström macroglobulinemia (WM) is an immunoglobulin M-associated lymphoma, with majority of cases demonstrating MYD88 locus alteration, most commonly, MYD88L265P. Owing to low prevalence of the wild-type (WT) MYD88 genotype in WM, clinically relevant data in this patient population are sparse, with one study showing nearly a 10-fold increased risk of mortality in this subgroup compared to patients with MYD88L265P mutation. We studied a large cohort of patients with MYD88L265P and MYD88WT WM, evaluated at Mayo Clinic, Rochester, between 1995 and 2016, to specifically assess the impact of these genotypes on clinical course. Of 557 patients, MYD88L265P mutation status, as determined by allele-specific polymerase chain reaction, was known in 219, and 174 (79%) of those exhibited MYD88L265P, 157 of 174 patients had active disease. Of 45 (21%) patients with MYD88WT genotype, 44 had active disease. The estimated median follow-up was 7.0 years; median overall survival was 10.2 years (95% CI: 8.4-16.5) for MYD88L265P versus 13.9 years (95% CI: 6.4-29.3) for the MYD88WT (P = 0.86). The time-to-next therapy from frontline treatment and the presenting features were similar in the two patient populations. For patients with smoldering WM at diagnosis, the median time-to-progression to active disease was 2.8 years (95% CI: 2.2-3.8) in the MYD88L265P cohort and 1.9 years (95% CI: 0.7-3.1) in the MYD88WT cohort (P = 0.21). The frequency of transformation to high-grade lymphoma, or the development of therapy-elated myelodysplastic syndrome was higher in the MYD88WT cohort (16% versus 4% in the MYD88L265P, P = 0.009). In conclusion, MYD88L265P mutation does not appear to be a determinant of outcome, and its presence may not be a disease-defining feature in WM. Our findings warrant external validation, preferably through prospective studies.

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