TY - JOUR
T1 - Impact of MYD88L265P mutation status on histological transformation of Waldenström Macroglobulinemia
AU - Zanwar, Saurabh
AU - Abeykoon, Jithma P.
AU - Durot, Eric
AU - King, Rebecca
AU - Perez Burbano, Gabriela E.
AU - Kumar, Shaji
AU - Gertz, Morie A.
AU - Quinquenel, Anne
AU - Delmer, Alain
AU - Gonsalves, Wilson
AU - Cornillet-Lefebvre, Pascale
AU - He, Rong
AU - Warsame, Rahma
AU - Buadi, Francis K.
AU - Novak, Anne J.
AU - Greipp, Patricia T.
AU - Inwards, David
AU - Habermann, Thomas M.
AU - Micallef, Ivana
AU - Go, Ronald
AU - Muchtar, Eli
AU - Kourelis, Taxiarchis
AU - Dispenzieri, Angela
AU - Lacy, Martha Q.
AU - Dingli, David
AU - Nowakowski, Grzegorz
AU - Thompson, Carrie A.
AU - Johnston, Patrick
AU - Thanarajasingam, Gita
AU - Bennani, N. Nora
AU - Witzig, Thomas E.
AU - Villasboas, Jose
AU - Leung, Nelson
AU - Lin, Yi
AU - Kyle, Robert A.
AU - Rajkumar, S. Vincent
AU - Ansell, Stephen M.
AU - Le-Rademacher, Jennifer G.
AU - Kapoor, Prashant
N1 - Funding Information:
Dr. Kumar has received research funding from Abbvie, Celgene, Janssen, Merck, Novartis, Roche, Sanofi, and Takeda, and honoraria from Skyline Diagnostics. Dr. Gertz has received honoraria from Johnson and Johnson. Dr. Dingli has received research funding from Karyopharm Therapeutics and consulting fees from Millennium and Takeda. Dr. Lacy receives research funding from Celgene. Dr. Witzig reports receiving research funding from Celgene (Institution), Novartis (Institution), Spectrum Pharmaceuticals (Institution), and Acerta Pharma (Institution). Dr. Dispenzieri has received research funding from Celgene, Millennium, Pfizer, Prothena, Janssen and Alnyalm. Dr. Yi Lin has received research funding from Janssen. Dr. Ansell has received research funding from Bristol‐Myers Squibb, Celldex, Merck, and Seattle Genetics. Dr. Prashant Kapoor is a principal investigator on studies for which Mayo Clinic has received research funding from Takeda, Amgen, GlaxoSmithKline, Janssen, Sanofi, Sorrento and Celgene and consulting fees from Celgene and Sanofi.
Publisher Copyright:
© 2019 Wiley Periodicals, Inc.
PY - 2020/3/1
Y1 - 2020/3/1
N2 - Histological transformation in Waldenström macroglobulinemia (WM) is an uncommon complication, with limited data, particularly regarding the impact of MYD88L265P mutation on transformation. We examined risk factors and outcomes associated with transformation in WM, highlighting the role of MYD88L265P mutation. Patients with WM seen at Mayo Clinic, Rochester, USA and University Hospital of Reims, France, between 01/01/1996 and December 31, 2017 were included; 50 (4.3%) of 1147 patients transformed to a high-grade lymphoma, with median time-to-transformation of 4.5 (range 0-21) years in the transformed cohort. The MYD88L265P mutation status was known in 435/1147 (38%) patients (406 with non-transformed WM and 29 patients in transformed cohort). On multivariate analysis, MYD88WT status alone was an independent predictor of transformation (odds ratio, 7[95%CI: 2.1-23]; P =.003). Additionally, the MYD88WT status was independently associated with shorter time-to-transformation (HR 7.9 [95%CI: 2.3-27; P =.001]), with a 5-year transformation rate of 16% for MYD88WT vs 2.8% with MYD88L265P mutated patients. Patients with transformation demonstrated a significant increase in risk of death compared to patients who did not transform (HR 5.075; 95%CI: 3.8-6.8; P <.001). In conclusion, the MYD88WT status is an independent predictor of transformation and associated with a shorter time-to-transformation. Additionally, transformation conferred an inferior overall survival in patients with WM.
AB - Histological transformation in Waldenström macroglobulinemia (WM) is an uncommon complication, with limited data, particularly regarding the impact of MYD88L265P mutation on transformation. We examined risk factors and outcomes associated with transformation in WM, highlighting the role of MYD88L265P mutation. Patients with WM seen at Mayo Clinic, Rochester, USA and University Hospital of Reims, France, between 01/01/1996 and December 31, 2017 were included; 50 (4.3%) of 1147 patients transformed to a high-grade lymphoma, with median time-to-transformation of 4.5 (range 0-21) years in the transformed cohort. The MYD88L265P mutation status was known in 435/1147 (38%) patients (406 with non-transformed WM and 29 patients in transformed cohort). On multivariate analysis, MYD88WT status alone was an independent predictor of transformation (odds ratio, 7[95%CI: 2.1-23]; P =.003). Additionally, the MYD88WT status was independently associated with shorter time-to-transformation (HR 7.9 [95%CI: 2.3-27; P =.001]), with a 5-year transformation rate of 16% for MYD88WT vs 2.8% with MYD88L265P mutated patients. Patients with transformation demonstrated a significant increase in risk of death compared to patients who did not transform (HR 5.075; 95%CI: 3.8-6.8; P <.001). In conclusion, the MYD88WT status is an independent predictor of transformation and associated with a shorter time-to-transformation. Additionally, transformation conferred an inferior overall survival in patients with WM.
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U2 - 10.1002/ajh.25697
DO - 10.1002/ajh.25697
M3 - Article
C2 - 31814157
AN - SCOPUS:85077874766
SN - 0361-8609
VL - 95
SP - 274
EP - 281
JO - American journal of hematology
JF - American journal of hematology
IS - 3
ER -