CXCR4 mutation subtypes impact response and survival outcomes in patients with Waldenström macroglobulinaemia treated with ibrutinib

Summary Ibrutinib is associated with response rate of 90% and median progression‐free survival (PFS) in excess of 5 years in Waldenström macroglobulinaemia (WM) patients. CXCR4 mutations are detected in 30–40% of patients with WM and associate with lower rates of response and shorter PFS to ibrutini...

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Published in:British journal of haematology 2019-11, Vol.187 (3), p.356-363
Main Authors: Castillo, Jorge J., Xu, Lian, Gustine, Joshua N., Keezer, Andrew, Meid, Kirsten, Dubeau, Toni E., Liu, Xia, Demos, Maria G., Kofides, Amanda, Tsakmaklis, Nicholas, Chen, Jiaji G., Munshi, Manit, Guerrera, Maria L., Chan, Gloria G., Patterson, Christopher J., Yang, Guang, Hunter, Zachary R., Treon, Steven P.
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
CXCR4
CXCR4 protein
Disease-Free Survival
Female
Hematology
Humans
ibrutinib
Impact response
Male
Middle Aged
Mutation
Neoplasm Proteins - genetics
Pyrazoles - administration & dosage
Pyrimidines - administration & dosage
Receptors, CXCR4 - genetics
response
Survival
Survival Rate
Waldenstrom Macroglobulinemia - drug therapy
Waldenstrom Macroglobulinemia - genetics
Waldenstrom Macroglobulinemia - mortality
Waldenström macroglobulinaemia
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Summary:Summary Ibrutinib is associated with response rate of 90% and median progression‐free survival (PFS) in excess of 5 years in Waldenström macroglobulinaemia (WM) patients. CXCR4 mutations are detected in 30–40% of patients with WM and associate with lower rates of response and shorter PFS to ibrutinib therapy. Both frameshift (CXCR4FS) and nonsense (CXCR4NS) CXCR4 mutations have been described. The impact of these mutations on outcomes to ibrutinib have not been evaluated in WM patients. We studied consecutive patients with a diagnosis of WM, on ibrutinib therapy, for the presence of CXCR4FS and CXCR4NS mutations and evaluated the differences in response and PFS between groups. Of 180 patients, 68 patients (38%) had CXCR4 mutations; 49 (27%) had CXCR4NS and 19 (11%) had CXCR4FS mutations. In multivariate models, patients with CXCR4NS had lower odds of major response (Odds ratio 0·25, 95% confidence interval [CI] 0·12–0·53; P 
ISSN:0007-1048
1365-2141
DOI:10.1111/bjh.16088