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- Title
CXCR4 mutation subtypes impact response and survival outcomes in patients with Waldenström macroglobulinaemia treated with ibrutinib.
- 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.
- Abstract
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 < 0·001) and worse PFS (Hazard ratio 4·02, 95% CI 1·95–8·26; P < 0·001) than patients without CXCR4 mutations. CXCR4FS was not associated with worse major response or PFS rates than patients without CXCR4 mutations. Our results suggest different response and PFS rates to ibrutinib for WM patients with CXCR4NS and CXCR4FS, and advocate in favour of CXCR4 mutational testing as well as CXCR4‐directed therapy.
- Subjects
CXCR4 receptors; PROGRESSION-free survival; ODDS ratio; MEDICAL care surveys
- Publication
British Journal of Haematology, 2019, Vol 187, Issue 3, p356
- ISSN
0007-1048
- Publication type
Article
- DOI
10.1111/bjh.16088