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

Abstract:

: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.

journal_name

Br J Haematol

authors

Castillo JJ,Xu L,Gustine JN,Keezer A,Meid K,Dubeau TE,Liu X,Demos MG,Kofides A,Tsakmaklis N,Chen JG,Munshi M,Guerrera ML,Chan GG,Patterson CJ,Yang G,Hunter ZR,Treon SP

doi

10.1111/bjh.16088

subject

Has Abstract

pub_date

2019-11-01 00:00:00

pages

356-363

issue

3

eissn

0007-1048

issn

1365-2141

journal_volume

187

pub_type

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