Background: Background: BTKi (Bruton Tyrosine Kinase inhibitor) resistance is an unsolved problem in the treatment of R/R mantle cell lymphoma. Though subsequent therapy following ibrutinib resistance was tried these years, the survival of resistant patients was significantly reduced once Ibrutinib-treated patients relapse.

Methods: A total of 28 whole blood and tumor biopsies were collected from MCL patients with BTKi resistance with targeted sequencing using the GP79 panel. Based on 28 MCL patients' mutation data and clinical data, 6 hub genes were screened, by a gene panel of 69 genes and uni-variate COX prognostic analysis. Prognosis and responses to salvage therapy regimen were analyzed.

Results: Worse clinical features at baseline showed in MCL patients with BTKi . PFS2 was significantly shortened in ibrutinib-resistant patients. CAR-T therapy had the best response among salvage treatments. ATM, KRAS, CARD11, NOTCH2, PTPRD, and TP53 were screened by a gene panel of 69 genes (GP79) which might be a potential predictor for MCL patients with BTKi resistance.

No relevant conflicts of interest to declare.

Author notes

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Asterisk with author names denotes non-ASH members.

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