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Association details:
Evidence:
Evidence Level:
Resistant: C3 – Early Trials
Title:

Screening and monitoring of the BTK C481S mutation in a real-world cohort of patients with relapsed/refractory chronic lymphocytic leukaemia during ibrutinib therapy

Published date:
05/21/2021
Excerpt:
...83 relapsed/refractory CLL patients during single-agent ibrutinib treatment. With a median follow-up time of 40 months, BTK C481S was detected in 48·2% (40/83) of the patients, with 80·0% (32/40) of them showing disease progression...
DOI:
10.1111/bjh.17502
Evidence Level:
Resistant: C3 – Early Trials
Source:
Title:

BTK AND PLCG2 MUTATIONS IN PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA RELAPSING ON IBRUTINIB: A EUROPEAN RESEARCH INITIATIVE ON CLL (ERIC) STUDY BASED ON REAL-WORLD EVIDENCE

Published date:
06/12/2020
Excerpt:
Thirty-one of 59 (53%) R/R pts carried at least 1 hotspot BTK mutation (p.C481S/R/Y) (median VAF 23.3%, range, 1.4%>97.3%) (Table 1). Eight of 31 (26%) mutated pts carried ≥2 hotspot BTK mutations with different VAFs. Seven R/R pts harboring BTK mutation(s) also carried PLCG2 mutation(s) (Table 1)....This study reveals that ~50% of pts relapsing on ibrutinib had a BTK p.C481 mutation by NGS.
Evidence Level:
Resistant: C3 – Early Trials
New
Source:
Title:

Resistance mechanisms for the Bruton's tyrosine kinase inhibitor ibrutinib

Excerpt:
Functional analysis showed that the C481S mutation of BTK results in a protein that is only reversibly inhibited by ibrutinib….Resistance to the irreversible BTK inhibitor ibrutinib often involves mutation of a cysteine residue where ibrutinib binding occurs.
DOI:
10.1056/NEJMoa1400029
Evidence Level:
Resistant: C3 – Early Trials
New
Source:
Title:

Clonal evolution in patients with chronic lymphocytic leukaemia developing resistance to BTK inhibition

Excerpt:
...we dissect evolution of ibrutinib resistance in serial samples from five chronic lymphocytic leukaemia patients. In two patients, we detect BTK-C481S mutation or multiple PLCG2 mutations. The other three patients exhibit an expansion of clones harbouring del(8p) with additional driver mutations (EP300, MLL2 and EIF2A)...
DOI:
https://dx.doi.org/10.1038%2Fncomms11589