More than half of patients with chronic lymphocytic leukemia (CLL) who received ibrutinib for more than 3 years and had residual clonal lymphocytosis were found through next-generation sequencing to have a BTK mutation, and presence of this mutation was associated with subsequent disease progression, according to data from a FILO group study.1

analyses performed following acquired ibrutinib resistance have suggested that
CLL progression on ibrutinib is linked to mutations in the Bruton’s tyrosine
kinase (BTK) and/or phospholipase
Cg2 (PLCG2) genes,”
researchers wrote. “However, mutational information for patients still on
ibrutinib, without evidence of CLL progression, is limited.”

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in this study, researchers wanted to evaluate a group of real-life patients
being treated with ibrutinib as part of an early-access program launched in
2014 that allowed for prolonged use of the drug.

204 patients across 29 French Innovative Leukemia Organization (FILO) centers who
were enrolled in the early-access program, 31% (63 patients) were still on
ibrutinib after 3 years and were able to provide a fresh blood sample.

the 63 patients, 30 had a CLL clone of 0.5 x 109/L or greater and
were able to undergo next-generation sequencing. At least one BTK
mutation was present in 57% of samples, and PLCG2 mutations were found
in 13% of samples.

a median follow-up of 8.5 months from sample collection, those patients with a BTK
mutation has significantly higher risk for CLL progression compared with
patients who had no mutation (P =.0005).

findings support that mutational analyses should be considered in patients
receiving ibrutinib who have residual clonal lymphocytosis, and that clinical
trials are needed to evaluate whether patients with a BTK mutation may
benefit from an early switch to another treatment,” the researchers wrote.


Quinquenel A, Fornecker LM, Letestu R, et al. Prevalence of BTK and PLCG2 mutations in a real-life CLL cohort still on ibrutinib after three years: FILO group study. [published online June 26, 2019]. Blood. doi: 10.1182/blood.2019000854

This article originally appeared on Cancer Therapy Advisor