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

[Jm954]

On line abstract report 21 May 2021

The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib has revolutionised the therapeutic landscape of chronic lymphocytic leukaemia (CLL). Acquired mutations emerging at position C481 in the BTK tyrosine kinase domain are the predominant genetic alterations associated with secondary ibrutinib resistance.

To assess the correlation between disease progression, and the emergence and temporal dynamics of the most common resistance mutation, BTKC481S , sensitive (10-4 ), time-resolved screening was performed in 83 relapsed/refractory CLL patients during single-agent ibrutinib treatment. With a median follow-up time of 40 months, BTKC481S was detected in 48·2% (40/83) of the patients, with 80·0% (32/40) of them showing disease progression during the examined period.

In these 32 cases showing disease progression, representing 72·7% (32/44) of all patients experiencing relapse, emergence of the BTKC481S mutation preceded the symptoms of clinical relapse with a median of nine months. Subsequent Bcl-2 inhibition therapy applied in 28/32 patients harbouring BTKC481S and progressing on ibrutinib conferred clinical and molecular remission across the patients.

The study demonstrates the clinical value of sensitive BTKC481S monitoring with the largest longitudinally analysed real-world patient cohort reported to date and validates the feasibility of an early prediction of relapse in the majority of ibrutinib-treated relapsed/refractory CLL patients experiencing disease progression.

Abstracthere: pubmed.ncbi.nlm.nih.gov/340...

Jackie

[pkguk2 Partner CLL Support Association]

Thanks Jackie. This is important research and thank you for highlighting it

[db601]

Thanks, Jackie. So difficult to get the follow up monitoring.

I’ve had to add MSKCC to my medical portal collection. Fortunately, Dr Anthony R Mato - really wonderful - has agreed to see me again - and work towards a drug change.

Thank you for helping us to understand the current reprints. Diana

[Jm954 Administrator in reply to db601]

You’re right, unless you’re part of a trial it’s almost impossible to get these done and even then it’s rare. I looked for places to get these tests and couldn’t positively identify any.