Rob Dillard

DocwireNews

The prevalence of Bruton&rsquo;s tyrosine kinase (BTK) C481 mutations, a known cause of resistance to BTK inhibitors (BTKi), might be higher in chronic lymphocytic leukemia (CLL) patients with longer BTKi exposure, according to a study <a href="https://ash.confex.com/ash/2023/webprogram/Paper181105.html" target="_blank" rel="noopener">presented</a> at the 65th ASH Annual Meeting &amp; Exposition, which is taking place December 9-12 in San Diego, California.&ldquo;Almost two-thirds of [patients] whose disease progresses on a covalent BTKi have a BTK C481 mutation detectable at progression. Furthermore, BTK C481 mutations have been detected up to 28 months before progression among [patients] with CLL/[small lymphocytic lymphoma (SLL)] treated with a covalent BTKi. The early identification of patients who are at risk for developing covalent BTKi resistance is critical to optimize clinical treatment of [patients] with CLL/SLL,&rdquo; the researchers wrote.In this cross-sectional study, Jennifer Prescott and colleagues assessed the prevalence of BTK C481 mutations in 130 patients with CLL/SLL. The researchers noted that DNA was assayed from blood samples collated for 6 BTK C481 mutations known to confer resistance to covalent BTKi (c.1442G&gt;C, c.1441T&gt;A, c.1442_1443delinsCT, c.1442G&gt;T, c.1441T&gt;C, and c.1442G&gt;A). Patients were considered to have a BTK C481 mutation if any of the 6 variants showed an abnormal limit of detection.&ldquo;Because two-thirds of BTKi-experienced [patients] had &lt;36 [months] of BTKi exposure, the prevalence of BTK C481 mutations may be higher in populations with longer BTKi exposure,&rdquo; the researchers concluded. &ldquo;Further analyses of the natural history of BTK C481 mutations will help identify patients who are at risk of covalent BTKi resistance.&rdquo;ReferencePrescott J, Steiniche T, Georgsen J, et al. Prevalence of resistance-associated Bruton tyrosine kinase (BTK) C481 mutations by prior treatment status among patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL): a real-world observational study. Abstract #4196. Presented at the 65th ASH Annual Meeting &amp; Exposition; December 9-12, 2023; San Diego, California.

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BTK C481 Mutations Higher Among CLL Patients With Longer BTKi Exposure

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The prevalence of BTK C481 mutations, a known cause of resistance to BTK inhibitors, might be higher in CLL patients with longer exposure to BTKi.

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