BTK mutational analysis of DLBCL patients treated with BTKi

• Research type

  Research Study

• Full title

  BTK mutational analysis of DLBCL patients treated with BTKi previously enrolled in the ACCEPT trial.

• IRAS ID

  339977

• Contact name

  Harriet S Walter

• Contact email

  hw191@le.ac.uk

• Sponsor organisation

  University of Leicester

• Duration of Study in the UK

  0 years, 11 months, 30 days

• Research summary

  Targeting B-cell receptor signalling using Bruton tyrosine kinase (BTK) inhibitors (BTKis) is a highly successful treatment modality for multiple B-cell malignancies. A number of different BTKi, including both covalent and non-covalent inhibitors are now available for use in the clinic. Unfortunately, for the majority of patients, this will not provide a curative approach and eventually resistance to treatment arises. Resistance mechanisms to BTKi vary according to both the type of BTKi received and tumour type. Early identification of relapse is important not only in terms of consideration to further lines of treatment and facilitating access to these but may also result in cost savings to the NHS.
  With the advent of high throughput molecular technologies and ability to monitor for specific BTK mutations that can arise in patients receiving a BTKi, we propose an overarching proof of principle study using both circulating tumour cells (CTCs), where present, and circulating tumour DNA (ctDNA) for minimal residual disease (MRD) assessment and detection of early relapse. Presence of ctDNA or CTC will be assessed using shallow whole genome sequencing (sWGS) to identify copy number variations suggestive of the presence of tumour cells and ddPCR assays will be used to detect the most commonly observed drug-induced BTK mutations. We will explore the prognostic and predictive value of this approach as a mean for early detection of relapse, comparing this to current standards used for disease monitoring, such as peripheral blood and bone marrow flow, and imaging.
  

• REC name

  London - Surrey Borders Research Ethics Committee

• REC reference

  24/PR/1109

• Date of REC Opinion

  13 Sep 2024

• REC opinion

  Favourable Opinion