Venetoclax outcomes following discontinuation of pirtobrutinib in patients with R/R CLL

Research summary

Chronic lymphocytic leukaemia (CLL) along with its counterpart small lymphocytic lymphoma (SLL), hereafter referenced as CLL, is a common hematologic malignancy primarily affecting older adults. Historically, chemoimmunotherapy (CIT) has been the cornerstone of CLL treatment; however, its limited efficacy and safety concerns have led to the development of novel targeted therapies. Covalent BTKis (cBTKi) such as ibrutinib and acalabrutinib have been widely adopted, as they have demonstrated superior efficacy and improved safety profiles compared to traditional CIT. For patients with relapsed or refractory (R/R) CLL who experience disease progression on cBTKi therapy, the treatment options have evolved to include pirtobrutinib, a noncovalent BTKi (ncBTKi), or venetoclax (BCL2i)-based regimens. Initially, pirtobrutinib emerged as a promising alternative for patients with R/R CLL who have previously been treated with both cBTKi and BCL2 inhibitors based on the Phase 1/2 BRUIN study, which demonstrated promising efficacy and a favourable safety profile for pirtobrutinib in this patient population and led to accelerated approval by FDA. More recently, pirtobrutinib demonstrated superior efficacy and safety compared to rituximab plus bendamustine or rituximab plus idelalisib in patients with R/R CLL previously treated with cBTKi in the Phase 3 CLL-321 study. These results led to regulatory approval by the European Medicines Agency, the UK Medicines&Healthcare productsRegulatory Agency and U.S. Food and Drug Administration and provide a novel alternative treatment sequence of cBTKi to pirtobrutinib to venetoclax-based treatment, a sequence for which further evidence is now needed to inform clinical practice. One recent study suggested that venetoclax can still be effective after both cBTKi and ncBTKi, but the results were difficult to interpret because patients had very different treatment histories. This global multicentre retrospective study aims to address this evidence gap by evaluating the effectiveness of venetoclax-based treatments administered immediately following pirtobrutinib treatment in BCL2i-naive patients with R/R CLL previously treated with cBTKi. Data from medical records will be abstracted by approx. 12 sites in U.S. and Europe, including 3 UK hospitals. The overall target is to obtain at least 63 medical record abstractions across all sites.

Principal Investigator

Dr Toby Eyre

Contact us

Email: Latephasehaematology@ouh.nhs.uk

IRAS number

361488