DATA from a randomised controlled trial reveal that the duration of progression-free survival (PFS) in patients with either relapsed or refractory chronic lymphocytic leukaemia (CLL) or small lymphocytic lymphoma (SLL) is impacted by the type of Bruton’s tyrosine kinase inhibitor used for treatment.
A research team led by Jennifer Brown, Dana-Farber Cancer Institute, Boston, Massachusetts, USA, evaluated PFS in patients with CLL or SLL who were treated with either zanubrutinib or ibrutinib, to determine whether zanubrutinib displayed non-inferiority/superiority compared to ibrutinib. Whilst both zanubrutinib and ibrutinib are Bruton’s tyrosine kinase inhibitors, zanubrutinib has a greater specificity.
A total of 652 patients with a diagnosis of relapsed/refractory CLL or SLL, who had received a minimum of one previous course of therapy, were enrolled and randomised to receive zanubrutinib or ibrutinib, until the end points of either unacceptable toxic side effects or disease progression. Patients were followed up for a median time period of 29.6 months, and at this point, the disease progression or death hazard ratio was 0.65, with a 95% confidence interval of 0.49–0.86 (p=0.002).
PFS rates at 24 months were 78.4% in the zanubrutinib arm compared to 65.9% in the ibrutinib arm. It was also noted that the duration of PFS was longer in patients with TP53 mutation and/or chromosome 17p deletion, who were treated with zanubrutinib compared to those treated with ibrutinib (death or disease progression: hazard ratio: 0.53; 95% confidence interval: 0.31–0.88). Additonally, zanubrutinib was found to have an improved safety profile compared to ibrutinib.
This research highlights how different therapeutics within the same drug class can have different impacts on disease progression, and how understanding the mutation profile in haematological malignancies could aid clinicians in developing personalised treatment regimens by identifying which genetic subgroups respond best to particular therapies.