Continuous zanubrutinib vs. fixed-duration VenO for newly diagnosed CLL

The efficacy and safety of continuous zanubrutinib in treatment-naïve chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) has been established in the pivotal SEQUOIA trial. Similarly, the combination of fixed duration venetoclax and obinutuzumab (VenO) has been evaluated in the CLL14 study. In the absence of a head-to-head comparison of both treatment regimens, however, it is challenging for physicians to make an informed choice between these two treatment options in clinical practice. To provide some more guidance for clinicians, Prof Dr Talha Munir (Leeds Teaching Hospitals NHS Trust, Leeds, UK) and colleagues performed an unanchored, matching-adjusted indirect comparison (MAIC) between continuous zanubrutinib and fixed duration VenO using data from SEQUOIA and CLL14. According to this analysis, continuous zanubrutinib was associated with a longer progression free survival (PFS) (HR _PFS-INV[95%CI]: 0.66[0.44-0.97]; p= 0.0351) and a trend for a better overall survival (OS) (HR_OS[95%CI]: 0.89[0.55-1.46]; p= 0.6468) compared to VenO. Similar findings were obtained when only patients with an unmutated IGHV status were considered.

While these data suggest a better efficacy for continuous zanubrutinib over fixed duration VenO in treatment-naïve CLL/SLL patients, the limitations of an indirect, cross-trial comparison warrant that these results are interpreted with caution.