ICML 2023 | The value of zanubrutinib in the CLL treatment armamentarium & SEQUOIA trial updates
Pablo Mozas, MD, PhD, Hospital Clinic Barcelona, Barcelona, Spain, comments on the improving treatment landscape for patients with chronic lymphocytic leukemia (CLL), emphasizing the value of agents including BTK inhibitors and BCL-2 inhibitors. Dr Mozas then goes on to discuss the promising results observed with the use of zanubrutinib, highlighting findings from the SEQUOIA trial (NCT03336333). This interview took place at the 17th International Conference on Malignant Lymphoma (ICML), held in Lugano, Switzerland.
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Transcript (edited for clarity)
So the outcomes of CLL patients have radically changed in the last few years, mainly those of patients with high-risk genetics, deletion 17p, tp53 mutation, IgHV unmutated, and this is mainly due to the approval of small targeted action molecules such as BTK inhibitors and BCL-2 inhibitors. So the first BTK inhibitor to be approved was ibrutinib, which demonstrated improved survival compared to chemoimmunotherapy in three randomized controlled trials in the front-line setting...
So the outcomes of CLL patients have radically changed in the last few years, mainly those of patients with high-risk genetics, deletion 17p, tp53 mutation, IgHV unmutated, and this is mainly due to the approval of small targeted action molecules such as BTK inhibitors and BCL-2 inhibitors. So the first BTK inhibitor to be approved was ibrutinib, which demonstrated improved survival compared to chemoimmunotherapy in three randomized controlled trials in the front-line setting. The second-generation inhibitor acalabrutinib also demonstrated superiority both in the front-line and relapsed/refractory setting with the ELEVATE-TN and the ELEVATE-RR studies, respectively. And now we have another one of the second generation BTK inhibitor, which is also a covalent BTK inhibitor, that is zanubrutinib, which has been approved both in the front-line and relapsed/refractory settings for CLL. So the approval was based on the results of the SEQUOIA trial, which compared zanubrutinib with chemoimmunotherapy in the front-line setting and in the ALPINE study, which compared ibrutinib with zanubrutinib in the relapsed/refractory setting. So the results of zanubrutinib are really encouraging with improved PFS compared even with ibrutinib, which makes zanubrutinib the first inhibitor to improve efficacy compared to first generation BTK inhibitors and also improved safety with reduced cardiovascular events, especially atrial fibrillation, which is a relevant finding. So the longer-term follow-up of the SEQUOIA study has been presented at this congress with a median follow-up of now 3.6 years with improved efficacy compared with chemoimmunotherapy and manageable safety profile. So obviously a step forward in the CLL treatment armamentarium, but we’ll still need to see head-to-head comparisons between acalabrutinib and zanubrutinib to try to decide which is the best treatment for our patients.
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