Dr Shadman on Indirect Data for Zanubrutinib vs Acalabrutinib/Venetoclax in Treatment-Naive CLL

“Patients care about efficacy. This study is a source of information that I share with patients who are more focused on efficacy.”

Mazyar Shadman, MD, MPH, a professor in the Clinical Research Division, medical director of Cellular Immunotherapy, and Innovators Network Endowed Chair at Fred Hutch Cancer Center, discussed data from a post hoc analysis that indirectly compared data for zanubrutinib (Brukinsa) from the phase 3 SEQUOIA study (NCT03336333)and acalabrutinib (Calquence) plus venetoclax (Venclexta) from the phase 3 AMPLIFY trial (NCT03836261) for patients with treatment-naive chronic lymphocytic leukemia (CLL).

Shadman began by highlighting the data that was found from the indirect comparison in terms of efficacy. To conduct the analysis, investigators looked at a population of fit patients from SEQUOIA who had a creatinine clearance of at least 50 mL/min, a cumulative illness rating scale score of no more than 6, and no 17p deletions or TP53 mutations; this group was then compared with the population of AMPLIFY. Data from the indirect comparison published in Blood Advances showed that patients from SEQUOIA who received zanubrutinib (n = 123) achieved improved progression-free survival (PFS) vs those from AMPLIFY who were treated with acalabrutinib plus venetoclax (n = 291; HR, 0.47; 95% CI, 0.28-0.77; P = .003). In an unadjusted analysis, patients who received zanubrutinib experieced a 3-year investigator-assessed PFS rate of 89.2% compared with 78.9% for those who received acalabrutinib plus venetoclax. Moreover, overall response rates and complete response rates were 97.6% and 18.7% for zanubrutinib compared with 96.9% and 14.8% for acalabrutinib plus venetoclax, respectively.

Shadman acknowledged that these outcomes may not be surprising, with a continuous therapy like zanubrutinib yielding a higher PFS rate vs a fixed-duration approach with acalabrutinib plus venetoclax. Shadman noted that there are benefits to fixed-duration therapies like acalabrutinib plus venetoclax, but such benefits were beyond the focus of the analysis.However, he still emphasized the importance of publishing these data to add further evidence to help guide treatment selection in the frontline setting for patients with CLL. Ultimately, Shadman pointed out this analysis study provides him with a concrete source to aid in patient care and treatment decision-making, which to point to when treating with patients who prioritize efficacy in their treatments and are willing to receive continuous BTK inhibitor therapy until disease progression.