Dr Shadman on the Comparative Efficacy of Currently Available BTK Inhibitors in CLL

Mazyar Shadman, MD, MPH, Innovators Network Endowed Chair, associate professor, Clinical Research Division, Fred Hutch Cancer Center; associate professor, Medical Oncology Division, University of Washington School of Medicine, discusses results from a network meta-analysis on the comparative efficacy of BTK inhibitors in the treatment of patients withrelapsed/refractory chronic lymphocytic leukemia (CLL).

Notably, these data were shared at the 2024 ASCO Annual Meeting. Investigators first examined the overall response rates (ORR) and complete response (CR) rates with zanubrutinib (Brukinsa) vs ibrutinib (Imbruvica) in this patient population, Shadman begins. The findings indicated that the ORR significantly favored zanubrutinib, he says. Although CR rates numerically favored zanubrutinib, this difference did not reach statistical significance, Shadman explains. Similarly, when comparing zanubrutinib with acalabrutinib (Calquence), neither the ORR nor the CR rate were significantly different between the 2 groups, he notes.

Next, investigators analyzed progression-free survival (PFS), focusing on high-risk populations. In this analysis, zanubrutinib was shown to be over ibrutinib, acalabrutinib, and chemoimmunotherapy, regardless of whether adjustments were made for COVID-19-related deaths, Shadman elucidates.

When limiting the PFS analysis to patients with 17p deletions, zanubrutinib again showed superiority over ibrutinib, acalabrutinib, and chemoimmunotherapy in the adjusted model, he continues. However, it is important to note that in the unadjusted model, no significant difference was observed between zanubrutinib and acalabrutinib, according to Shadman. This indicates that although zanubrutinib may be beneficial for patients with 17p deletions, the extent of its advantage depends on whether adjustments are made for specific variables, Shadman notes.

In terms of overall survival (OS), there was a numerical trend favoring zanubrutinib across comparisons with ibrutinib, acalabrutinib, and chemoimmunotherapy, he expands. However, these findings indicate that although zanubrutinib may offer some benefits in terms of OS, these advantages are not strong enough to be considered statistically significant at the time of this analysis, Shadman concludes.