A recent network meta-analysis comparing novel targeted therapies for relapsed or refractory chronic lymphocytic leukemia (R/R CLL) indicates similar and favorable safety profiles among venetoclax combined with rituximab, acalabrutinib, and zanubrutinib. The analysis, published in Therapeutic Advances in Medical Oncology, offers insights into the comparative safety of these treatments in a challenging patient population.
The study, conducted by researchers from Poland’s Jagiellonian University, addressed the increasing need to understand the safety profiles of new targeted therapies in often heavily pretreated patients with CLL. The investigators performed a systematic review of trials involving patients with R/R CLL, identifying 14 randomized trials that met the inclusion criteria, with at least 80% of participants having R/R CLL.
Comparative Safety Analysis
While the overall incidence of adverse events (AEs) did not significantly differ among the therapies, bendamustine plus rituximab showed a lower risk of grade 3 or higher AEs compared to ibrutinib (RR, 0.62; 95% CI, 0.40-0.86), acalabrutinib (RR, 0.69; 95% CI, 0.45-0.94), zanubrutinib (RR, 0.64; 95% CI, 0.42-0.91), and venetoclax plus rituximab (RR, 0.87; 95% CI, 0.79-0.96). Acalabrutinib, zanubrutinib, and venetoclax plus rituximab exhibited similar frequencies of grade 3 or higher AEs, serious AEs, and treatment discontinuations due to death.
BTK Inhibitor Specifics
Notably, the analysis revealed that zanubrutinib was associated with a higher risk of hypertension (RR, 2.96; 95% CI, 1.74-5.16) and bleeding (RR, 1.38; 95% CI, 1.06-1.81) compared to acalabrutinib. This finding aligns with previous research suggesting that second-generation BTK inhibitors like zanubrutinib and acalabrutinib have improved cardiac safety profiles compared to first-generation inhibitors like ibrutinib. A prior study demonstrated that zanubrutinib resulted in fewer discontinuations due to AEs and fewer cardiac events compared to ibrutinib.
Implications for Clinical Practice
The study authors acknowledged differences in data collection and reporting across the included studies and noted wide confidence intervals in some comparisons. They emphasized the need for longer-term research to comprehensively evaluate the safety profiles of these therapies. However, the current data suggest that acalabrutinib, zanubrutinib, and venetoclax plus rituximab have relatively similar safety profiles, potentially making them preferable options for patients with R/R CLL.
