CLL Trial Insights: Targeted Therapy Risks and Outcomes

In an interview with Blood Cancers Today, Nicole Lamanna, MD, Professor of Medicine and Director of the Chronic Lymphocytic Leukemia (CLL) Program at Columbia University Medical Center, discusses results from a network meta-analysis evaluating Bruton tyrosine kinase (BTK) inhibitors in patients with relapsed/refractory CLL with high-risk cytogenetic features, including del(17p), TP53 mutation, and del(11q) as well as two real-world studies exploring adverse events from CLL therapy.

The meta-analysis incorporated data from 3 randomized clinical trials: ALPINE (zanubrutinib vs ibrutinib), ELEVATE-RR (acalabrutinib vs ibrutinib), and ASCEND (acalabrutinib vs investigator’s choice). Unlike traditional meta-analyses, the network meta-analysis framework enabled both direct and indirect comparisons of multiple therapeutic agents with a shared comparator.

Dr Lamanna emphasized the significance of cardiovascular safety in CLL management, particularly in an older population where hypertension and arrhythmias are common. Real-world retrospective data from 2019 to 2023 were also examined to assess baseline hypertension and treatment-emergent cardiovascular events across patients treated with ibrutinib, acalabrutinib, or zanubrutinib. Approximately 50% of patients in each cohort had pre-existing hypertension at treatment initiation. Findings demonstrated a higher incidence of new-onset or worsening hypertension in the ibrutinib group compared with second-generation BTK inhibitors.

These results align with previous evidence suggesting a lower rate of cardiovascular adverse events—such as atrial fibrillation and hypertension—with acalabrutinib and zanubrutinib. Dr Lamanna concluded that these safety differentials may inform treatment selection, favoring second-generation agents in appropriate clinical settings.

This discussion highlights the evolving role of safety profiling in targeted therapy selection for CLL, particularly for patients with high-risk features and comorbid cardiovascular conditions.