Dr Shadman on the Utility of a Meta Analysis of BTK Inhibitors in R/R CLL

We believe that this data could be potentially helpful and inform colleagues or researchers in terms of having a better understanding of the relative efficacy of covalent BTK inhibitors [in patients with relapsed/refractory CLL].”

Mazyar Shadman, MD, MPH, an associate professor in the Clinical Research Division at Fred Hutchinson Cancer Center and physician at Seattle Cancer Care Alliance, discussed the utility of network meta analysis (NMA) as a methodological tool for evaluating treatment efficacy of covalent BTK inhibitors in relapsed/refractory chronic lymphocytic leukemia (CLL) when head-to-head clinical trial data are unavailable.

Although randomized controlled trials (RCTs) represent the highest standard of evidence, Shadman explained that in many clinical settings—particularly with emerging therapies—direct comparisons between agents may not yet exist, Shadman noted. In these circumstances, indirect methodologies such as NMA offer a structured and systematic approach to estimate relative efficacy and inform clinical decision-making, he explained.

NMAs utilize statistical modeling to integrate data from multiple randomized trials that share common comparators, allowing for indirect comparisons between treatments that have not been directly tested against each other. Shadman highlighted that this method is particularly useful in therapeutic areas such as relapsed/refractory CLL, where multiple covalent BTK inhibitors are approved but direct comparative data are limited.

Specifically, NMAs evaluating therapies like ibrutinib (Imbruvica), acalabrutinib (Calquence), and zanubrutinib (Brukinsa) can help clinicians and researchers assess relative efficacy across trials even in the absence of direct head-to-head evidence. Shadman emphasized that although NMAs provide valuable insights, they should be interpreted with caution given their non-prospective nature and variations in study design, patient populations, and end point definitions. Nonetheless, he noted that these analyses offer a critical interim solution to guide evidence-based treatment selection and to support future trial design.