Dr Ermann on Real-World Data for Zanubrutinib vs Acalabrutinib in Older CLL

“[Differentiating between acalabrutinib and zanubrutinib] have been a burning question in the CLL community. Now, with long enough follow-up and a high sample size, we’re starting to see some differences [between the BTK inhibitors]. In this study, we showed that zanubrutinib actually has better TTNT, [rates of] discontinuation, and OS compared [with] acalabrutinib.”

Daniel Ermann, MD, an associate professor in the Division of Hematology and Hematologic Malignancies and the physician lead of the Chronic Lymphocytic Leukemia (CLL) Clinical Trials Program at Huntsman Cancer Institute, discussed data from a real-world analysis comparing first-line zanubrutinib (Brukinsa), acalabrutinib (Calquence), and ibrutinib (Imbruvica) in the treatment of older patients with CLL, which were presented at the 2026 ASCO Annual Meeting. Ermann also dived into how these data both answer long-standing questions in the CLL field that clinical trials often fail to address and inform clinical practice moving forward.

Data from the analysis showed that patients who received zanubrutinib and were Medicare beneficiaries (n =3006) experiuenced a median time to treatment discontinuation (TTD) that was not reached (NR; 95% CI, NR-NR) vs 24 months (95% CI, 22-25) and 14 months (95% CI, 13-15) for acalabrutinib (n = 4309) and ibrutinib (n = 3208), respectively. Respective times to next treatment (TTNT) were NR (95% CI, 45-NR), 40 months (95% CI, 38-42), and 30 months (95% CI, 29-32) for zanubrutinib, acalabrutinib, and ibrutinib. Additionally, the median overall survival (OS) for each group was NR.

Ermann began by underscoring the value of real-world data and analyses, especially considering the resources, funding, and time required to perform prospective studies. With proper execution and data, real-world analysis can help to inform the gaps where prospective studies are not feasible, he added. In the absence of head-to-head prospective trials comparing BTK inhibitors, the real-world study showed that TTD, TTNT, and OS were all improved with zanubrutinib vs acalabrutinib, findings with the potential inform clinical practice, he said.