Acalabrutinib Shows Promising Results for the Treatment of CLL

Jennifer Woyach, MD, an associate professor in the Department of Internal Medicine at The Ohio State University Comprehensive Cancer Center–James, discusses the rationale and efficacy for the phase 1/2 trial of acalabrutinib (Calquence) in patients with chronic lymphocytic leukemia (CLL).

Woyach explains that acalabrutinib is an inhibitor of Bruton’s kinase (BTK), and it's a second-generation covalent inhibitor. Similar to ibrutinib (Imbruvica), it binds irreversibly to BTK, but it is more selective than ibrutinib. Ibrutinib inhibits many structurally similar proteins, while acalabrutinib inhibits less, which is important for toxicity. She thinks that some of the toxicity seen with ibrutinib are because of those alternative targets. Some of the toxicities may lessen with acalabrutinib.

In treatment-naïve and relapsed/refractory disease, the data has looked promising with this agent, according to Woyach. In 1 study with 53 months of follow-up for 99 patients with treatment-naïve CLL, about 86% of the patients were still on treatment, which she says is impressive. The event-free survival at 48 months was 90%. This is looking promising with acalabrutinib, which is similar to what has been seen with ibrutinib in this patient population. Although she says it’s difficult to compare trial to trial, it’s good to see that it looks similar to ibrutinib in this setting.

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