Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL) are two closely related types of white blood cell cancers that are typically diagnosed in older adults. As of 2024, at least 20,000 new cases are reported each year in the United States, with annual deaths exceeding 4,400.
While both CLL and SLL have a relatively high 5-year survival rate of 85%, complications can happen. Mutations in genes like TP53 and related events like 17p deletion can transform CLL/SLL into more aggressive forms of leukemia.
B-cell cancers like CLL and SLL are often caused by abnormal activation of an enzyme called Bruton’s Tyrosine Kinase (BTK). In 2013, Ibrutinib became the first FDA-approved BTK inhibitor for the treatment of CLL/SLL in the US.
Although more effective than previous drugs, Ibrutinib also came with an increased risk of stroke, heart failure, and other dangerous cardiac issues. Now, patients have a safer option – Zanubrutinib (Brukinsa), a second-generation BTK inhibitor developed by the multinational oncology firm BeiGene.
In the large-scale SEQUOIA clinical trial, Zanubrutinib offered a 71% reduction in the risk of disease progression or death compared to Rituximab, another common anti-CLL drug. When the ALPINE trial pitted it against its predecessor, Ibrutinib, Zanubrutinib was found to be superior, with better anti-cancer action and far fewer side effects.
Remarkably, Zanubrutinib also worked exceptionally well in patients with TP53 mutations and 17p deletions in the Alpine trial. Based on these results, the FDA approved Zanubrutinib for the treatment of CLL and SLL in January 2023. The drug has also been approved for treating other B-cell cancers like Mantle Cell Lymphoma and Waldenstrom’s Macroglobulinemia.
