The Role of Older and Newer BTK Inhibitors in CLL


Thomas James Kipps, MD, PhD, discusses the role of later generation and newer generation burton tyrosine kinase inhibitors in patients with chronic lymphocytic leukemia.

Thomas James Kipps, MD, PhD, deputy director of research operations for UC San Diego Moores Cancer Center at UC San Diego Health, discusses the role of older generation and newer generation Bruton’s tyrosine kinase inhibitor’s (BTKi) for patients with chronic lymphocytic leukemia (CLL).

As a part of the Society of Hematology Oncology 2022 meeting, Kipps looked ahead to the wider landscape of CLL and how new generation BTKis have built on previous generations of treatment.

In an interview with Targeted OncologyTM, Kipps discusses overcoming treatment resistance in this patient population and how BTK inhibitors like ibrutinib (Imbruvica), acalabrutinib (Calquence), zanubrutinib (Brukinsa), work to do that. Since the accelerated approval of ibrutinib in 2014, these BTK inhibitors have opened targeted treatment for patients with CLL who may have certain mutations or other factors that impact their treatment plan.


0:07 | In the case of the BTK inhibitors, we know that the covalent inhibitors are very much affected by a specific mutation in BTK at position 481, which, when it happens, prevents the drug from binding and forming a chemical bond with BTK. If you interchange between the different drugs, you're not going to have success in treating that patient if that mutation exists. I will say this [though], that ibrutinib does have some activity against the cells that have this mutation in them, although the cells may be coming up, but you can keep patients almost in check, but the some of the newer BTKs, such as acalabrutinib or perhaps zanubrutinib, may be less effective in holding down that clone.

0:50 | So sometimes, one can buy some time by maybe switching over to Ibrutinib if you don't have access to the noncovalent inhibitors, which I think that's important to note. I [also] think that if you do have such resistance, obviously you have to look at either these 3rd generation BTK inhibitors such as the non-covalent inhibitors, or perhaps to try a venetoclax based regimen that can be effective, along with maybe perhaps an anti-CD20 [drug] if you have to debulk the tumor to prevent or mitigate the risk of tumor lysis [syndrome].

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