VIDEO: ‘Big change’ in CLL with wider array of targeted therapy options

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As I mentioned, we really have seen such a big change in the last 5 years with these targeted therapies. So, we've basically shown that, you know, chemotherapy is no longer the preferred front-line therapy for almost all patients with CLL. And even ibrutinib [Imbruvica; Pharmacyclics/AbbVie, Janssen] now is no longer being used as a preferred therapy because we've shown that the second-generation covalent BTK inhibitors are much more effective, with a better side-effect profile. So now I'd say my new front-line preferred therapy for almost all of my patients is either, one, continuous BTK inhibitor therapy with either acalabrutinib [Calquence, AstraZeneca] or zanubrutinib [Brukinsa, BeiGene], or fixed-duration venetoclax [Venclexta; Genentech, AbbVie] and obinutuzumab [Gazyva, Genentech]. And the decision between those two options really comes down to a couple things. One is cytogenetic and molecular risks. So, for example, we know that patients who have higher risk cytogenetics, like a deletion 17p or a TP53 mutation, those who have unmutated immunoglobulin heavy chain, those patients probably do better with a continuous BTK-inhibitor therapy. Whereas those who really value time off of therapy, maybe a fixed duration with venetoclax, obinutuzumab is better. In patients who have major cardiovascular complications, or they are on medications that increase their risk of bleeding, those patients may want to avoid a BTK inhibitor. Fixed-duration therapy is also a good option there. And then typically I switch between those two options in the second-line setting for patients who have progression of disease or intolerance. And then lastly, pirtobrutinib [Jaypirca, Eli Lilly& Co.] is approved for these patients who are double refractory. So, it's really exciting to have that as a new option.