VIDEO: Recent approvals changing treatment landscape in CLL

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We've had a lot of approvals for CLL in the last couple years. I think the one we're all most excited about was the recent approval in the relapse/refractory setting for pirtobrutinib [Jaypirca, Eli Lilly & Co.], which is a novel class of drugs which are a noncovalent [Bruton tyrosine kinase (BTK)] inhibitor. So, they are reversible binders to BTK. And what’s exciting about this class of drugs is they bind a little bit differently than the currently approved covalent BTK inhibitors, and that’s ibrutinib [Imbruvica; Pharmacyclics/AbbVie, Janssen], acalabrutinib [Calquence, AstraZeneca] and zanubrutinib [Brukinsa, BeiGene].

So, we know right now that if a patient has a resistance mutation to one of those three approved covalent BTK inhibitors, switching between those agents isn't typically recommended. But the cool thing about pirtobrutinib is that it actually is effective in patients who have one of the most common resistance mutations, and that's cysteine 41 s mutation. And so, we actually have longer follow-up data from the most recent conference, American Society of Hematology Conference. So, at 30-month follow-up, patients with prior exposure to the covalent BTK inhibitors, we actually saw a median duration of response of about 18 months, which is really exciting. And I think what is a really important part of this drug is it's effective in patients who are double refractory to both a covalent BTK inhibitor and venetoclax-based therapies. So, they included about, I think around 40% of patients who had prior BCL-2 inhibitor therapy with venetoclax [Venclexta; Genentech, AbbVie], and they actually showed that those patients had a progression-free survival of about 15 months. And historically, you know, most of those patients who were double exposed to both venetoclax and a covalent BTK inhibitor, we typically saw PFS of, you know, about 9 months. So that's a pretty significant jump compared to historical data. So, I think that's one of the most exciting approvals that we just got, and I'm happy I have that option now for my patients.

And in the front-line setting, we've had quite a few approvals in the last few years. You know, the whole landscape for CLL has changed so much in the last 10 years. Ibrutinib was approved in the front-line setting in 2016, and it kind of paved the pathway for targeted agents becoming the new preferred option for patients. Acalabrutinib- and venetoclax-based therapies were approved in 2019 in the front-line setting. And then zanubrutinib was approved just about a year ago. And so that means in the last 5 years, these are now really the preferred treatment options for patients in the first- and second-line setting. And it's been quite a big change. So, it's very exciting to be a CLL doctor right now.