VIDEO: Recent advancements in CLL

Editor’s note: This is an automatically generated transcript. Please notify editor@healio.com if there are concerns regarding accuracy of the transcription.

We're in an interesting place where after a lot of advances in terms of new drug approvals, we, coming into 2023 had actually not had a new drug approved for CLL since 2019. We've hit a little bit more of a stagnant point in terms of new drug approvals. At the beginning of 2023, we did get zanubrutinib (Brukinsa; BeiGene) approved. This wasn't necessarily a breakthrough in terms of giving us a new target to go after and treat, but it does give us an additional option for inhibiting BTK, which we historically had done with ibrutinib (Imbruvica; Janssen, Pharmacyclics) and more recently had been doing with acalabrutinib (Calquence; AstraZeneca) after acalabrutinib had shown superior tolerability to ibrutinib. So what zanubrutinib does is give us an additional BTK inhibitor option and it had also an interesting head-to-head comparison to ibrutinib where it actually showed not only superior tolerability like acalabrutinib did to ibrutinib, but also superior efficacy. And there's, of course, no direct comparisons to zanubrutinib and acalabrutinib. So at this point, you know, both acalabrutinib and zanubrutinib are considered to be, you know, good options and it's nice that we now have, you know, more than one, quote, unquote, "second generation BTK inhibitor options."

I think most of us expected pirtobrutinib (Jaypirca, Eli Lilly & Co) to be approved this year. It has, as of this recording, has not yet received FDA approval. The drug is available though because it's approved in relapsed refractory mantle cell lymphoma and it is on the NCCN guidelines. So many, including myself, have been able to use it in patients that really need it based on that NCCN approval and availability in mantle cell, we can get it off-label in CLL. But I suspect any day now we will have pirtobrutinib available.

And as I understand it, its initial approval will be for patients that have been previously treated with both covalent BTK inhibitors, which is ibrutinib, acalabrutinib, zanubrutinib, and have been treated with venetoclax (Venclexta; AbbVie, Genentech), so it's kind of for the, quote, unquote, "Double refractory patient population." That, I think, will be a really big breakthrough to have that officially available for our CLL patients. It does give us a new kind of line of therapy that beyond just covalent BTK and BCL2 with venetoclax. So the difference between pirtobrutinib and the other BTK inhibitors is it's a non-covalent BTK inhibitor that binds irreversibly to Bruton's tyrosine kinase at a site different from that of ibrutinib, acalabrutinib, and zanubrutinib. It has data that shows efficacy in patients that have been treated on and have even become resistant to those prior BTK inhibitors so that will give us an additional line of therapy to treat our CLL patients with.