Newly Diagnosed CLL: BTK Inhibitor Monotherapy

A discussion on the use of BTK (Bruton’s tyrosine kinase) inhibitor monotherapy for newly diagnosed chronic lymphocytic leukemia (CLL) patients, with special consideration of the RESONATE trial regimen.

Cody Steeves, PharmD, BCOP: Moving forward, we can discuss the use of BTK [Bruton’s tyrosine kinase] inhibitor monotherapy in CLL [chronic lymphocytic leukemia], in newly diagnosed, or sometimes not newly diagnosed. Should this be a standard for all patients? We can review the RESONATE trial here as well with that.

Alison Duffy, PharmD, BCOP: I'll talk about ibrutinib. But I'd love to hear your thoughts on some of the other agents, too. You mentioned the RESONATE trial, and this was really the first trial for our BTK inhibitors where the larger class of small molecule inhibitors, which also includes venetoclax for the sake of this talk today—and regarding the RESONATE trial, we have recently seen a 6-year survival follow-up data showing the long-term benefit with ibrutinib.

So I think it's really exciting to see some of that data being even more confirmatory in the relapsed/refractory setting for ibrutinib. In the upfront setting, or newly diagnosed setting, the RESONATE-2 trial with ibrutinib also establishing ibrutinib as the first-line choice for patients that were older and those patients without deletion of 17P, showing us that significantly longer progression-free survival [PFS] benefit seen across all those high-risk subgroups such as those with deletion of 17P.

I think that, in combination with the ALLIANCE 041202 trial, again in older patients confirming these results in over 500 patients, I think that leading to the FDA approval and that preferred Category 1 recommendation for those older, frail patients, or those younger patients with comorbidities, had really shaped the role of ibrutinib in the front-line setting.

Then more recently with the E1912 trial, which looked at the combination of ibrutinib with rituximab as first-line therapy for younger patients, showing especially, for those unmutated IgHV [immunoglobulin heavy chain gene] CLL patients, replacing the FCR [fludarabine cyclophosphamide rituximab] regimen specifically for this patient population, I think is a really big change. I do think it's important to think about the fact that ibrutinib is not for everybody, and not everybody's a candidate for oral chemotherapy, as we've already mentioned, but also might not be a great candidate for ibrutinib based on cardiac history.

So if you have a patient—at least from my perspective—if you have a patient with uncontrolled atrial fibrillation, has a really high risk of bleeding that can't be mitigated, or uncontrolled hypertension despite optimizing therapy management, ibrutinib wouldn't be my first choice.