Patient Selection for Upfront Ibrutinib

Steven Coutre, MD:Ibrutinib was approved several years ago for patients with CLL who have had prior treatment. It also was approved for initial treatment if patients had deletion 17p, but that’s uncommon at presentation. Because of the RESONATE-2 trial, it very recently received approval for initial treatment of patients with CLL. That really broadens our ability to use the drug in patients as up-front therapy. With an FDA approval, it’s much easier to obtain it for a patient, from an insurance perspective. In our practice, where we’re largely doing clinical trials, that’s not as relevant. For a patient treated in the community, it’s all about what they’re able to obtain, as well. We’ve seen with the approval in the frontline setting, that it’s quite easy to access the drug for an appropriate patient. In our treatment algorithm overall, it’s really being integrated in the context of a trial or in standard practice for pretty much all patients. It gives you another very good option when you’re making that decision about what’s most appropriate for that individual patient.

Physicians often ask, “What do we do after ibrutinib? What if a patient progresses?” Fortunately, that’s not been all that common. There are some published data on that, but one has to be very careful about interpreting that data because that study involved heavily pretreated patients who were receiving ibrutinib. In many cases, they had exhausted all prior conventional therapy and had quite advanced disease. That’s a very different patient receiving ibrutinib than someone receiving it as initial therapy or even as second-line therapy after an FCR (fludarabine/cyclophosphamide/rituximab) regimen. Those patients didn’t do well, and that’s not a surprise, because they didn’t have other treatment options.

For someone receiving it earlier, I would argue two things. First, we do have other treatment options for them, including newer oral drugs, as well. Second, it’s a very different patient population, and the progression is going to be much less common. Also, those patients will respond to subsequent therapies, whether they be traditional chemoimmunotherapy or other novel targeted agents. The idea that you want to hold back your best for later, if you’re calling ibrutinib your best, I think you have to move beyond. There’s nothing wrong with using your best therapy initially.

Steven Coutre, MD, shares insights into his approach to frontline therapy for chronic lymphocytic leukemia