Ibrutinib in Younger, but Unfit Patients

Steven Coutre, MD:In an academic center, we’re often referred younger patients, not your typical older patient, but somebody who’s quite young for their disease. I’ve actually seen patients as young as in their 20s. A more typical patient might be somebody in their late 50s who is diagnosed and often doesn’t need treatment initially, but eventually will come to need treatment, and they’re still young. Of course, people can have significant comorbidities. In the trials, that’s measured by what we call the Cumulative Illness Rating score, the CIR score, which I’m not a big believer in. It’s pretty easy to determine whether somebody is truly fit for a chemoimmunotherapy regimen or not. Do they have poorly controlled hypertension? Are they overweight? Do they have diabetes? You add up those risk factors, and it’s pretty easy to decide whether you’re thrilled about giving somebody a more intensive regimen, which might cause neutropenia and lead to infections. There isn’t anything really objective that I add up to make that decision.

The other factor that can play a role here, too, is renal function. A lot of our standard drugs are renally cleared. So, in those with chronic kidney disease, one has to be particularly careful about giving some of our chemotherapy drugs because they’d be more prone to myelosuppression and, therefore, more prone to infections.

For a younger, unfit patient, a drug like ibrutinib would be a very good option, as well, from the standpoint of focusing on the tolerability, the safety aspect. You’re confident that you’re going to be able to deliver the therapy in that patient without having to interrupt because of complications, and therefore you’re confident you’re going to get the full therapeutic benefit. In the trials, including the RESONATE 2 trial, we weren’t treating patients under 65. But it’s commercially available. And in other trials that are ongoing, we have used it in this population. For example, there is a large national trial with patients under the age of 70, FCR (fludarabine/cyclophosphamide/rituximab) versus ibrutinib plus rituximab. That trial has accrued over 500 patients; it’s fully accrued. We’ve treated patients on that trial, so we’ll wait and see what that shows.

Case Scenario:Ibrutinib in Younger, Unfit Patients with Newly-Diagnosed CLL