Chronic Lymphocytic Leukemia with Steven Coutre, MD Case 1 - Episode 2

Upfront Ibrutinib: RESONATE-2 Trial

Steven Coutre, MD:The RESONATE-2 trial is a randomized phase III trial for previously untreated patients who needed therapy by our traditional criteria, but had not previously had any treatment for their CLL. It compared a drug, chlorambucil, which has been around a long time, which some would consider standard-of-care in older patients, versus ibrutinib. The trial was limited to older patients, those over 65 years. We often use that cutoff, since the average CLL patient is in their 70s. Therefore, it is very realistic to look at that population. The trial simply asked the question, if one treatment was better than another, with the primary endpoint being progression-free survival, did patients do better for a longer period of time?

There’s other secondary endpoints, such as response rate and safety. What this study showed was a very significant difference between the two treatment arms in favor of ibrutinib. Progression-free survival was significantly longer. Even with fairly short follow-up of the study, a median follow-up of about 18 months, there was an overall survival advantage. People lived longer if they received ibrutinib as their initial therapy. From a safety perspective, there was really no difference across the board, certainly no increased safety concerns with the use of ibrutinib. Chlorambucil is a bit more myelosuppressive, so you see more effects on the blood counts. In contrast, with ibrutinib, you usually see very prompt and very sustained improvements in cytopenia, which often are problematic and often are the reason to start therapy in patients with CLL. From the perspective of bringing a better therapy, better in terms of responses, better in terms of tolerability, better in terms of something that’s easy for our patients to use, it really kind of met all of those criteria.

In addition, in the study, we had patients between ages 65 and 70, and then we had those 70 and older. Those 70 and older would be an average CLL patient who is starting therapy, and we saw benefit in both groups. There really was no distinction. It also speaks to the fact that it’s well tolerated. Often patients who are older have more comorbidities, such as diabetes and hypertension, which didn’t impact either the efficacy or the tolerability of the treatment.

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