RESONATE-2 Trial: Safety and Efficacy Updates

Steven Coutre, MD: The RESONATE-2 trial is a randomized phase III trial for previously untreated patients; patients who needed therapy by our traditional criteria, but had not previously had any treatment for their CLL. And it compared a drug, chlorambucil, which has been around a long time and which some would consider standard of care in older patients, to ibrutinib. The trial was limited to older patients, those over 65. We often use that cut-off. And, again, remember, that is the average CLL patient, somebody in their 70s. So, I think it’s very realistic to look at that population. And it 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 are other secondary endpoints like response rate and, of course, 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. And, even with fairly short follow-up of the study, there was 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. And, in contrast, with ibrutinib, you see usually very prompt and very sustained improvements in cytopenias, which often are problematic and often are the reason to start therapy in patients with CLL.

From the perspective of, are we 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 met all of those criteria.

In addition, in the study, we had patients between the ages of 65 and 70, and then we had those 70 years and older. Again, those patients 70 years and older would be an average CLL patient who’s 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. So, often patients who are older, of course, have more comorbidities—diabetes, hypertension, the usual things that we see. And that didn’t impact either the efficacy or the tolerability of the treatment.