Clinical Impact of the RESONATE-2 Trial in CLL

John Fox, MD, MHA: In 2016, Barr published an extension study of RESONATE-2 that looked at the extension of the RESONATE-2 study that was published in 2014. And what they showed, interestingly, was that there was an 88% reduction in the risk of progression or death and, furthermore, patients were able to tolerate that therapy. There was just a 12% discontinuation rate. I think it was 10% of patients who had atrial fibrillation; 7% of patients had a major hemorrhage. But in general, therapy was well tolerated, and patients had, again, that 88% reduction in the risk of progression or death.

The RESONATE-2 trial compared ibrutinib with chlorambucil, a chemotherapy agent that has known toxicities. Tedeschi looked at patient-reported outcomes 3 years out after patients were initiated therapy in RESONATE-2 and found that, in general, patients who were on ibrutinib had better patient-reported outcomes and better quality of life, both related to their treatment as well as overall. What does that mean to a health plan or a payer for these therapies?

In general, the decision on which therapies are going to be better tolerated and give the patients what’s more important to them—improved quality of life—were really left to the provider. Typically, we don’t make treatment decisions based on patient-reported outcomes because it’s hard to compare 1 trial with another. And in this trial in particular, chlorambucil, which was the comparator group and was chosen at the time that ibrutinib was first being studied, is no longer considered a standard of care. So, although it’s important that patient-reported outcomes are improved compared with chlorambucil, it really is not germane anymore, because chlorambucil is not considered the standard of care.

If, for example, there was a head-to-head study of ibrutinib compared with venetoclax and 1 had better patient-reported outcomes compared with another, again, that would be a treatment decision left to the patient and provider, not the health plan.