Exciting Studies at ASH Surrounding CLL

Thomas J. Kipps, MD, PhD: We’ve had a very exciting ASH. The work on these targeted therapies is quite exciting. Although they’re not being introduced for the first time, we’re coming to understand how to use them best in treating patients with chronic lymphocytic leukemia (CLL) and lymphomas. And it’s very exciting to see long-term follow-up data, which are showing how well these drugs are tolerated and how patients do on therapy. It has clearly been an advance that we’re all very excited about.

One of the aspects that we’ve been able to discuss at this meeting is the work done on understanding what are the mechanisms whereby patients may develop resistance to these drugs. I think it’s very important work, so that we can now begin to understand what type of patients might be those that might be at higher risk for developing resistance. And what’s clear is that some of the risk factors that we considered so important before are falling by the wayside.

For example, we all should know that patients who have deletion in the short arm of chromosome 17 are at increased risk for having a poor response to conventional chemotherapy. With the newer targeted therapies, the outcome is by far not so oblique for these patients, as they can respond as well, sometimes as well as patients who do not have that genetic lesion. And it’s also particularly noticeable for patients who have a deletion in chromosome 11, which is typically associated with a very short time of being in remission after chemotherapy.

Right now, with the new targeted therapies, we’re seeing that patients with these genetic lesions not only do as well, but in the case of the 11q minus, patients appear to be doing better. This is the result of looking at some of the long-term follow-up data from 3 very important trials that were done with ibrutinib. First, the RESONATE trial, comparing ibrutinib with ofatumumab, showed ibrutinib was superior to ofatumumab in terms of the progression-free survival of patients. But, also, the HELIOS study showed ibrutinib combined with bendamustine and rituximab. And then later, the RESONATE follow-up study was a frontline study of patients who were ages 65 and older treated with ibrutinib versus those treated with chlorambucil. Again, that study showed a superiority of ibrutinib over conventional chemotherapy, such as chlorambucil, and allowed for the registration of ibrutinib for use in frontline therapy for patients with CLL.

What’s clear though is you can look at the data and how patients faired, and some of these genetic lesions that I mentioned to you before are actually coming to be not so much a bad risk factor after all. I’ve always advocated that a patient doesn’t have bad disease or a bad prognosis, all they have is bad medicine. If we have better medicine, we can turn a bad prognosis into actually a good type of therapy.