Patients With CLL Maintain DFS Without Continued Targeted Therapy

In part two of this podcast series, Adam Kittai, MD, hematologist and assistant professor of medicine, Ohio State University, highlights findings from the CAPTIVATE study regarding the efficacy of ibrutinib vs placebo for disease-free survival in patients with chronic lymphocytic leukemia.

Listen to part one here.

Read the full transcript:

Welcome back to PopHealth Perspectives, a conversation with the Population Health Learning Network where we combine expert commentary and exclusive insight into key issues in population health management and more.

In part two of this podcast series, Dr Adam Kittai highlights findings from the CAPTIVATE study regarding the efficacy of ibrutinib versus placebo for disease-free survival in patients with chronic lymphocytic leukemia. Dr Kittai?

My name is Dr Adam Kittai. I am from the Ohio State University. I am an assistant professor of medicine here. I am an expert in chronic lymphocytic leukemia.

Specifically, my research involves bringing novel clinical trials to this space and also finding novel therapies for high-risk disease, as well as studying cellular therapies and looking at the Richter's syndrome in CLL.

The CAPTIVATE study was a little bit different venetoclax study. First off, this was a younger patient population. This was aged less than 70 and the design was a little bit different.

All patients received ibrutinib for 3 cycles, then venetoclax plus ibrutinib for 12 cycles, similar to the GLOW trial, but then a randomization event occurred where patients who had undetectable minimal residual disease after the 15 cycles of treatment were put into one cohort of patients versus those who were positive, who were put into another cohort of patients.

We have the final data for the undetectable minimal residual disease group, which compared patients to ibrutinib after completing the combination versus placebo. We don't have all the information for the other combination, which was undetectable minimal residual disease positive, where patients were either randomized to ibrutinib or ibrutinib/venetoclax.

That trial extension hasn't been fully published yet. We're going to talk about the MRD-negative subgroups.

Once again, these patients got 3 cycles of ibrutinib, then ibrutinib/venetoclax for 12 cycles. If they were MRD-negative, they were randomized to either ibrutinib or placebo.

This trial started with 164 patients. Eighty-six patients had undetectable minimal residual disease after combination treatment. Therefore, they were the ones who underwent the randomization.

Interestingly, the one-year disease-free survival after randomization was 95% of the placebo arm and 100% in the ibrutinib arm. There was no difference between one-year disease-free survival, which was the primary endpoint.

This is really exciting to see, because it justifies an all-oral, nonchemotherapy treatment in the upfront setting for treatment of patients with CLL. It does not look like continuation with ibrutinib, if you attain an undetectable minimal residual disease status, is necessary moving forward. I think we were all excited about that.

One of the other couple things about this study that was interesting is that they had higher rates of undetectable minimal residual disease in the marrow compared to the GLOW trial. There was a 70% rate. Also, the [adverse events] looked pretty good in this trial too, with less than 10% of patients having to discontinue due to AE developments.

I think part of that reason that maybe the AEs might appear better than GLOW—although, obviously, it's hard to do a cross-trial comparison, and we don't have all the data from GLOW just yet—is that this was a younger patient population.

I think that both of these studies are exciting, as they are evaluating a very similar/equal treatment regimen, ibrutinib plus venetoclax. I think that this will be a combination that people will definitely consider for treatment-naive patients, especially in the younger population.

Thank you, Dr Kittai. You already mentioned how it's going to filter into practice. Is there anything additional you wanted to say about how it'll impact clinical practice?

Moving forward, the question is, how will this impact clinical practice? I think that the patients who are eligible to be receiving venetoclax plus obinutuzumab now are going to be really challenged by this treatment. I think that as a provider, you're going to be debating whether or not to use ibrutinib plus venetoclax versus venetoclax plus obinutuzumab.

I think that that's where the question really lies. I think that the trial that we're all eagerly awaiting is CLL17, which is ibrutinib versus venetoclax plus obinutuzumab versus ibrutinib plus venetoclax. That will be definitive trial that will determine superiority of our front-line treatments.

Going forward, as this landscape continues to change and more research comes out, what would you say people seeking to cover these drugs should know about ibrutinib?

I would say that ibrutinib continues to be a very well-tolerated medication, and even when it's combined with venetoclax in a younger population specifically, it also continues to be very well-tolerated, leading to deep remissions and hopefully, long remissions with higher rates of undetectable minimal residual disease.

Even though ibrutinib was the first BTK inhibitor to be approved for the treatment of CLL, I think it continues to be a strong contender and a great medication.

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