Commentary

Video

Dr Ryan Jacobs Highlights Sustained Success in Patients With CLL Through 1-Year Treatment Plan

Ryan Jacobs, MD, of Atrium Health Levine Cancer Institute, explains that the phase 2 CAPTIVATE study's fixed-duration treatment cohort shows long-term progression-free survival for patients with chronic lymphocytic leukemia (CLL) who received the first-line treatment of ibrutinib and venetoclax.

Ryan Jacobs, MD, lymphoma division director at Atrium Health Levine Cancer Institute, explains that the phase 2 CAPTIVATE study's fixed-duration treatment cohort shows that most patients with chronic lymphocytic leukemia (CLL) remain progression-free after an average of 4 and a half years off the first-line treatment of ibrutinib and venetoclax. Also, he believes future trials should focus on patient responses to subsequent therapies to optimize treatment sequencing.

Jacobs presented this abstract, "Outcomes in High-Risk Subgroups After Fixed-Duration Ibrutinib + Venetoclax for Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma: Up to 5.5 years of Follow-Up in the Phase 2 CAPTIVATE Study," at the European Hematology Association (EHA) 2024 Congress in Madrid, Spain.

Transcript

Could you summarize the key findings of the phase 2 CAPTIVATE study?


So, of course, CAPTIVATE has been presented several times, and we keep updating the data as we get longer follow up. There was actually 2 components of the phase 2 study, there were 2 arms. This presentation that I presented at EHA is the fixed-duration cohort where all patients just received treatment for the combined 1 year and stopped. There was a different arm of the study where it was MRD [minimal residual disease]-directed in terms of people that did and did not stop treatment, but this was the fixed-duration cohort.

This was now 5 and a half years worth of data to present on how these patients did. What's exciting is that even 5 and a half years of follow up, so this is an average of 4 and a half years off of treatment now, there still is not a median progression-free survival that has been reached; the majority of patients still have not had their disease progressed, and that includes even the high-risk patients identified as having chromosome 17 aberrations.

Also, the unmutated ighV [immunoglobulin heavy-chain variable region gene] patients still have not had a median progression-free survival. So, these are really excellent outcomes in a time-defined regimen for patients even with high-risk disease.

There does appear to certainly be some separation in the outcomes that you can see forming. The favorable mutated patients, 80% of them are still free of progression. The higher-risk patients, for example, the patients with chromosome 17 aberrations, around 54% are still free of progression. So, certainly some differences there, but, evidently, it is a really effective treatment option for all patients with CLL, it seems.

How can future trials build off these findings? What should they focus on?

I think we're all interested, as more patients ultimately progress and need additional therapies, we want to know how those patients are going to respond. We've already seen some data from CAPTIVATE come out, and this longer follow up has supported that when these patients progress, ultimately they do not have recognizable resistant mutations present on CLL cells that have been analyzed.

Therefore, it is showing with that lack of resistance mutations what we're now seeing, clinically that you can reach challenge with BTK [Bruton tyrosine kinase]; it's effective in the majority of patients, close to 80% will respond. Then, there's also been reached challenges with the combination of BTK and venetoclax. Those patients, the majority, are responding, as well.

So, I think as we have more progressive events, we want to know how these patients are going to do long term, even with their next treatments that occur. As we all know, treating CLL is a marathon, so we want to see how the sequencing of treatment goes. I think, ideally, we're going to be able to manage most patients simply by just rechallenging when we need to.

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