William Wierda, MD, Professor, Department of Leukemia, The University of Texas MD Anderson Cancer Center, presented data from the phase 2 CAPTIVATE study during the ASH Annual Meeting & Exposition. The data analyzed patients who received ibrutinib plus venetoclax as first-line treatment for chronic lymphocytic leukemia/small lymphocytic lymphoma. Specifically, Dr. Wierda discussed one-year disease-free survival results from the cohort of patients with minimal residual disease (MRD).

DocWire News: What prompted you to undertake this study?

Dr. Wierda: This was a study, sponsored by Pharmacyclics, to evaluate combination therapy with targeted agents ibrutinib plus venetoclax to evaluate the depth of remission with a fixed duration treatment, and to determine if patients could be given a reasonable time off treatment, if they achieved a deep remission. It was an international multicenter study, so there had been other studies done previously that were single-center studies with our group here at MD Anderson, [and] there was a UK group that also did a similar combination trial with ibrutinib plus venetoclax. There were several sites involved in that, but this was a larger study with a larger number of sites. So I think it clearly confirms that there’s effectiveness to the treatment, or efficacy, as well as demonstrating that there’s safety with the combination.

DocWire News: What were the key takeaways from the study?

Dr. Wierda: The key takeaways from this presentation, earlier analysis for this study, have been previously presented. So the trial has demonstrated that there’s a high proportion of patients who can achieve a deep remission and confirmed undetectable MRD status with fixed duration of 12 cycles of combined ibrutinib plus venetoclax. The importance of this presentation at ASH is for the primary endpoint to be reported, and that is the disease-free survival rate between patients who were randomized, patients who achieved confirmed undetectable MRD status and were assigned to either placebo or ibrutinib single-agent continued therapy.

The primary endpoint showed that there was not a statistically significant difference in one-year disease-free survival between those two arms, placebo versus ibrutinib single-agent, and therefore supporting the rationale and approach for fixed duration combined treatment with reasonable time off treatment for patients who achieved a confirmed undetectable MRD status. It was a frontline study, so all of these patients were previously untreated who were enrolled on this study.

DocWire News: Did any of the study’s findings come as a surprise to you?

Dr. Wierda: They did not come as a surprise; as I mentioned, we had presented previously the undetectable MRD rate, which we expected to be high. With this study, we confirmed the safety of the combination, and there haven’t been any studies similar to this one that have looked at placebo versus continued treatment for patients who had achieved an undetectable MRD status. That is the new data that’s presented with this abstract, the one-year disease-free survival as we have defined it, that being not different between patients who stopped treatment, i.e. received placebo versus continued treatment with ibrutinib single-agent.

DocWire News: What limitations, if any, did the study have?

Dr. Wierda: I don’t think there were any limitations in terms of showing the primary endpoint. I think some of the things that we would be interested additionally in looking at we’re not able to, as robustly, because of the number of patients enrolled in the study. There were 164 patients enrolled in the study. There were two treatment arms that were randomized based on their confirmed MRD status at the end of the 12 cycles of fixed duration. We’d like to be able to look at subgroups and identify high-risk subgroups, etc., and that ability is relatively limited because there are four randomized arms. Patients were stratified in the randomization according to their mutation status. But we’d like to look at other features, such as outcomes for patients with 17p deletion, 11q deletion, and other features that it’s more difficult to do because of the limited number of patients.

There is an additional cohort, which is referred to as the fixed duration cohort. The results that I’ll be presenting are referred to as the MRD cohort, where patients were randomized. For the fixed duration cohort, or [when] there’s a similar number of total patients enrolled, we’ll be able to look a little bit more when we can combine the cohorts and look at outcomes, because there will be a significant number of patients in the whole cohort [in order] to be able to sort of parse out things for subgroups. But with this analysis, it’s a little bit more difficult because of the number of patients enrolled.

DocWire News: It sounds like [there’s] some more ongoing research right now. Are there any future research plans, perhaps for this cohort specifically?

Dr. Wierda: There will be additional data that will be analyzed for the primary endpoint than what the data that’s being presented at ASH 2020 will be the primary endpoint for the study. But certainly additional secondary endpoints will be analyzed both with the data that we have now as well as with continued data that’s collected. Again, the MRD positive or non-confirmed MRD cohort, those patients were randomized to ibrutinib single-agent versus continued combined therapy. And so that cohort will allow us to look at the effects of additional therapy beyond the 12 cycles of combined therapy in that cohort. So we will be certainly collecting additional data and making additional analysis on this study.

DocWire News: Any last information that we haven’t already discussed that you want to share?

Dr. Wierda: I think that the highlight for me is the fact that this supports fixed duration treatment, particularly for patients who achieve an undetectable MRD status, and it also confirms in a large multi-center international study safety and efficacy of combined targeted therapy.