Progression-Free Survival Among Patients With Chronic Lymphocytic Leukemia Treated With Ibrutinib

Kerry Rogers, MD, Division of Hematology, The Ohio State University, Columbus, OH, discusses a retrospective cohort study looking at depth of response and progression-free survival outcomes among patients with chronic lymphocytic leukemia treated with ibrutinib.

Transcript

Hi, I'm Kerry Rogers. I'm an associate professor in the Division of Hematology at the Ohio State University, and I'm really happy today to tell you about some work that was led by my colleague, Dr Audrey Sigmund, looking at depth of response with ibrutinib, and outcome in terms of progression-free survival. And this is a retrospective cohort study, but I think really gets at something quite important that we all kind of wonder about, these continuously-dosed, targeted agents, particularly drugs like BTK inhibitors, like ibrutinib, where you don't see really deep remissions. There's always questions about what predicts a better progression-free survival. Does it matter if you eliminate lymphocytosis? Does it matter if lymph nodes decreased? Does achieving a complete remission, and at what interval, really help predict progression-free survival, especially knowing that patients stay on the drug? In terms of achieving deep remissions or undetectable residual disease, I think that matters a lot for the conversation about fixed duration therapies or when to stop treatment, but it's still kind of a question if we're going to continue BTK inhibitors, how important is achieving a complete remission or a deeper response?

And previously, our group, I believe the effort was led by Dr Woyach, had shown that prolonged lymphocytosis was not a negative predictive factor of progression-free survival, and actually seemed that patients with prolonged lymphocytosis or elevated ALC with BTK inhibitors had an improved progression-free survival. So I think it's important to kind of look at the depth of response angle, too.

So this was a retrospective cohort study that included 237 patients that were treated at our institution with ibrutinib, mostly as a single agent, but some in combination with other agents, just looking at just response, and then also a couple other disease features associated with PFS.

The response achieved earlier into treatment, at around 12 months, did not actually predict progression-free survival. Very few of patients, so less than 5%, achieved a complete remission, but that didn't predict progression-free survival, which is very different than what we see with treatments like chemoimmunotherapies. And I think does argue that these continuously dosed drugs that are targeted, that interfere with disease biology, are really different.

However, multiple enlarged lymph nodes at that duration of treatment did actually have an inferior progression-free survival. So while we had previously shown lymphocytosis didn't decrease PFS, or that CR wasn't important in this analysis, multiple enlarged lymph nodes were actually shown to shorten the progression-free survival. So that may be something that could be used as a clinical tool to predict who might progress on BTK inhibitor continuous monotherapy.

There was a uni-variable and a multivariable analysis of factors that were associated with PFS, including age, and MIC abnormalities, and then unmutated IgHV status, showing that those unmutated IgHV or MIC abnormality were associated with a lesser progression-free survival.

So I think those were kind of interesting findings, but this one about lymph nodes and multiple enlarged lymph nodes at 12 months being associated with a shorter PFS is something that might actually be helpful in clinical practice quite a bit when taking care of patients, and also might be useful going forward, not only for picking out who might have a shorter PFS, but really supports that maybe strategies that decrease lymph node size combined with BTK inhibitors might be a good one moving forward.

And I think it's just always nice to have these kind of retrospective analyses to look at a group of patients, many of whom were not in clinical trials, although, obviously, some would have been included that were, just to kind of look at other ways of looking at this kind of information to inform both research, but clinical practice. So I enjoyed participating in this project led by Dr Sigmund in my group, and would like to thank all of you for your attention today.