At the 65th American Society of Hematology (ASH) Annual Meeting in San Diego, California, Adrian Wiestner, MD, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, presented long-term follow-up data on a phase 2 study of the efficacy, safety, and depth of response of Bruton's tyrosine kinase (BTK) inhibitor ibrutinib therapy for patients with chronic lymphocytic leukemia (CLL). 

Wiestner and study authors noted that these results enhance understanding of the long-term prognosis of patients treated with BTK inhibitors for CLL.

Transcript: 

My name is Adrian Wiestner. I'm a hematologist and investigator at the [National Institutes of Health] (NIH) working on chronic lymphocytic leukemia. I'm here at the ASH meeting 2023 in San Diego. It's been my pleasure to present the long term data from our study with ibrutinib that we initiated in 2012 and have continued to this date. 

We originally enrolled 84 patients with variable risk factors, [such as] patients older than 65 who didn't really tolerate the aggressive regimens used at the time. All patients [had] deletion 17p who responded poorly to chemotherapy. We offered those patients a new treatment approach, and we had very quick enrollment. We had 84 patients over a 2-year period. The response rates have been high. It takes some time to get to complete response, but what's most remarkable with the 10-year follow-up is that we see excellent survival.

So, 3 out of 4 patients with low-risk factors are alive at 10 years, whereas with the high-risk group, it's lower than that. Still, the progression-free survival has also been very rewarding. Patients remain on treatment with successful control of their disease. 

Now, of course, over a long period of time, we also have treatment discontinuations, and most of that has actually been due to progressive disease. We know that with longer time treatment, patients develop mutations that then make ibrutinib less effective. Another group of patients, about 1/3, actually, discontinued for side effects.

What is maybe most remarkable is that the single agent ibrutinib therapy was very effective for patients with the deletion 17p who got this treatment as their first ever line of therapy. It has really improved their survival over this long-term period. What biologically is remarkable is that we see, increasingly, patients achieving what we refer to as undetectable minimal residual disease. We, with very sensitive methods [and] with flow cytometry, do not see any CLL cells left in the blood. That's been a little bit surprising because at the beginning of ibrutinib therapy with the BTK inhibitor therapy, we didn't really expect to achieve such a deep level of remissions. 

That's also really asking a question of, why is that? Is it just because, overall, CLL is a relatively indolent disease? So, if you treat long enough, maybe you can just eradicate all cells? Or, what I would favor is that maybe there is a contribution of the patient's own immune system. So, we're working on addressing that question. Potentially, we have seen that BTK inhibitors do improve immune function, so there could be a control of the immune system against the tumor. I'm really happy to see this good outcome for patients, and it's been very rewarding to have this long-term follow-up.

They also really acknowledge that this study has had variable [principal investigators ] (PIs) over the years [who] led this study, and so it's been a big team effort, [and I] really acknowledge that patients have contributed a lot to it. We draw a lot more blood at NIH. We've asked these patients to give us lymph node biopsies. It's really been a team effort where the patients are truly part of the research.

Source: 

Itsara A, Sun C, Bryer E, et al. Long-Term Outcomes in Chronic Lymphocytic Leukemia Treated with Ibrutinib: 10-Year Follow-up of a Phase 2 Study. Presented at the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 201