Promising Developments in Chronic Lymphocytic Leukemia Treatment

Talal Hilal, MD, Mayo Clinic Comprehensive Cancer Center, Phoenix, Arizona, shares expert insight into promising novel therapies in chronic lymphocytic leukemia (CLL) treatment, highlighting an increasing focus on utilizing measurable residual disease (MRD) as an end point.

“There's been a lot of interest in MRD as an end point. A lot of trials that have been designed in the last 3 to 4 years, as well as ones that are being designed now, are looking at MRD as a prominent end point in the study design,” explained Dr Hilal.

Transcript:

My name is Talal Hilal. I'm a hematologist at [the] Mayo Clinic in Arizona. I treat patients with (chronic lymphocytic leukemia) CLL and lymphoma. I [also] do bone marrow transplant[s] and (chimeric antigen receptor) CAR-T therapy.

There's been a lot of interest in MRD as an end point. A lot of trials that have been designed in the last 3 to 4 years, as well as ones that are being designed now, are looking at MRD as a prominent end point in the study design. There's a lot more MRD-guided approaches happening now in trials. Some of them are treating patients until achievement of MRD and looking at differences and outcomes.

We are seeing a lot more testing of MRD as an end point in clinical practice. It's still early to say whether this has to happen for all patients. And, you know, there's still a lot of questions about the modality of testing, whether by flow [cytometry], by (next-generation sequencing) NGS, [and] blood versus bone marrow.

Some of the exciting trials coming down the line include the MAJIC study, which is testing acalabrutinib-venetoclax versus obinutuzumab-venetoclax; sort of 2 doublet time-limited approaches. There's also—within the design of the study—further treatment based on MRD status. Patients who have MRD at the end of 1 year will go on to receive a second year of venetoclax. We're going to know more about outcomes in patients who are treated based on MRD status and we're going to know more about the utility of the targeted agent doublet.

At this point in time, ibrutinib venetoclax is not approved as a targeted agent doublet in CLL in the [United States]. Some of these studies coming down the line are going to be important to delineate that doublet approach. Will it be just as good as what we've been using now, which is [venetoclax-obinutuzumab], or are we looking at something a little bit better? MRD may be 1 end point, but [progression-free survival] PFS is still going to be important. And if we could even get overall survival here, it would be important. The risks and benefits of these 2 doublet approaches are going to be very important to look at as well. Those are some of the topics that I think are going to be highlighted in upcoming meetings with regards to CLL.

The other thing that I would mention is sort of another class of agents that we're exploring. We have a trial here for this class of agents, which is (Bruton tyrosine kinase) BTK degraders. Right now, we've been using covalent BTK inhibitors in the frontline setting, non-covalent BTK inhibitors in the relapsed setting. Patients who maybe relapse after both of those lines of treatment seem to have responses to BTK degraders, which is another mechanism of degrading BTK and overcoming some of the resistance mechanism.

I think we’re going to see a new class of agents coming down the pike. There [are] several pharmaceutical companies exploring BTK degraders, so it's not a single company here. I think it may be the next thing that we would be prescribing to patients, after BTK and BCL2 inhibitors.