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Frontline CLL Care Continues to Evolve

Danielle Bucco
Published: Monday, May 08, 2017

Steven Coutre, MD

Steven Coutre, MD

The FDA approvals of ibrutinib (Imbruvica) and obinutuzumab (Gazyva) have revolutionized frontline treatment for patients with chronic lymphocytic leukemia (CLL), says Steven Coutre, MD.

Researchers are now focused on further improving frontline outcomes by exploring combination regimens. Additionally, investigators hope that agents approved for later settings, such as venetoclax (Venclexta), will also be successful in the frontline.

In an interview with OncLive, Coutre, professor of Medicine at the Stanford University Medical Center, discusses ongoing efforts to enhance frontline outcomes for patients with CLL.

OncLive: Please discuss the role of ibrutinib and other frontline treatments for CLL? 

Coutre: Things have evolved in recent years and we now have drugs like ibrutinib, which are very different from our traditional chemotherapy or chemoimmunotherapy regimens. They allow the use of an oral therapy that’s well tolerated and effective. That’s an important issue, since most patients with CLL are diagnosed when they’re 70 years old. Most patients don’t need treatment right away making them in their mid-70s when they do need treatment.

Tolerability of therapy is quite important. In comparison to ibrutinib, we have our traditional chemoimmunotherapy. Those regimens, although they are well tolerated, are still harder than taking a pill. They do have toxicities and for people who have a lot of comorbidities, that’s a significant issue.

We also have antibody therapies. For example, obinutuzumab with chlorambucil is also approved in frontline. That’s a little more difficult than taking a pill and it’s not as effective or durable for as long as the oral therapies. 

On the 1 hand, you have a pill you can take, go about your business, and hopefully have little impact on your daily life or quality of life, but right now you do have to take those continuously. We haven’t explored stopping therapy yet. With our more traditional chemoimmunotherapy regimens or immunotherapy, they’re given for a period of time of 6 months or so, which is the tradeoff.

Of course, the other issue that always comes up is cost, the financial impact. 

What are the key considerations for an oncologist when selecting the optimal treatment for a patient with CLL?

We have very well-defined guidelines for when to start therapy, but besides following those, there isn’t an exact algorithm. I always like to think of it as you're looking at each patient as an individual. There might be medical comorbidities that have a significant impact on your decisions, perhaps somebody is too frail and can’t tolerate these chemotherapy regimens. In that case, oral therapy, like the TKIs, might be most appropriate. 

On the flipside, some patients, due to financial constraints, find it better to have a defined course of therapy that might be reimbursed, as opposed to an expensive oral therapy, which might not be fully covered by their insurance. It’s not as simple as just making a medical decision, it’s important to look at the whole picture and have that discussion with your patient to decide what’s best for that individual. 

Are there any emerging agents in frontline CLL trials?

We had idelalisib, another B-cell receptor pathway inhibitor, but because of safety issues, particularly recent ones with infections, it’s not likely to ever get an approval for upfront therapy.

We have venetoclax, which is a BCL-2 inhibitor and an oral therapy. This is approved now but just for relapsed 17p deleted patients, but I am sure that with more trials, a drug like that may make its way into the frontline.

More importantly, where we’re going is combining some of these drugs, to see if we can get a better response and begin to address the issue of stopping therapy. 

An oral, well-tolerated therapy could have added advantages at the time a patient receives therapy. That’s what we’re most interested in. 

Are there specific combination trials that you are interested in? 

Many of them will start with a combination of an antibody, and 1 of these drugs. For example, there are trials with ibrutinib and obinutuzumab as well as venetoclax and obinutuzumab, which the German CLL Study Group has moved ahead quite aggressively.


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