CLL Treatment Advances: What Do You Need to Know?

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CLL Treatment Advances: What Do You Need to Know? from Patient Empowerment Network on Vimeo. 

Dr. Matthew Davids reviews promising chronic lymphocytic leukemia (CLL) research and shares online resources for patients to stay informed as treatments develop.

Dr. Matthew Davids is the Associate Director of the CLL Center at Dana-Farber Cancer Institute. More about this expert.

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Transcript:

Dr. Matthew Davids

So, this remains a very exciting time for CLL research. The last several years have witnessed the development of a number of these novel agent-based approaches, these oral drugs that target the different pathways inside the CLL cell that the cell survives with.

And so, we’ve really kind of reached the end of the beginning, as I call it, because the first goal, of course, was developing each one of these novel agent drugs on its own. We had to show first that they were safe and figure out what the dose was for patients, and then figure out that they’re effective on their own. And we’ve kind of checked those boxes at this point and reached a point where we have now several different novel agents that are FDA approved already for CLL patients.

And so, I think the big research challenge now going forward is kind of twofold. One is identifying the best combinations of these drugs to put together. And No. 2, identifying which patients will benefit most from which specific combinations.

And so, there’s a number of different clinical trials going on right now looking at these questions.

And just kind of highlighting some of them, one of them is the study of venetoclax with obinutuzumab that I mentioned before. We just had a pretty early readout from this study. But I think it’s gonna be very important to see how patients do over time after they finish the one year of therapy, and both for this study as well as another study called MURANO, which looked at the patients who had already had prior chemotherapy-based regimens and then received venetoclax, in this case with rituximab.

In both cases, when there’s time-limited therapy, I think a key research question is gonna be, when those patients do have progression of the CLL – hopefully years later – do they respond again to that same treatment? Can you use venetoclax again? And do the patients respond nicely? And if they do, then that could be a very nice intermittent treatment strategy to allow patients to be off therapy for a period of time, and then only to receive additional treatment when they need it.

I think another important and exciting area is the combination approaches. And I’ve talked about both ibrutinib and venetoclax as probably two of our most promising new drugs. And so, there are now a number of different studies exploring the combination of ibrutinib plus venetoclax given at the same time. And some of the initial data that’s been published looks very promising. This is a very well tolerated and highly effective combination in the initial studies. It’s all oral, which is nice. So, it’s just pills without the need for any infusions. And again, it’s designed to, hopefully, be a time-limited regimen, and patients hopefully will have a nice durable response after an initial treatment with these two drugs.

There are certainly a number of other drugs that are very promising as well. There’s a whole class that we haven’t talked about yet called PI3 kinase inhibitor drugs. We have two such drugs currently approved now for CLL patients, idelalisib and duvelisib. These drugs also are very effective for treating CLL but tend to have more side effects when they’re given as the first therapy. So, most patients will start with a different therapy. But then the PI3 kinase drugs can be a great option for patients who are in the relapse setting after they’ve had prior treatments.

And there’s another one in development called umbralisib, which also looks very promising and seems to perhaps be even the safest of these PI3 kinase inhibitor drugs. And that’s not yet FDA approved. But we anticipate it’s likely gonna get an approval relatively soon.

And so, combining these new PI3 kinase drugs also with venetoclax is an area of research interest, and a number of other combinations. As you can imagine, the longer the list grows of drugs, the more different combinations we can explore. And we’re trying to use the science from the laboratory to try to determine ahead of time what we think are the most promising strategies because we can’t do clinical trials of every single combination. But those are some of the sort of novel agent studies that I’m excited about right now.

I think the other area that could prove to be very helpful for our CLL patients is CAR T-cell therapy, which stands for chimeric antigen receptor T-cells. CAR T-cell therapy is a way to harness the body’s own immune system to fight cancer.

So, to do this, we would take cells out from a patient. And these are T lymphocyte cells. So, not the CLL cells, but a normal immune cell called a T lymphocyte. And then the cells get educated outside the body to recognize CLL cells more effectively. And they’re grown up and expanded and then reinfused into a patient, where they can go around and kill CLL cells. This can be a very effective treatment and can lead to complete remissions with durability.

And this approach is now in clinical trials. There are some risks to CAR T-cell based therapy. Something called cytokine release syndrome, where patients can get very sick, almost like they have a severe infection, but they don’t have an infection. There’s some neurologic risks to this as well that can be quite scary if they happen but in almost all cases are reversible. So, I think that this is an interesting area of research right now. It’s certainly not yet approved by the FDA for CLL. But we hope that, over time, as the CAR T-cell therapy becomes more effective and has fewer side effects, that eventually it will become a therapy option for patients who have had prior treatments for their CLL.

So, I think despite the fact that we’ve made a lot of advances in the last few years, we still have a lot of work to do in the research area to try to improve our treatments even further for our CLL patients.

So, in terms of how patients can stay informed about all these developments, it frankly is quite challenging, even for us in the field, to keep up with all of this. But there are some resources that can help. The first thing I would say is that the research tends to come along in fits and spurts, and one of the fits is generally the big research meetings where we all gather together to present our new data.

And probably the biggest highlight of the year is the ASH meeting, American Society of Hematology, which is usually in early December. That’s a good time to start looking on the internet for news about CLL, latest treatments, those sorts of things. Often, it’s kind of early December where we first hear about these breaking stories.

Another meeting that’s become big over the last few years is the European Hematology Association, which usually takes place in mid-June. And that’s, again, another time when we often see new data coming about. And one area where I would say this could be very helpful – or one website that I think is helpful – is the CLL Society website. This is led by Brian Koffman, who himself is a CLL patient.

And he kind of collates a lot of the information from these meetings and puts them in one place on his website. He’ll often interview CLL specialists to get their opinion about some of the newest developments. And so, I think Brian’s webpage, CLLSociety.org, can really be a great resource for getting up to date on the latest data.

There certainly are other websites out there now as well which are helpful. For example, another one that I’m working with closely is called VJHemOnc. And VJHemOnc comes to these big meetings, again, interviews a lot of the experts on their takes on the new data.

And I find that this platform in particular, the video-based platform, can be very engaging. It really forces us, as the investigators, to kind of hone down on what the most important key points are and give little snippets about that. And I would think that would be easier for our patients, in many cases, to digest, compared to some of the original papers themselves, which can be quite dense.

So, those would be my major resources that I’d recommend for CLL patients who are looking for additional information on the latest research.

You’re Not a Guinea Pig: Understanding Clinical Trial Participation

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You’re Not a Guinea Pig: Understanding Clinical Trial Participation from Patient Empowerment Network on Vimeo. 

“Will I be a guinea pig if I participate in a clinical trial?” CLL expert Dr. Brian Hill explains the clinical trial process and addresses common patient fears and misconceptions.

Dr. Brian Hill is the Director of the Lymphoid Malignancies Program at Cleveland Clinic. More about this expert.

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Transcript:

Dr. Brian Hill:

So, one of the first questions many people ask about being a clinical trial participant is, “Am I a guinea pig?” And what I would say is we’re always practicing medicine. Anything we do, we’re practicing.

But we are always trying to get better whether it’s formally on a trial or not. In terms of side effects of treatment, no matter what – if we have the treatment available, any medication can potentially cause side effects. And it’s very difficult to predict. So, even if you are not on a clinical trial, you could be treated with a standard therapy and potentially have problems or difficulty with it. In terms of clinical trials, it depends where in the sort of journey you are in. If you have never been treated before and now you need to be treated, there are trials that are appropriate for people who are at their first line of treatment.

And this is not typically where we are experimenting with new drugs. So, this is typically where we have established treatments or just sort of trying to compare which one is better. Sometimes these are randomized.

So, there’s a flip of a coin, and you can be assigned to one or another. And I understand why many patients may not want to have their treatment determined by chance. But I would keep in mind that usually if this is being done, it’s been vetted through not just the institution where they are being treated, but often times through review boards throughout the country who basically say, “We think it’s okay to have a flip of a coin decision here because if we have a great treatment which is A and a great treatment which is B and we really don’t know if A or B is better, it’s okay to sort of have a randomization where you may get A or B.”

Sometimes A is the standard and B is likely to be better, but we don’t really know that B is better. And the only way to get the second option would be to be on the clinical trial. So, in that case if you are enrolled, the “worst” option would be the standard.

But it may give you the option of being even better than the standard. And again, if we knew that the second option was better then it wouldn’t be a clinical trial, it would be our standard.  This is sort of how we make progress. And it requires a buy in from the medical community and physicians, but also, it’s important that patients feel comfortable with it. So, that’s kind of for front line treatment. In terms of subsequent therapies, again there are a lot of very good standard treatments available.

And sometimes there are new drugs that are being developed. If the new drug has never been given before to a human, that’s called a Phase One trial. And typically, those are given or offered to people who have had many other lines of therapy and may not have other good options. But sometimes we know that the new drug has been given to people, it’s safe.

The side effect profile is already known even if it hasn’t been given to large numbers of people. And in those cases that would be something around something often called a Phase Two trial where we know it’s safe, but we’d love to see how well it works. And that’s an option for patients as well.

Right. So, outside of talking with your hematologist/oncologist or CLL specialist, there are many other resources for getting information about CLL. The Lymphoma Research Foundation, The Leukemia Lymphoma Society and the CLL Society are all great organizations that have useful websites.

They have 1-800 numbers you can call into. Many of these groups have – I know the CLL Society has a support group in many cities that’s held on a regular basis. And often times there are patient meetings organized through LLS or LRF, the two groups that I mentioned, that allow patients to come and learn from each other and also ask questions of specialists who may be speaking at those events.

How Can Patients Learn About Developing CLL Research?

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How Can Patients Learn About Developing CLL Research? from Patient Empowerment Network on Vimeo. 

Dr. Danielle Brander explains why it’s important for chronic lymphocytic leukemia (CLL) patients to stay up-to-date on developing research and treatment news. Dr. Brander also shares resources for learning more about clinical studies.

Dr. Danielle Brander is Director of the CLL and Lymphoma Clinical Research Program at Duke Cancer Institute. Learn more about Dr. Brander here.

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Transcript:

Dr. Brander:

I think it’s very important that patients and their caregivers stay informed and advised of opportunities to participate in ongoing research. I think there’s a misconception that with all the favorable progress in treatment options available for CLL, that there’s no longer the need for clinical research participation.

Though, there are a lot of novel options available for CLL, there’s still a lot of ways that we can improve care for patients. That is, there are trials with the next-generation inhibitors or for patients traditionally with harder to treat CLL or may become resistant to the novel agents, there’s a lot of trials looking into how do you combine the novel agents to give patients the best options. And then a lot of the research, too, are not just in the treatments.

But as our science advances into looking at other markers of the CLL cells, or what we call the depth of response, how much CLL you kill with the treatments and how low of a level we can get in terms of detection. This may result in a situation where patients have the opportunity to receive novel treatments, have a really good response, and then potentially stop the treatments and be followed off of therapies, so have the benefit of novel treatment but not with having to go on an ongoing drug forever and ever.

When I talk to a patient about opportunities for clinical trials, I’m really focused on the patient in front of me. That is, I wouldn’t offer or talk about a trial if I didn’t think it potentially could benefit the patient in front of me.

And again, though we’ve had a lot of advances in treatment options, there are certainly a lot of ways that we can engage and hopefully help patients moving forward. There’s been recent studies across all cancers showing that unfortunately a very low percent of patients are offered and enrolled and participating in clinical research studies, and I think it’s really important that patients know there’s a lot of opportunities out there that potentially could benefit them.

The different ways to be advised and informed, again, are some of the resources online educationally for CLL and lymphoma that often post about different sites for clinical trials. There’s a clinical trials.gov web site that all sites in the United States that are enrolling trials with patients have to log clinical trials, and though that has to be updated, it often can be a good beginning site.

But in the end, hopefully the best resource is your treatment team, your oncologist, and your other team that can help point you to what trials might be eligible for you, either at the location where you are or close by.

The last part I’ll point out is though we focus a lot on the treatment clinical trials, in CLL, where patients don’t always need treatment right away or may have treatment and have a response and then have a long period of time afterward, is that many centers are helping to engage patients in research that is not necessarily done during the time of their treatment. Again, to try to understand why some patients have a longer course until they require treatment, or why they might have responded differently, or other ways we can improve their care.