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ASH 2018 – Tools for Staying Up-to-Date on CLL Research

CLL patient advocate, Lee Swanson, interviews Dr. Anthony Mato, Director of the CLL Program at Memorial Sloan Kettering Cancer Center about the exciting news for CLL patients at the ASH 2018 meeting.


Transcript: 

Lee Swanson:

Hello.  I’m Lee Swanson at the American Society of Hematology conference in San Diego joined right now by Dr. Anthony Mato from Memorial Sloan‑Kettering in New York.  And, Doctor, CLL, what’s come out now at this conference about CLL that patients want to know about?

Dr. Mato:

This has been a very exciting ASH meeting for patients with CLL.  There’s been a couple of big themes, but probably the largest is the comparisons of novel agents to chemoimmunotherapy combinations.  We saw two presentations looking at ibrutinib and rituximab as compared to the chemo combo FCR, which is a standard of care for patients who are young and fit, and we also saw a comparison of ibrutinib with or without rituximab, the antibody, compared to bendamustine Rituxan.

The overlying theme of the two presentations is that the patients who received ibrutinib tended to do better, certainly in terms of progression‑free survival and even in terms of overall survival with regards to the FCR comparison.  So a big theme is that there are fewer and fewer patients who are the right candidates for chemoimmunotherapy, and it appears that BTK inhibitors, at least as of this moment, will be the standard of care frontline for patients with CLL.

Dr. Mato:

So the good news and the bad news:  You don’t have to do chemotherapy.  On the other hand, chemotherapy is a defined six‑, seven‑month regimen.  Does this mean you’re taking a pill forever?

Dr. Mato:

Based on the current way that ibrutinib has been studied and labeled that means you’re on a long‑term‑‑it’s a long‑term commitment to ibrutinib.  There have been updates at the meeting of ibrutinib‑based and venetoclax‑based combination therapies where there is the hope that giving ibrutinib with a partner, for example, or venetoclax with a partner will allow us to treat to a fixed duration and then stop for patients, and that duration would either be based on some predetermined time point or on depth of response based on response criteria or minimal residual disease criteria.

So right now it’s a long‑term commitment, especially frontline.  In the long‑term I think we’re headed toward the direction where we can define which patients may stop sooner and then be retreated.

Lee Swanson:

If you stop, can you be retreated with the same?

Dr. Mato:

That’s a great question.  There’s not a lot of information about that, but there’s no reason biologically to think that that wouldn’t be a problem.  Specifically, if you stop in the setting of responding disease it’s not likely you’ve required resistance to that drug, and so retreatment should be a reasonable strategy.  We’re at Memorial Sloan Kettering now designing many trials that will try to answer those questions and allow us to stop either monotherapies by themselves or combinations to treat to a depth of response and then stop, so that’s something we’re really interested in.

Lee Swanson:

So if a patient gets a diagnosis now from‑‑sometimes from a primary care physician, of CLL what’s the conversation they should have?

Dr. Mato:

From the primary care physician?  Well, I think the primaries are great at identifying an elevated white blood cell count and the signs and symptoms of CLL even making the diagnosis.  Flow cytometry is readily available now to anyone who wants to order it.  I think the conversation with a primary care physician should be who should that patient see as a CLL expert to help guide the observation period which is important, as many patients are not treated initially, and also to help them to be informed as to how the field is changing.  Because the progress is so rapid you really need to have someone who is focused in on this area to help guide that particular management strategy long term.

Lee Swanson:

It’s important to get to a specialist, at least get a communication with a specialist.

Dr. Mato:

Exactly.  And of course the local oncologist and the internist are very important in terms of patient management, but ultimately there could be somebody who could help drive that‑‑some of the more important decisions based on the newest standards.

Lee Swanson:

So all of these things coming out, how does a patient keep up on what’s going on?

Dr. Mato:

That’s a really great and difficult question to answer because there’s so many different sources of information, some more reputable than others on advances in the field.  I think that probably the best source is having a physician, a trusted provider who is up to date, who can help interpret some of the more complicated findings from the research studies.  But in addition there are patient organizations and professional societies who are reputable, who provide up‑to‑date, very reasonable recommendations, either through their websites or through the literature that they provide for patients.

I think trying to avoid just general Google searches for advice on management of CLL is a good idea to not do.  I find that oftentimes things that get posted online can be just one‑off examples where somebody’s either extremely happy with care or very unhappy with an event, and it may not necessarily be representative for all patients.  So I would say professional societies, CLL focus, patient organizations, and then of course having a care team that’s very focused and very specialized in the area so that they can interpret what can be complicated.

Lee Swanson:

Okay.  Thank you very much, Doctor.  Appreciate your time.

Dr. Mato:

Thank you very much.  Yep.

Lee Swanson:

This is Lee Swanson.  I’m at the American Society of Hematology conference in San Diego.

ASH 2018 – Latest News and Research in CLL

CLL patient advocate, Lee Swanson, interviews Dr. Kerry Rogers, Assistant Professor, Department of Hematology The Ohio State University Medical Center, about exciting CLL news and research from the ASH 2018 Conference.


Transcript:

Lee Swanson:

Hello.  I’m Lee Swanson, and this is the American Society of Hematology conference in San Diego, and I’m happy to be joined today by Dr. Kerry Rogers from the Ohio State University Medical Center.  And you are a CLL specialist.  What at this conference has excited you that patients should know about?

Dr. Rogers:

I think there’s a couple really exciting things at this conference that will be very important for patients.  Probably the most exciting thing, in my opinion, hasn’t been presented yet but is being presented later today by one of my colleagues.  And then there’s a late‑breaking abstract that will be Tuesday that’s really exciting.

And these are studies comparing ibrutinib‑based regimens to a chemoimmunotherapy regimen.  So that’s a comparison of a pill targeted agent with a course of chemotherapy with an antibody, and the exciting thing here is that taking the pill oral targeted agent seems to be doing better for patients in a really important way which is how long people are living without their CLL progressing or returning.

So this is the first time we’ve had a large‑scale comparison of a chemotherapy to a chemotherapy‑free treatment.  And just to go into a little bit more detail, if that’s okay, there is a study through a cooperative group called the Alliance, and that is a group that does very large studies at multiple centers in the United States that compared BR to ibrutinib to ibrutinib and rituximab.  They found that there is no difference in something called progress‑free survival, which is how long people are alive without their CLL returning or causing problems between both the ibrutinib arms, but a substantial improvement between the ibrutinib treatment and the chemotherapy treatment, which is bendamustine and rituximab.

So this means that ibrutinib regimens are out performing chemoimmunotherapy, and that was in people 65 and older.  And I think that’s very exciting because it’s showing that we can treat CLL more effectively in this way than with BR which is the standard chemoimmunotherapy, and these are all people who are taking their very first treatment for CLL.

There’s a similar study in younger patients comparing FCR to an ibrutinib‑based regimen with very similar results.

Lee Swanson:

Really.  So are we looking at a day when that will become standard of care?

Dr. Rogers:

I firmly believe that‑‑of course, each individual person needs to select a treatment that’s best for them, but I think it is a standard of care now to do an ibrutinib‑based treatment rather than chemoimmunotherapy for the majority of people taking a first treatment.

Now, there are select individual patients who will have a very prolonged benefit from FCR, people who have an IGHV mutated status, so it’s a particular test that shows that these people have just a very nice benefit from FCR, but other than that group it is now the standard to do these ibrutinib‑based treatments.  And I think both these studies are what is showing us that this is a standard.  It’s definitely the most important thing for CLL I think at this meeting.

Just to plug how important this is, my colleague, Dr. (?) Wyak, who’s presenting the Alliance study, is doing so at the plenary session, and that’s the talk where they pick the very, very best kind of studies or data from the entire meeting, so not just CLL but noncancer blood disorders, other blood cancers.  So this is really a very important thing for people with CLL.

Lee Swanson:

Show how does a patient go about talking to their doctor about these emerging…

Dr. Rogers:

Yeah, so I think it’s really important to be able to ask your doctor anything, and this is something that people should talk with their doctor about.  Both these studies were in people taking a first treatment for CLL, but that doesn’t mean that this type of finding isn’t important to other people.  And I think if you’re considering a first treatment for CLL and need a first treatment for CLL I think sitting down with your doctor saying, you know, finding out what they recommend but then also saying, you know, how do you feel about these chemotherapy treatments versus ibrutinib‑type treatments and seeing what they have to say.

And of course I think it’s very fair since this data is going to be presented at this meeting to ask your doctor about these large studies.  These are the type of really big studies that should be understood by the majority of oncologists.  So I think it’s okay to ask them specifically, just, hey, what do you think about the studies comparing chemotherapy to ibrutinib?  How does that apply to me as a person?

Lee Swanson:

So chemotherapy of course is a refined, six sessions or generally.  Ibrutinib, are they then looking at a prolonged use of ibrutinib?

Dr. Rogers:

Yes.  So both these studies, the ibrutinib was continued indefinitely which is the way it’s supposed to be prescribed in the United States, versus chemotherapy, which is a combination of chemotherapy and then antibody for about six months of treatment, so that is an important consideration.

Also at this meeting there’s data about combination regimens that don’t include chemotherapy that are a fixed or limited treatment course, so I think that’s also very exciting.  Those studies are now not very far into follow‑up, so people have only finished those treatments for a year or so.  I think that when we look at these chemotherapy‑free combination treatments we’re really going to need to see how long people do really well after they finished treatment to know what the true benefit is, but that’s also very exciting to see that happening.  It might allow people to avoid chemotherapy, stop treatments and get very good remissions that last years and years.  We just haven’t had them long enough to know the years and years yet like with some of the chemotherapies.

Lee Swanson:

Of course.  So one of the‑‑one of the things about CLL is that it finds a way around treatment often.  They clone cells or what‑have‑you that then, you know, so you’re looking then at second‑ or third‑generation medications sometimes.

Dr. Rogers:

Yes, that’s true.

Lee Swanson:

So that’s going to be a continuing challenge.

Dr. Rogers:

Yes.  I think that is a continuing challenge, and when we see more of these people taking these oral targeted agents, these pill treatments that aren’t chemotherapy that are taken for an extended period of time we’re going to see more people where those treatments stop working or develop resistance, and just because we’ve now shown it’s superior to chemotherapy‑based treatments as a first line doesn’t mean that these are perfect.  So we are still working very hard on what to do after you take something like an oral targeted agent for first treatment or even a second treatment or a third treatment.  There’s a lot of research at this meeting being presented in that area too.

We’ve shown venetoclax works well after ibrutinib, but we still are trying to get a handle on has works well after venetoclax.  There’s some kind of laboratory‑based data around venetoclax resistance being shown at this meeting, and I think that’s going to be important too because that’s what helps us build better treatments for those people is to really take a deep look at what’s happening on a cellular level in the leukemia.

The thing I actually saw this morning that I thought was very exciting for people who might have developed resistance to one or more targeted agents is actually CAR‑T therapy.  I think that the more I’ve seen data coming out with that the better it’s getting, the better we are getting at giving that to people.  And while that is definitely not therapy right now for the majority of CLL patients there are definitely some people that benefit from that type of treatment that have participated in research studies with it.  And I think that’s something that’s going to advance and fill some of the need for what we’re going to ideally offer people who have had their CLL come back on these targeted therapies.

Lee Swanson:

So CAR‑T, it’s worked very well for some people.  It’s worked not at all for other people.  Is there a way to be able to target who’s who?

Dr. Rogers:

You know, I really hope so.  Right now I don’t know that we’ve come up with a firm to target who’s going to benefit the most and who’s not going to benefit, but I do think the more experience we get with that the more we’re going to learn about not only who will benefit but also how to make it so more people benefit.  So going in, instead of saying X many people benefit, have a higher percentage of people that undertake it do well with it and to have the side effects of it reduced.  You know, that’s not a fun and easy treatment, so I think the continued work to reduce the side effects and also get it to work for more people is going to be really important.

Lee Swanson:

Well, thank you very much for your time.  We really appreciate it, and it’s very good to talk to you.  Thank you.

Dr. Rogers:

You’re very welcome.

Lee Swanson:

I’m Lee Swanson at the ASH conference in San Diego.

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