Published on June 24, 2020
Has the Pandemic Changed CLL Treatment Approaches?
How has the coronavirus pandemic impacted treatment for chronic lymphocytic leukemia (CLL), both in the short term and in the long term?
In this segment from a recent CLL Answers Now program, host Andrew Schorr talks to another long-term CLL survivor Nick Bohas about his MRD results from a clinical trial and how he is staying vigilant during the coronavirus pandemic.
They are joined by Dr. Nitin Jain from the University of Texas MD Anderson Cancer Center and Dr. Alexey Danilov from City of Hope, who discuss what MRD means, if certain treatments are being used over other options because of the pandemic, and the importance of FISH and cytogenetic testing.
Although this is a sponsored program, Patient Power maintains editorial control and is solely responsible for the content of this program.
Transcript | Has the Pandemic Changed CLL Treatment Approaches?
Greetings from Southern California, I'm Andrew Schorr with Patient Power. Welcome to this CLL Answers Now program. We're doing these live programs every two weeks now. Thank you so much for joining us. There's always a replay and a transcript, so we hope that we can make a real difference for the CLL community. As many people know, I've been living with chronic lymphocytic leukemia for 24 years. I've been treated twice. You're going to meet some other folks now who are CLL experts, both as physicians and one as a patient. So I want to introduce them. So, joining us from Austin, Texas is my new best friend, Nick Bohas. Nick, thank you so much for joining us.
Glad to be here, Andrew.
Okay. And we should mention that Nick was in the same phase II trial that I was in at MD Anderson back at 1999, 2000. And Nick has had no other treatment since then — I have but Nick has not. We're going to hear more of his story in a minute. Also joining us from MD Anderson is a CLL specialist, Dr. Nitin Jain. Dr. Jain, welcome back to Patient Power.
Thank you, Andrew. Looking forward to the discussion.
Okay. And then also another CLL specialist formerly in Portland, Oregon but now at City of Hope in Los Angeles, Dr. Alexey Danilov. Dr. Danilov, thanks for being with us.
Pleasure to be here. Thank you, Andrew.
Okay. All right, let's start with Nick. Just to be clear, you were treated for CLL beginning in 1999 in the phase II trial of fludarabine (Fludara), cyclophosphamide (Cytoxan) and adding rituximab (Rituxan), right?
And it's worked out miraculously, right?
Wonderful. Well, I was very fortunate.
Okay. But Nick, let's talk about that. Nobody knows what the future brings. So in all these years, you've never known whether you would need treatment again. So how did you think about a plan in your head?
Well, last year, I stopped by MD Anderson and saw Dr. Wierda. And I told him about the outcome and he knew some of my history. And I learned about a concept called MRD, minimal residual disease, which I'm sure everybody here far knows better than I do but I was curious. And they tested me and they said that I have zero MRD. And I asked that again and I clarified that, and zero means zero. I was very ecstatic, very happy. One question I do have is if you have zero MRD, does that mean that you'll never get a relapse or is... What exactly does that mean? How long term of an effect is that?
All right, we're going to discuss that with the doctors in just a minute. I'll just mention my situation. I've never achieved that MRD negative status. It's low but it's not nothing. And as you'll hear in a minute, it's about the best testing they have now. Which means it doesn't show up on the test, but it doesn't mean it's not there. But we'll explore that a little bit more. So we're trying to measure where we are and have a plan. So, in your mind, are you cured or do you keep your eye on the ball as to should you need something, what would it be?
Always keep my eye on the ball, look at the latest advances, look at the latest treatments. I get on my Google as a push form, every time something new on CLL comes up they fund it to me but as a layman’s basis. I'm constantly surprised that the number of new treatments out there. Seems like every week there's another monoclonal antibody that's out there. So I was curious, I haven't seen FCR spoken about in years.
Right. Well, we're going to talk about all that. So, the purpose of this program is with the COVID-19 pandemic as an overlay. And Dr. Danilov is in Los Angeles County and there are high numbers of patients there. Dr. Jain is in Harris County in Houston and there's a growing number there. People are wondering, during this time, short term and long term, how does it affect what our options are for CLL and what to do when? So Nick, you can help me, we're going to go through this. Let's start with Dr. Jain. So Dr. Jain, first of all, just to knock off this MRD, minimal residual disease or measurable residual disease, Nick's zero, I'm not quite that. So does the test mean no CLL no matter what the number is or are we still in fact, a CLL patient?
Yeah, so that's actually a very great question that gets asked by patients all the time. So one thing I would clarify, as Andrew you were mentioning, is that MRD zero or undetectable MRD or MRD not present or MRD negativity, these are different terminologies sometimes we as doctors use. But what that means is that the test we are doing is not able to see it, it doesn't mean that it doesn't exist. And the reason for that is that the most common test we do at least at Anderson is a flow cytometry, which can detect one cancer cell in 10,000 normal cells. So if you have your leukemia cells, one in a million or one in less than that, the test will report a zero because the test cannot see it. But again, it doesn't mean that it's not there. So there are some assays which can look at much deeper level, well, maybe one in a million. But again, even if that is negative, that's not a guarantee that you will never have recurrence of your CLL. So it just means that we have decreased the disease at a level that tests cannot see it but maybe it's present just below that and that's something we don't know. So that's why we don't call it cure, we say it's a deep remission which you have achieved.
Okay. Thanks. And congratulations to you, Nick. It's a deep remission that's been many years. So Dr. Danilov, one of the things we're wondering is, does the pandemic affect decision making on a treatment plan? So what's your view of that now?
Right. So that's certainly a very good question which many patients and physicians struggle with. Because as you know, this pandemic is a new thing and there is very little data or no data on how many of these CLL treatments that we've been using for the past few years perform in this context. And with the rules of social distancing, obviously, one factor that plays a significant role is the number of visits to the clinic or the depth of cytopenias or immune suppression that the treatment can cause. So those are the two factors which go into play when one thinks about treatment for CLL. So the first, of course, is that as we do in CLL, we often do use the watch and wait approach or watch and worry, as many call it, where treatment is not initiated until certain symptoms or blood abnormalities appear. And certainly in my practice, when the pandemic was at its height, I have delayed starting treatment as much as I could.
So we try to make sure that treatment is really necessary, that we qualify all the criteria to start therapy because as you know, at least in the era of chemotherapy, the data is such that early treatment does not improve patient survival. So, delaying treatment is one potential approach to avoid it at the height of the pandemic. And then the second question is treatment choice. And in the current era, the role of chemoimmunotherapy, which would be the most immunosuppressive by far, has decreased because of the advent of new agents such as BCL-2 inhibitor, venetoclax (Venclexta) and BTK inhibitor, ibrutinib (Imbruvica), acalabrutinib (Calquence) are currently approved. And say, if we are not using chemotherapy, the choice between those two agents becomes difficult or complicated rather, complicated, complex, even not in the context of the pandemic. Those are different treatments with different side effects. But overall, what characterizes combinations of venetoclax is necessity for monitoring of tumor lysis syndrome with frequent clinic visits, introduction of an infusion of a CD20 antibody such as obinutuzumab (Gazyva).
So overall, particularly in the first three months, the clinic visits are more frequent. And in conversations with some of my colleagues, I am finding that many of them have been using BTK inhibitors more frequently for frontline therapy of CLL for that reason. Even those folks who have physicians who have previously really favored therapy with venetoclax-obinutuzumab combination for previously untreated CLL, this pandemic has been giving them a pause because of the frequent clinic visits and the complexity and the risk of exposures that patients might have while undergoing this treatment. So yes, the short answer is yes. The pandemic has changed how we think about treatment of CLL but I don't know that it necessarily change it in one direction for all of us.
Okay. Well, let's talk about that. So Dr. Jain, CLL can be really individualized. We have questions that people ask, "Well, what if I have this 17p deletion?" Some people do, a lot of people don't. Do you make decisions just like you did before the pandemic based on some of that or other situations? So when you decide there's an indication for treatment, Dr. Danilov was talking about watch and wait or watch and worry or retreatment if somebody comes out of remission, do you still look at the full range of your armamentarium, if you will, which increasingly includes research you're doing on combinations?
Yeah. I mean, I completely agree with Dr. Danilov in terms of the point he raised about that. I think the chemotherapy itself has declined quite a bit as a management for patients with CLL. We're using less and less of chemotherapy. Obviously, I know you and Mr. Bohas, you got it, you did well but these days, I think maybe 10% or less patients are maybe considered appropriate for chemotherapy in the first-line setting, meaning that patients who have never had treatment, they're going through their first treatment. So majority of the patients, I think these days are using drugs such as ibrutinib, now acalabrutinib, now venetoclax. And our practice also, I think, in terms of the COVID situation also very much mirrors what Dr. Danilov mentioned in terms of maybe less reliance on chemotherapy, which anyways we were doing less reliance on chemotherapy, and maybe doing more drugs which our patients can have less travel back and forth to the campus.
Now to your specific question about deletion 17p, I think that's certainly a very important test. From patient's standpoint, I think this is something you should know about your CLL, whether you have deletion 17p or not. This is something which can be checked by a test called FISH assay. And that can be done in the blood easily, you don't really need a bone marrow to do it. Actually, blood is the [inaudible] way to do it. And also a very similar aspect is what is called TP53 mutation, which is a molecular assay, which again, can be done in the blood. And again, both have a very similar decision tree, if you have either of them what it means is that the chemotherapies are not going to be effective.
So these patients, if you have that really make sure that chemotherapy is not something your doctor or you are entertaining for yourself. And I think, what is ideal treatment for them among the new therapies... Again, new therapies are venetoclax-based therapies or ibrutinib-based therapy or acalabrutinib-based therapy. I think it could be a matter of debate among the CLL experts as well. I think there is some discussion that maybe long term therapy with a BTK inhibitor such as ibrutinib and again, more recently acalabrutinib, may be an appropriate therapy though for some patients venetoclax-based therapy would also be quite appropriate in the first line setting for these deletion 17p patients. So certainly, I think the big take home message I would say is that, do not embark on a chemotherapy strategy if you have deletion 17p or p53 mutation.