Published on June 7, 2016
Two-time cancer survivor and Patient Power host, Andrew Schorr, speaks candidly with Dr. Philip Thompson, CLL specialist at MD Anderson Cancer Center. Together, they explore MRD (minimal residual disease) negativity and how this status impacts long-term disease results. Dr. Thompson discusses consolidation strategies that may positively impact 11q and 17p deletion patients as researchers seek answers for a cure.
Provided by CLL Global Research Foundation, which received support from Acerta Pharma, Gilead Sciences, Inc., Pharmacyclics, Teva Pharmaceutical Industries Ltd and TG Therapeutics, Inc. and the Patient Empowerment Network, which received support from AbbVie Inc. and Genentech Inc. It was produced by Patient Power in partnership with The Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center.
Transcript | What Does It Mean to Achieve MRD-Negative Status?
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Hello and welcome to Patient Power. I'm Andrew Schorr. I'm with Dr. Philip Thomson from MD Anderson Cancer Center in Houston. Thank you for being with us.
Thank you for having me, Andrew. Good morning.
Dr. Thompson, so MRD negativity, minimal residual disease, so I know in my own case, treated many years ago with CLL, knocked it way back, but it's still kind of there, hiding. So I've lived many years with it. So how important is that MRD-negative status?
Well, we know from historical data that if you do achieve MRD-negative status, then you're more likely to have a longer time without disease. I guess it makes intuitive sense, right, the less disease there is the longer it will take to grow back. I guess more recently where it's becoming important is it's kind of a prerequisite for cure, and we do think that there's a proportion of CLL patients we can achieve cure in, And in order to do that, we have to get them MRD negative.
Now, some patients, particularly with newer therapies, will have detectable disease that will be quiescent and stable on therapy for many, many years, and that's raising a new question, which is do you really need to get down to these very, very low levels if you can have someone who is well and has no symptoms and is in a stable state on medications? So the question is kind of becoming more complicated over time.
But I guess most importantly you have to decide what is your goal of therapy, and that may not be the same in each patient. You have to take an individual's circumstances into account.
You know, in many cancers people say, well, I want to beat the cancer, I want to fight it, I want to hit it hard. In this condition sometimes in some patients we're talking about hitting it back to a very low level where you go on with your life, and, quite frankly, that's the way it's been for me. Still have it.
But I've been living my life for many years, might need treatment again. So somebody says, well, gee, am I MRD negative, do we need another therapy right now? And I'm sure you have conversations with people who are stressed. What do you tell them?
Well, I mean, sometimes we can do harm by giving more therapy. So when we first started doing MRD testing routinely after initial therapy, so say we gave chemoimmunotherapy with FCR or something similar, there were a number of attempts made subsequently to say, well, okay, those patients who still have MRD after treatment are likely to relapse earlier. So we're going to come in and give another therapy, a different therapy straightaway in an attempt to get MRD negativity.
And so there was one particular clinical trial where patients were given alemtuzumab, Campath, and—straight after FCR, and it achieved MRD negativity in about half the patients. But it was prohibitively toxic, and there were a lot of patients who got serious infections, life-threatening infections, and there were deaths due to those infections, which kind of negated any benefit from that.
We probably have some newer tools that are going to enable us to re-examine this question. For example, some drugs like venetoclax (Venclexta) or ABT-199, which is very effective on its own at achieving MRD negativity and is minimally toxic, we may be able to use that as a drug to try and achieve MRD negativity with minimal toxicity. But I would say if you can design what we call a consolidation strategy which has minimal toxicity, then it's something that could be examined, but it's not necessary in all patients.
Right. Right. And I've been living well. So for patients who get there, okay, do you feel this "cure" word is real?
For certain subgroup of patients, yes. So our data suggests that if you have favorable prognostic features before treatment, and by that I mean you have a mutated immunoglobulin heavy-chain gene and you have an absence of high-risk cytogenetic features, so you don't have an 11q deletion, you don't have a 17p deletion. And probably you don't have high-risk molecular features like a mutation in the TP53 gene, then if you achieve MRD negativity after treatment, our data suggest that about 80 percent of those patients then go on to not relapse when you look at them for 10 or 15 years, which is pretty exciting, but it's a very selected group.
Now, we can get MRD negativity with FCR in patients who have higher risk features, like say they are unmutated and have an 11q deletion. Many of those patients do achieve MRD negativity, but they all relapse. Now, that says to me that probably those patients have a small amount of disease just below the level of detection of the test. And maybe if we had a more sensitive test, we would be able to find it. But because of that knowledge that even when we achieve MRD negativity in those patients they all relapse, we're trying to move away from chemoimmunotherapy in those patients and develop different, less toxic strategies for them.
Okay. So just to sum up. There are some people where what you know about them they have a good chance of actually being cured, and with newer medicines now we're trying to see if that "cure" word can apply to more people.
Okay. Well, you're a younger physician, and we hope in your career, and maybe early in your career, we can see this happen. Thank you so much for being with us.
You're welcome. Thanks for having me.
Dr. Phil Thompson from MD Anderson Cancer Center.
I'm Andrew Schorr. Remember, knowledge can be the best medicine of all.