Published on May 17, 2018
Chronic lymphocytic leukemia (CLL) patients on the watch-and-wait treatment strategy may feel uneasy and anxious knowing they have cancer and are not receiving immediate treatment. What is the rationale behind this treatment strategy? Is there a benefit to waiting? CLL expert Dr. Thomas Kipps from the University of California San Diego Medical Center, discusses the latest research from clinical trials on patient outcomes from early intervention and why your healthcare team may choose the watch-and-wait approach instead. Watch now to find out more.
Transcript | Understanding CLL Treatment Strategies: Why Watch and Wait When There Are Effective Therapies?
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Hello from Niagara Falls, Ontario, in Canada. I'm Andrew Schorr. This is my doctor and famous CLL expert, Dr. Tom Kipps from the UC San Diego Moores Cancer Center, a speaker here. Thank you so much for being with us.
Thank you very much, Andrew. It's very nice to be here.
So first of all, here we are where I was originally treated like 18 years ago and had waited four years for treatment, and the thinking was watch and wait. And now you have so many more options, so I'm sure people ask you, and I'll ask you now, why wait when you have effective therapies? We have this feeling that the cancer is building in our body.
Well, that's a very good question. I know that it's sometimes a source of anxiety, because we oftentimes hear that early diagnosis means potential for cure for cancer. It's never been the case for CLL, because our agents have not really been able to effect the type of response that has then allowed us to make assurances that we can cure the disease outright. And also I think that we can't cut it out, so basically we have to have systemic therapies that hopefully get the disease down to a level that allows the patient to live without any complications or side effects.
The problem really has been, quite frankly, that our therapies in the past have certainly had some problems. And in earlier studies, we sort of got our hands burned by actually advocating that patients may be treated earlier in the course of their disease, and what happened in those studies was that we were shocked to find that patient actually lived less long. They actually had a poorer survival with therapy than if they were just left alone by themselves.
And I think this has created some caution that even though we have great new therapies and even though we are seeing great responses, are we going to be repeating the same mistake by advocating therapy for patients when in point of fact they may do well for years and years without requiring such therapy?
I mentioned during the talk that I remember a patient who was really distraught about having CLL and wanted to go for a cure shortly after diagnosis and had her brother's cells harvested for transplant at the Hutch, and prior to going for transplant she came and saw us. And we did some studies and said, hold the phone. We should observe this for a while, and we continued to observe her for 20 years. And I was actually shocked. She was one of the few cases over the years that actually had spontaneous regression in her leukemia.
Now, I guess if we treated her, we can accept the congratulations. But on the other hand, there are still factors we don't know, namely, what governs the biology of the tumor, what governs the host-tumor interactions, recognizing that the leukemia cells are in fact our own cells, and they sometimes know how to live in symbiosis with the body, and can actually not cause clinical problems for years and years.
And so one has to then concern themselves with whether it's important to start therapy, and I subscribe to the notion that there is no therapy without side effects. There is no therapy that doesn't have some downside, and so it's very difficult then to assess the risk/benefit ratio, even if the risk is actually quite considered low. How do you put that into the equation if, for example, the patient is felt to have very stable disease that may not require therapy, they're feeling great and leading a normal life?
So this is still a problem today. We do see this with patients, and I've seen patients who have maintained themselves, and they have some progression but then hit a plateau, and they may have that plateau maintained for quite some time, years if not longer, and they have no ill-toward consequences of disease. And so it tumbled me into thinking we really don't know.
And so all I can say is that let's be smart about this. We know that, for example, it's been recently observed people who analyzed DNA not only in our body but also in our fecal material, and they have established what is called a microbiome, which is the DNA of the bacteria. It's actually been found that we have more bacteria in our body than we have human cells. So you can ask, are we walking columns of bacteria?
But the important take-home message here is that the microbiome, in other words, the colony of bacteria in our GI tract is fairly fixed month to month to month. It's only when we take things like antibiotics that we put a monkey wrench into the microbiome, and that can cause problems if, for example, the wrong type of bacteria come along they may then establish a foothold in our GI tract and that can cause symptoms or even inflammatory conditions or irritable bowel syndrome.
So, in other words, the bacteria can actually serve as good bacteria keeping the bad guys out, and we've seen in treating patients with certain kinds of therapy that we may introduce a bottleneck where when we select out subclones which are lurking that are a small subset of cells within the clone that actually may subside over time because the other leukemia cells may be crowding them out. This is a very crazy notion, but when you think about this…
…can you balance this.
Yeah. So the oath you take, doctors take, is Do No Harm, so that's the whole idea, right?
Don't upset the apple cart, and you don't feel in CLL that there's a penalty for waiting for things are stable.
I think that that's true, and until we do studies that prove to the contrary we do have some investigations ongoing where patients with factors or markers that will tend to indicate the disease will progress more rapidly, but I must say I have had patients with those same markers who have been actually going without therapy for many years. So it's not a slam dunk.
Like the 17p deletion.
Especially the 17p deletion. In fact the deletion at 17p, although it's very important for governing the response to chemotherapy, it may not be the same for governing the progression of the disease. So I think it's important that if one is found to have deletion 17p to not panic, to not race into some form of therapy but to do some homework and find out what therapies should be taken that may not make the disease worse.