Dr. Michael Keating: My Hopes for the Future of CLL Treatment Recorded on December 8, 2014

Transcription

1 Patient Power Knowledge. Confidence. Hope. Dr. Michael Keating: My Hopes for the Future of CLL Treatment Recorded on December 8, 2014 Michael Keating, MB, BS Professor of Medicine, Department of Leukemia MD Anderson Cancer Center Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. Welcome to Patient Power. I'm Andrew Schorr, and we're in San Francisco at the American Society of Hematology meeting. It gives us a chance to get together with old friends and in some cases providers, in my case, one in particular, who I believe has saved and lengthened my life. As some people know, in 1996 I was diagnosed with chronic lymphocytic leukemia, CLL. And by connecting with other patients, those other patients said, you know, you need to go from your home city and maybe go to another city where they specialize in what you've got and see a doctor who is a specialist in that. I went to Houston, Texas. I went to MD Anderson Cancer Center, and I want you to see who I met 18 years ago, and that's Dr. Michael Keating. Michael. Andrew. Pleasure to see you. Great to be here. And so I want to reminisce with you a little bit. We have an 18-year history, and things are changing for you, and we have sort of a wide, long view. When I saw you in 1996, I was worried that I'd be dead, you know, because I didn't know the difference between chronic leukemias and acute leukemias. There was a man in Seattle, very prominent, who died of an acute leukemia. I thought that was me. And my community oncologist, well-meaning at that time, was saying, you need fludarabine (Fludara ) and cyclophosphamide (Cytoxan ) right now. And you looked at all the bone marrow results, and you said no. And you said, I think I'll have something better, and you don't need treatment right away. And if you do, we may have a trial. And my wife said to you, I don't know if you remember this, said, Dr. Keating, we had thought about having a third child, but we don't know Andrew's future. And you gave her a hug, as you do with so many people, and you said, go have your baby. Which I still say, folks, we should have named the kid Michael. We didn't. Okay. All right. So we've come a long way, and at the time when I interviewed you, too, for other patients you said, well, I'm not going to retire, I'm trying not to retire until CLL is cured.

2 Yes. Okay. We've come a long way. As you look back over the progress and younger doctors coming along, how do you feel about things? It's time for the knock-out punch, because I think we've already got to the point where in the study that you were on which started about 16 years ago we still have a third of the patients that have never relapsed getting out to 11 to 16 years. I've never had any more treatment for it. So that and we can't find any leukemia in the vast majority of those patients, so it's a functional cure. The patients are well. They've been off treatment for 12, 13, 14, 15, years, etc., and they have never needed to have anything else. And we've got a pretty good idea as to which group of patients they happen to be. Right. This was FCR. Yes. And the FCR has been approved as the standard for younger, fit patients, and I've now certainly got to the stage where I'm no longer younger and no longer as fit as I once was. But there's a changing of the whole mentality. I think that the FCR leveraged us into the point where we said a number of patients are probably cured at the present time with FCR. And we now know that we can get away with starting patients off on different treatments that's not chemotherapy and not do them any harm. And, fortunately, we have a number of very, very active drugs at the present time that have come along that are oral. They're well tolerated. Patients can be treated up into their 90s with them, and they begin to feel well in a very short period of time. It doesn't damage the normal things that chemotherapy does. So I said that I oh, about four years and three or four months ago that I needed five years, and I think by the end of August all of the cure strategies will be put in place. And we just need the young people to watch what happens and cheer the success of them. Now, you've been very devoted. You have a foundation, CLL Global, and you've really tried to make this a worldwide effort in bringing doctors together in collaboration, and that probably when you started in your career doctors didn't, researchers didn't collaborate so much. But now there seems to be a sharing of information, a true community working together, the patients, too, and that must be satisfying to you. It's very satisfying, and one of the gifts was that I was fired from acute leukemia and I had to find something to do so that I went to the CLL, because nothing much was happening. Fludarabine was the start of the change. And the thing that was totally unique about the CLL community was that they were truly collegial. They celebrated every success that any one of them had, because there were very few successes at that time. And by and large that attitude has been maintained in CLL ever since. And I think part of it is due to the leadership of Professor Jacques-Louis Binet in Europe and Canty Rye in the United States, who really established this whole sense of we can do more together than we can by ourselves. And it was a change, because the acute leukemia area was very, very competitive. Everyone wanted to be number one, and it was just not as nice.

3 The wonderful thing about dealing with CLL is that you really do get to know your patients as people. So, you know, I tell the story many times about how your wife said, what about going for number three, and I thought that's what life is all about. And it can't be measured by longevity totally, and so we just have to get to know what people want. I should mention that your daughter is in hematology/oncology, so it's a family affair. So it's been the Keatings have been very devoted to us patients, and we've developed these relationships. So there's discussion now is can we get to a cure, you were mentioning that, and exciting medicines to keep CLL truly chronic and live better. But do you think we'll get to the point where maybe with some combination medicines or something next where someone, like I was able to do with FCR but for other people on oral therapies, where not only do we knock the disease down but we knock it out? I think it's very, very likely. I think in the vast, vast majority of patients now even with some of the single agents, the new agents, we can get to the point where there's just a small amount of disease left behind so that there are a number of prospects after that. There are other drugs that come along that we are a little nervous about using them when there's a lot of disease, but they're tailor-made for the situation where there's a very small amount of tumor left behind. And these were the Bcl-2 inhibitors that the ABT-199 and now they've given it a name, which I can't remember yet, and but the combination of ibrutinib and agents like this are already in the planning phase. And I think that it is really getting to the point where the majority of patients after a period of 12 months we will not be able to find any sign of the disease. Now, I remember years ago when I was first starting the FCR trial, and I can't remember the patient's name, but he I saw him while I was going through treatment, and he was a sick guy. And he had probably much more aggressive CLL, and he passed on. And, unfortunately, we all know that's happened, and there have been versions of CLL that have just been harder electro treat. Yes. So while we talk about progress for so many people, for those people with certain mutations where what do we have for them now to help them really do better and have the same hope that many others have had? The major problem child is people that have lost part of chromosome 17 as detected on the FISH test, or have a mutation in the gene that's associated with that, namely p53, and those patients have not done well on chemotherapy. Chemotherapy just doesn't work very well, and it's not very well tolerated. But now we have ibrutinib (Imbruvica) and idelalisib (Zydelig) and AB-T199 that are all effective in that disease. But as we get more experienced with it, we find that a certain number of patients after about 12 months will develop transformations and/or aggressive lymphoma, or they will just have a difficulty in tolerating the drugs. But with 12 months we can get to the point where they can be candidates for allogeneic stem cell transplants, the mini transplants which are potentially curative. The chimeric antigen receptor educated T cells have the potential to eradicate not only the residual disease in the 17p group of patients but generally, and so that we have brought the point where the patients are feeling better, their counts are better, their organ function's better, and they will tolerate these transplants better until we don't need transplants anymore. Now, looking to the future there's a lot of buzz. There's a lot of research starting now at the MD Anderson too related to the sort of burgeoning field of immuno-oncology. Now, CAR T-cell therapy is part of that but not only. We've heard terms like PD-1 and PDL-1, and it's been applying in solid tumors but applying here, too. Where as I understand it where your

4 immune system can sort of wake up and it can see the cancer cells and do the job that it didn't do when you developed cancer first. Are you excited about that? Extremely excited. The transformation that has come about with just single antibody therapy in melanoma and lung and kidney cancer, etc., are truly spectacular so that we've got from a, in a subset of high-risk patients, from 3 percent five-year disease-free to 20 percent. And when you put two of these agents together, it gets up to about 35 percent, and that really is something that we've never seen before. And at this meeting, there have been a couple of presentations in Hodgkin's disease where just using one of these checkpoint inhibitor antibodies the vast majority of patients are responding with advanced disease and getting complete remissions. And to let you know how we sort of envision this, it's the cancer cell, whether it be CLL, leukemia, lymphoma or Hodgkin's solid tumors, is sitting there, and there are chemicals on the surface that trap the immune cells. So the immune cell's in this death hug so that they can't do anything. But this wakes them up, breaks them apart so that the immune system has been trying to kill the cancer cell but hasn't been able to get the job done. We know that CLL is a very good target for immunotherapy, because it can be cured quite consistently with substantial risk by using allogeneic stem cell transplant where you put in a new immune system. Now I think that we have the right target. We have the right group of chemicals to look at. There's another drug which is obinuntuzumab (Gazyva ), which has just been approved for acute lymphocytic leukemia. And that's got a molecule on one end which will attach to the ALL cells but also the CLL cells and another molecule at the other end that attaches to the immune T cells, so that the success in ALL I'm sure will be translated into the same sort of success. So it's not a question of are we going to cure CLL and leave the patient with no disease? The question is what percentage of the patients will be cured? And I predict that in five years time probably about 80 to 90 percent of the patients will be free of detectable leukemia. Wow. Okay. Well, my mother-in-law would always say, from your lips to God's ear. He listens. We just don't talk to him very much sometimes. So, Michael, just a couple of other things, just to be clear for people. You've given up a lot of the administrative stuff you've been involved in. You're still seeing patients. Are you going to keep on for a while? Yes. I've cut back to four clinic days a week, because I want to have I still see the same number of patients during the week. They're just crowded in a little more. But I want to have Friday as thinking day. Good for you. And I want to spend more time developing the next generation of CLL physicians, because they'll be using technology that wasn't even imagined when I was going through medical school. Medical school in Australia was that's when they were developing the code for DNA and look how far things have come in that period of time in one career. I want to think back with you for a second. So when you started your career with leukemias, unfortunately a lot of people passed on.

5 Almost all. And now I'm here and many others we can think about, and you see us living well. How are you feeling about that? I feel some happiness, but I still am angry that we're not doing better, and the fire still has to keep burning. And I hope that what's happening in medicine these days doesn't quench the fire on people, because we have to let them run as fast as they can and get the obstacles out of the way. Because there's a ton of talent, there's a ton of technology, there's a ton of creativity, and we just need to harness it, because it's one of the things that doctors do best. They chase the enemy, and they like to kill it. One of the areas that I think is very gratifying is that patients are living well, but they always have at the back of their mind they're not quite normal. And we have the likelihood of getting a number of skin cancers and other cancers, etc. So now that people are living longer we don't say, okay, getting rid of the leukemia is the only thing that we want to achieve. We need to see if we can normalize their immune system, detect emerging second cancers early so that we can stop them from limiting their life, and just just give them everything that we can. Well, you've been instrumental in so much of this, Michael, and you know from me and from Esther and from that kid who is on earth, Aton, who wouldn't have been here had you not given us the confidence to go forward, I want to thank you from the bottom of my heart. But not just me. Someone else who works with us, Carol Preston, is another one of your patients. Carol has been living with CLL, and so we want to stay here, Carol. Stay here. Have a seat, Carol. Maybe you can just scooch down for a second. I want you to just come between us. So this is what it's about, right, Michael? It is. Because Carol, when she first came down, she's a very intense lady. She has high levels of expectation. But it's been wonderful to see the sense of serenity increase. The longer she's in remission, the better she feels, looking forward to doing new things in her life. It's just wonderful. And devoted to patients, with us with Patient Power. Carol Preston: And since I first saw you I've probably traveled to 12 or 14 countries, so I haven't I have itchy feet. Well, there are many more countries, so... Michael, thank you. I'm going to give him a hug on camera here, folks. This is what we do with this guy. Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, contributors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you.