An Interview from ASCO 2016 with Dr. John Pagel on the Education Session on CLL

Dr. John Pagel was one of the presenters in an all-star panel on CLL management and controversy at ASCO 2016. While the annual ASCO (American Society of Clinical Oncology) meeting is really more about solid tumors, there is still some important session related to CLL.

Drs. John Pagel, Michael Hallek of the U. of Cologne, Germany, and Jennifer Brown from Dana Farber covered the following topics and more.

Take Away Points:

• “Watch and Wait” is still the best path for most patients outside of a clinical trial. For when CLL does need treatment, please see this article.
• For some patients who have excellent prognostic factor (mutated and no bad deletions by FISH- for a basic primer start here), FCR, the best studied chemo-immunotherapy (CIT) may be an excellent choice with a good chance for very durable responses. More on this here.

Questions:

• What do we do when patients relapse on the novel agents?
• Can we stop taking the novel agents?
• How can we better handle Richter’s Transformation?
• What is the role of CAR-T and allogeneic stem cell transplant (Click here for a glossary of transplant terms?

You can read my interview here or watch the video below.

Dr. Brian Koffman: Hi, I am Dr. Brian Koffman. I’m a family doctor, turned CLL patient, and I’m the volunteer Medical Director of the not-for-profit CLL Society. I am here in Copenhagen for the European Hematology Association (EHA) and really excited to be here with my long-time friend Dr. John Pagel. Dr.Pagel, would you like to introduce yourself?

Dr. John Pagel: Sure, great!  Dr. Koffman it’s nice to be with you, as always. I’ve been with you here doing this several times. I am a CLL doctor in Seattle, Washington, at the Swedish Cancer Institute and excited to be here.

BK: Well, Dr. Pagel, I wanted to ask you about ASCO and one of the crazy things is that ASCO (American Society of Clinical Oncology) and EHA kind of overlap on each other.  You presented the educational forum for the general community of hematologists and oncologists in terms of CLL and I’m wondering what you emphasized, what you think is important and trends that every community hematologist, oncologist, and every patient should know about CLL that’s different now than it was a year ago.

JP: You bet. Well, as you know, ASCO was just last week in Chicago and now we’re here in Copenhagen.

BK: A little jet lagged, both of us.

JP: Yes, doing okay though. But really, ASCO had a limited focus on blood cancers and in particular CLL, but we had a major educational session, a focused forum, there that I was lucky enough to be part of. I participated in that with Dr. Michael Hallek, who is the leader of the German CLL Study Group, as well as Dr. Jennifer Brown from Dana Farber Cancer Institute. And, we really gave…

BK: it’s a pretty strong team.

JP: It was a fabulous event. It was really directed towards community oncologists, and what we tried to do is really address the controversies. The focus was on moving forward and the questions that we need to answer, and really where we’re at today in 2016 and how we should be treating patients. So let’s talk about some of those things. I think one of the things to remember is that “watching and waiting,” still in 2016 with all the great new drugs that we have, is still very appropriate. So until you have a really good reason to get treated, it’s still appropriate to hold off on treatment.

BK: Let me push you on that because I know there are at least two clinical trials now looking at comparing novel agents with “watching and waiting.” In the past, we haven’t had such good choices. For the high-risk patients, I think Dr. Michael Hallek is doing a trial in Germany and Dr. John Byrd at Ohio State I think is also doing a trial to look at that.  So I would say outside of a clinical trial, it is still “watch and wait.” 

JP: And I should have said that. Certainly, the clinical trials are very important to help us answer these questions, where we could do something. That is a very reasonable approach with relatively low toxicity therapies that could have a major benefit in changing the natural history of CLL. But until we have that data, outside of a clinical trial, “watch and wait” is still appropriate. The other things to say are that chemotherapy and chemo-immunotherapy of course with an anti-CD20 antibody is still very appropriate for the right patients. Of course, those are patients with lower-risk disease that are not with a 17p deletion, or those with a mutated IGHV, as your audience knows much about that. Those patients can actually do extremely well with chemo-immunotherapy and in particular, FCR. Dr. Hallek led that discussion and I think that message is still critically important. Dr. Brown talked a lot about…

BK: Just following up on that. We’ve now got people that are a dozen years out that have no evidence of disease, from six months of chemo and immunotherapy. That’s pretty impressive.

JP: It is impressive, but it’s important to remember who those patients are. They’re the low-risk patients. They are patients who need treatment, no question, but they don’t have the high-risk features that I just alluded to. The other thing that we focused a lot on, of course, and Dr. Brown led the discussion, was primarily on the new novel agents, and really made sure that the community understands how to use those drugs because that’s where they are going to be delivered more and more, not in major academic centers. I spent quite a bit of time in the symposium talking about the newer controversies and the questions that are still unanswered, and where we need to go. There are a lot of questions and we have a lot of research that needs to be done. One of the major questions is “what do we do when patients stop responding to one drug?” For instance, Ibrutinib, when patients might become resistant. How do we overcome resistance?  In fact, can we actually just change the class of drug, maybe even stay in the same class? Can we actually treat someone with Idelalisib and rescue them from a failure to Ibrutinib? Or, do we they need to switch to a different kind of drug and does that work, such as Venetoclax or the BCL-2 inhibitor? Those are questions that we still don’t know well but we did summarize early data, primarily data that we had from ASH last December, important studies in a variety of ways.  We also wanted to a talk a little about the idea of actually being able to stop therapy at some point. All of our therapies with these drugs to this point are using them indefinitely, but certainly people can get to remissions. And in fact we are learning with some agents, in particular Venetoclax, they might get to a complete remission and not just a complete remission, but they might not have any evidence of disease in their marrow at the molecular level, something we call MRD negative or Minimal Residual Disease. And we’ve talked about that being an end point where, for those patients, if we’re able to achieve that, might be able to stop the drug. And, if their disease comes back, or when it comes back, get re-challenged with perhaps even the same drug. We have some early inklings that suggest that those people will still respond in that kind of a setting.

BK: That’s exciting, that’s really exciting.

JP: And I think we have lots of exciting things to continue to explore and we need to do better. We need to do better with things like overcoming Richter’s Syndrome and how to address that with new drugs, and what the new agents will do there. And we talked a lot about CAR-T Cell Therapy, as well, and the promise for CLL and CAR-T Cell Therapy.

BK: What’s your take on CAR-T right now? I know that some of those responses when people do respond can be very impressive and pretty durable. But the response rates I thought have been kind of disappointing in CLL, maybe because of our exhausted T-Cells. I know this is an area of expertise of yours. Where do you see that right now?

JP: I think we’re still gaining information. I think it’s very promising. Certainly I think we going to have a role for CAR-T Cell in CLL Therapy that will expand over time, but it won’t be something that will be universally adopted for every patient, even though I do believe in the right patient, it can be potentially curative. But to get a little bit more to your question, where do I see it, we need a lot more research to improve those response rates and to do it more safely, no question about it. So I think we’ve got a lot more research. It’s not something that I would explore early on in anybody’s disease. I’m not even particularly a proponent of it in early 17p deletion. We have a lot of work to do, and it’s appropriate in the right patient at the right time.

BK: Let me ask you something that’s another area of your expertise that you haven’t mentioned, is transplants.  Is there still a role for allogeneic transplants in CLL?

JP: So that’s a controversial and important question.  I think there is still a role, of course, I’m a transplanter so I’m going to say that, as well. But clearly the allogeneic transplant is the ultimate immunotherapy and it does work, but it comes with a heavy cost, and that’s a lot of morbidity and even the risk of taking a significant chance of dying from the therapeutic intervention. So we’re still doing transplants but those are for people that are younger, like yourself. Those are people that can tolerate this kind of thing and I think the numbers of those that we’re seeing are going to go down, more and more, because people are living longer without having to go to transplant. It’s an exciting time with all these other drugs and I think we’ve got a long way to go still to figure out a way to use allogeneic transplant for these patients.

BK: Any final thoughts or message that you want to give to patients from ASCO?

JP: I think the thing that we want to say to patients is that we’re continuing to advance this field rapidly. It’s incredible what we are doing, and what we have done. So what’s next?  It’s more clinical trials. It’s more randomized advanced clinical trials. It’s fewer smaller phase two single arm studies. It’s more investigation of the novel agents, and it’s really trying to get these into patients and affect people’s lives as fast as possible.

BK: Dr. Pagel, I always learn something.  Thanks so much.

JP: It’s my pleasure, Dr. Koffman.  Nice to be with you.

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Dr. John Pagel is Chief of the hematologic malignancy program at the Swedish Cancer Institute in Seattle, WA.

Dr. Brian Koffman, a well-known doctor, educator and clinical professor turned patient has dedicated himself to teaching and helping the CLL community since his diagnosis in 2005. He serves as the unpaid medical director of the CLL Society Inc.

Originally published in The CLL Tribune Q3 2016.