Novel Therapies for Follicular Lymphoma: Where Are We Now?

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Topics include: Treatment and Understanding

Interest and excitement around the treatment of follicular and indolent lymphomas has been buzzing with patients and  physicians alike. What is the excitement all about? Experts gathered in September 2014 in Scottsdale, Arizona at the International Workshop on Non-Hodgkin Lymphoma (iwNHL) to discuss and debate emerging research. In this video, Drs. John Gribben from the Barts Cancer Center in London and Wyndham Wilson from the National Cancer Institute in Washington, D.C. share the conversations from this meeting for patients, revealing a real optimism for patients with these diseases.

This program is sponsored by the Patient Empowerment Network, which received educational grants from Millennium: The Takeda Oncology Company, Seattle Genetics and Genentech.

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Transcript

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.

Andrew Schorr:

Hello and welcome to Patient Power. I’m Andrew Schorr.

Patients with follicular lymphoma are seeing a new world of treatments. What does it mean now and in the future?

We’re joined now by two experts in the field as they sat down at a recent conference called the International Workshop on NHL–Non-Hodgkin Lymphoma. They are Dr. John Gribben and Dr. Wyndham Wilson. Dr. Gribben, of course, is in London, and Dr. Wilson is at the National Cancer Institute outside of Washington, D.C.

Dr. Gribben:

What are the newer agents that are exciting you, both the ones recently approved as well as on the horizon that are exciting you for treating follicular lymphoma?

Dr. Wilson:                           

I think probably the most exciting group of agents come from our increasing understanding of what seems to be driving some of these tumors. One of the functions of the cell from which these cancers come from, which is a lymphocyte or one of the white cells, is to make antibodies. They actually have receptors on their surface, and they actually have signaling down through their cellular pathways. Studies have shown that this signaling is key to keeping these tumor cells alive. We now have a number of different drugs that can actually modulate that.

We have one called idelalisib (Zydelig). We have another one called, that we discussed earlier on, ibrutinib (Imbruvica).

We’re also understanding that immune modulation probably plays a role as well. Some of what we call the new checkpoint inhibitors, one of those actually just approved for a solid tumor, and then an IMiD, a drug such as lenalidomide (Revlimid) appear to be very effective as well.

Dr. Gribben:

In diffuse large B-cell lymphoma, we’re going for cure. You’ve talked about maybe we’ll be able to get to cure, but there’s a lot of talk now about living with and controlling the disease rather than necessarily, with what you and I have been spending many years of our life with, going to complete remissions. What do you think about this notion of moving a disease into a controllable disease that you live with some of these novel agents, rather than the approach of looking towards deep remissions and potential eradication of disease?

Dr. Wilson:

I think at the end of the day, the optimal therapy would be to try to cure it.

Dr. Gribben:

I think that for our patients it’s better to be cured and off therapy rather than to be continuing to take therapy, irrespective of how low the toxicity of the tablets may be.

Dr. Wilson:

But what I think has happened is that we’re coming up with new classes of agents, with the ones that I just discussed, the ones that are affecting the B-cell signaling. And these have actually been able to keep disease control for much longer than what we’re able to do with previous drugs. The other thing that really has changed is that we used to always treat these patients in pulses of therapy. We would give them a series of chemotherapy agents, we would stop and then we would wait, the disease would stay quiet and then, ultimately two or three years later or longer or sometimes not at all, but usually these disease would come back. With some of these newer classes of agents we’re giving, we’re giving them every single day. Patients are staying on them until the disease actually grows. We’re now finding that patients are on-therapy, in some cases, for years.

Dr. Gribben:

We’ve talked already about this as a disease, which the natural history is, at the moment at least, that patients are going to continue to relapse. What are the decisions that you make when you’re seeing a patient who’s relapsed with lymphoma whose requiring therapy. What are the decisions you make to decide the next line of therapy that should be given?

Dr. Wilson:

Obviously, I think very hard about what they’ve already had. I think about trying new classes of agents. But I think, and this is also key, to think about quality of life as well. This is where actually patients have had multiple runs of therapy. They may begin to think about more aggressive therapy such as autologous transplant, in some cases, or another type called allogeneic transplant, which is really a type of immune therapy. When you start to move, particularly into allogeneic transplant, you’re talking about a whole other level of toxicity, so we usually reserve that after most therapies have really run their course, but that’s really a two-edged sword. On one hand, it’s very toxic, and people actually die from it. But there’s also emerging evidence that immune therapy, allogeneic transplant, and now some newer therapies called CARs actually may be able to give the patients long-term control—very, very toxic, but at the same time may give a very long-term, positive outcome.

Dr. Gribben:

Now you’re already alluding to the fact that the immune system can be effective. A lot of data is emerging in this disease about the importance of not just the tumor cell itself but the microenvironment that it lives in and the ways in which we may be able to manipulate that using the immune system. There’s lots of agents, you mentioned the CAR T cells, where we’re talking about using the patients’ own autologous immune system to target it, checkpoint controls that you’ve also already mentioned, where you’re harnessing the patient’s immune system to tackle their cancer. I find that a lot of patients kind of like that approach of thinking that their own body is going to be involved in fighting the tumor. It’s been a hugely long journey in watching immune therapy go in and out of fashion; some very disappointing responses with vaccine. Do you think we’re now understanding more about the biology of the disease enough to believe that some of these new immunomodulatory agents are really going to impact the disease?

Dr. Wilson:

I think the short answer to that is yes. You’re right. There was a lot of excitement around vaccines, and there were some very, I’d say, interesting and real outcomes that patients benefited from them. It looks though that the vaccines really were most effective when they activated T cells, but they weren’t the most effective way of actually doing that. For our audience, it’s the T lymphocytes that are kind of the police that really go around and eradicate dangerous cancer cells. Now we have come up with much more effective ways of activating these. Allogeneic transplant is a very radical way by actually giving a new immune system that actually moves in and thinks everything is foreign. And the good news is that it thinks the tumor is foreign, so it kills the tumor. But if it thinks your liver is foreign too, that’s not a good thing. As you already mentioned, that we can now actually genetically modify a patient’s own T cells to make them much more active. We can also turn the brakes off the normal T cells using what we’re now calling checkpoint inhibitors to simply make the entire T-cell system much more active. Over the last two or three years, both CARS and these checkpoint inhibitors have really come a long way. I think that the outcomes that we’re seeing now, although early, is extremely favorable.

Dr. Gribben:

One of the challenges we face, of course, or patients face, is that there are a whole variety of new, novel agents out there in clinical trials. How do patients choose and work their way through what’s the right trial for me to be considering at this point in my disease?

Dr. Wilson:

I think it really gets at again whether they’re early on in their disease versus later, quality-of-life issues. I would say that we’ve been able to dial back chemotherapy as we’ve put in some of these targeted agents that are very well tolerated, whereas we might have only used those in people that have had multiple therapies now. We’ve shown that they’re relatively safe and that they’re quite effective. So those drugs in combinations are being moved up sooner. I would say that patients should be looking out for some of these newer combinations, and many of them can be had on a clinical trial. As we begin to move through and patients have had multiple therapies, then I think it’s very realistic to begin to think about some of these immune therapies as well, such as CARs. Unlike allogeneic transplant, which was really the only aggressive T-cell therapies, both CARs but particularly checkpoint inhibitors look like much more friendly ways. Mostly the checkpoint inhibitors. CARs can still have their own downside.

Dr. Gribben:

In summary, we’re talking about a disease that’s going to have a remitting and relapsing and course. Patients are going to know and understand a lot more about their disease and have lots of opportunity to discuss with their clinical team, what’s the right way to move forward. You’ll agree with me: a very exciting time in terms of the new agents that are available, and that’s obviously good for our patients in terms of thinking about going forward.  Again, as in other diseases, we’re starting to see lots of kinder, gentler therapies, many of which are going to be much better tolerated for, quite often, the more elderly patient population that haven’t always tolerated these conventional chemotherapies well.

Dr. Wilson:

I think I’d like to close with one comment is that when I first started in this field in the late 1980s, the average median time people lived with these is around 10 years, and we’re probably now up around 15 to 20 years. There have been concrete, very favorable changes. I also want to say that there are a fairly large segment of people that get therapy where the disease never comes back in their lifetime.  Given the fact that the average age for the more common types is around 60, I think many people with current therapies can, I think, be very optimistic that these will not be life-threatening diseases, that they can live long enough, and sometimes the disease never coming back. I think that patients should be very optimistic and not see a diagnosis of these as being something that’s really going to be transforming their life because most people generally will live a very good, positive life with them.

Andrew Schorr:

We have much more with these experts coming up for you and also interviews with other experts in lymphoma. Be sure to be signed up for alerts on our website, so you’ll know whenever we post something new.

I’m Andrew Schorr. Remember, knowledge can be the best medicine of all.

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.

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Page last updated on April 27, 2015