[ Inglés] Non-Hodgkin Lymphoma Updates From an Expert

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Topics include: Treatments

Dr. Joshua Brody from Mount Sinai School of Medicine joined Patient Power to provide an update in non-Hodgkin lymphoma research. Have new avenues in treatment been created? Dr. Brody shares data collected on novel agents like monoclonal antibodies, anti-body drug conjugate and immunotherapy approaches for those living with non-Hodgkin lymphoma. How can patients with more aggressive conditions access promising new therapies? Dr. Brody also discusses unprecedented results from clinical trials on CAR T-cell therapy for diffuse large B-cell lymphoma, recent FDA approvals, and where research is headed next. How durable is the patient response from these innovative strategies? What are the next generation of treatments focused on? Watch now to stay informed with current treatment and research news. 

 

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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.  We're talking about lymphoma, particularly non-Hodgkin lymphoma, which is a big group of lymphomas, and with us is a noted expert in the field from New York City, Dr. Joshua Brody, who joins us from Mount Sinai, New York.  Dr. Brody, thank you for being with us. 

Dr. Brody:

Andrew, thank you for having me. 

Andrew Schorr:

So let's start with where all the buzz is about for maybe some of the sickest patients with some acute lymphomas and also diffuse large B-cell lymphoma, CAR T-cell therapy, chimeric antigen receptor T-cell therapy.  Some approved drugs, lots of trials.  Tell us about at where you think we are now with whether it's version 1.0 or moving to a 2.0 or a 3.0, and how it could apply to more people. 

Dr. Brody:

Yeah, absolutely, Andrew.  This is so exciting when I describe this therapy to my patients I swear to God it sounds like science fiction.  It sounds like this is Star Trek medicine.  I mean, this is the step right before the little phaser beam that just makes people healthy.  It's almost that amazing. 

We literally, as you described before on the show, take patients' own immune cells, take some of them out of the body.  We put a novel gene into those cells that allows these immune cells, these T cells, to go back into the body, traffic and find lymphoma wherever it may be hiding, and eliminate those cells and literally melt away large tumors.  This has been an idea for a long time. 

It got a great boost about 11 years ago with progress made in the basic science in the labs of the pioneers of the therapy and just over the past couple of years has shown literally unprecedented results in patients with aggressive lymphomas, especially diffuse large B-cell lymphoma, and just in the last year leading to approval of anti-CD 19 CAR-T cells from a company Kite Gilead and from the company Novartis and probably a third one from a company, Juno, coming around the corner. 

And these are for patients with diffuse large B-cell lymphoma for whom all of the standard therapies have failed, chemo-immunotherapy, autologous stem cell transplant, and those patients really in 2016 we said to them they have an incurable disease, and now we have a pretty good inkling that they may have a potentially curable disease.  Some of the patients on these trials, about a third of them, maybe 40 percent of them, seem to have long remissions, and that is where cure starts. 

Those remissions might last forever and those patients might be cured.  So far, it's actually looking like that.  So very exciting, practice-changing absolutely and from a scientific perspective miraculous that we can think up an idea like this and make it become real.  It's inspiring. 

Andrew Schorr:

So, Dr. Brody, though, for a broader range of lymphomas it's still experimental, and you have some trials going on.  Talk about where the research is headed so we can get to sort of CAR-T 3.0…

Dr. Brody:

Absolutely. 

Andrew Schorr:

…where you know who is it right for, what conditions, how to manage it as well because I know there's been a concern along the way for cytokine release syndrome and how to manage that.  Could this be done not just in a big center like yours but more broadly where many patients are treated even in the community? 

Dr. Brody:

Oh, absolutely.  So many ways for this promising therapy to advance not in 20 years but in the next couple of years.  So the first is just to take these sickest patients, the patients with aggressive diffuse large-cell lymphoma and get more of them access to this therapy.  

The first way to do that is not just to use it for third-line therapy but to try to bring it even sooner for the patients with the worst disease.  So there's an ongoing trial for patients with second-line diffuse large B-cell lymphoma.  There will be a couple of these. 

The first one is called Zuma 7 where we're actually randomizing patients with the standard therapy versus CAR T-cell therapy.  It's early to say what will happen with that trial, but I have a personal belief that that trial will be a blowout, and CAR-T cells will be drastically superior to the standard therapy in that specific setting.  So that's very promising getting more access to these therapies for those patients with the most aggressive disease. 

But then that's the same CAR-T cell.  How can we actually make that cell better?  You hinted at one of the worst problems, which is we do not want to oversell this therapy.  It is elegant, but it is not benign.  It has some of these risks you alluded to, one called cytokine release syndrome, CRS, another one, the central nervous system toxicities, we just call them CNS adverse events.  Both of those can be serious.  They can land patients in the intensive care unit. 

Occasionally, they can be lethal.  We had in the first trial of a hundred patients a couple patients that died from the therapy.  So it has real risks.  Two out of a hundred has a lot of room for improvement still.  So generation 3.0 CAR-T cell is going to in my opinion, first focus on that safety aspect.  We can both improve the safety and sort of personalize the therapy much better.  We can insert another gene into these immune cells, which we call a modulator switch or a dimmer switch or a suicide switch that can turn off the CAR-T cell when it becomes hyperactivated and starts causing these toxicities. 

And the really elegant aspect of it is that we don't have to wait for these toxicities to occur.  If certain signs from things, blood tests, that show that those toxicities are going to occur in the next two or three days we can start to tamp down those CAR-T cells before they cause toxicity, keep patients out of the intensive care unit.  And what really what that will do is increase opportunity for patients to get treated, as you say, not just in transplant centers but eventually maybe even as an outpatient therapy so patients wouldn't have to go to the hospital at all. 

Andrew Schorr:

Okay.  So you're doing this in a certain select group of lymphomas.  So there are people watching who may have other less aggressive lymphomas but they say, will this be refined to a place where this will be a reasonable therapy for me? 

Dr. Brody:

Absolutely.  I mean really we did start with some of the most aggressive lymphomas, the patients with DLBCL that hasn't responded to therapies.  We have early data in a few of the others.  They have early data in mantle cell lymphoma, which is a pretty aggressive lymphoma, and we have open trials now, we're treating more of those patients.  We already have a very strong hint that the therapy is comparably impressive at getting many durable responses that are last for months and probably years in mantle cell lymphoma.  A few little pieces of data in follicular lymphoma as well, and also in CLL where the start was actually slow but now we're having some promising results.  So those are the most common types of lymphoma. 

If the things can work there, they should be able to work in marginal zone lymphoma, Waldenstrom's macroglobulinemia, other things as well.  What we haven't made much headway with yet, and I really I think a next big direction is getting to another terrible type of lymphoma called T-cell lymphomas.  And those patients don't have great options after the first therapies can fail, so now we have some very early trials of getting CAR-T cells to fight T-cell lymphoma as well. 

Andrew Schorr:

That would be great.  So there's another area of medicine called antibody drug conjugates where you can bring a much higher payload of medicine right to the cancer cell, and you've been doing this in Hodgkin lymphoma.  Does it apply to these other non-Hodgkin lymphomas? 

Dr. Brody:

So this is an elegant approach, and it makes sense.  Instead of just giving chemotherapy to the whole person, we attach the chemotherapy to the tail end of an antibody, antibody brings the chemotherapy directly to the tumor cell and delivers it locally.  Elegant idea.  As you say, it's been already great success in Hodgkin's lymphoma, also in breast cancer and some other tumors as well, so there's no reason it can't work here, in NHL. 

So far the best progress is with a couple of targets, CD19, just like with CAR-T cells what we're targeting.  We have an antibody drug conjugate that we saw early results at ASH 2017, a medicine called ABCT 401.  You know, these things are so early we just give them an alphabet soup name before getting them an even more confusing name later on. 

And then another antibody drug conjugate called polatuzumab targeting CD79.  Is so these are both targets that are universally on B-cell non-Hodgkin lymphomas, whether they be DLBCL, follicular lymphoma, even CLL, SLL.  And so those therapies could be great for all of these types of lymphomas.  So far the best results for polatuzumab vedotin, CD79, ADC, antibody drug conjugate, has been in diffuse large-cell lymphoma.  And ASH 2017, randomized Phase II trial. 

So once these trials become randomized we have to take them much more seriously because we're really seeing the benefit head to head compared to some other standard therapy.  And rituximab (Rituxan) bendamustine (Treanda), very standard therapy, when we added that antibody drug conjugate to it, drastic improvement.  So that one probably will be a real-term change for people with DLBCL in the next couple of years, and the CD19 antibody drug conjugate is probably not far behind. 

Andrew Schorr:

Okay.  One other area I want to ask you about is I guess what you'd call immunotherapy.  So people see the ads for lung cancer drugs now, for these checkpoint inhibitors or PD-L1 inhibitors and all that, and there are many companies developing this.  Does this apply to the non-Hodgkin lymphomas? 

Dr. Brody:

So quite—to be fair in the non-lymphoma realm of oncology this is maybe the greatest advance in 40 years or maybe ever, since the invention of chemotherapy in the 70s at least, and yet in lymphoma we hear about this a lot in the context of Hodgkin lymphoma, but much less so in most types of NHL.  There are a few NHLs which are responsive to those checkpoint inhibitors, but the majority have been at best only slightly responsive. 

So the question is do those things just not work, or do we just need to combine them in a thoughtful way to make them work?  And I have to tell you I'm pretty sure the answer is the latter, that if we can get the T cells, get the immune started in killing indolent NHLs like follicular, SLL, CLL, or get the immune system started to killing DLBCL, then those checkpoint inhibitors, those PD-1 antibodies, sometimes call them the Jimmy Carter medicines, because that's what Jimmy Carter got when he had terrible melanoma even metastasized to his brain.  I'm not Jimmy's doctor, but I understand that Jimmy is doing very well. 

So if we can get those kind of durable remissions combining PD-1 antibodies with other immune therapies, and that's been a focus for us here at the Tisch Cancer Institute, because we are very lucky to have immunotherapy as a core part of our NCI grant. 

So we have a couple of combination therapies for low-grade lymphoma.  One of them is combining those PD-1 antibodies with a vaccine for follicular lymphoma, SLL and also marginal zone lymphoma, and we have a very different approach for patients with aggressive lymphoma, something we call immunotransplant.  We use those checkpoint inhibitor antibodies, and this is the transplant part, we basically combined it with a way of taking out patients' immune cells, giving them a clean slate immune system and then put in those primed immune cells, those anti-cancer immune cells back in after they have a clean slate. 

And the lab that has been gangbusters in making aggressive lymphomas melt away, and we've just started treating patients in the last few months with that immunotransplant approach.  So, so far promising.  So far seems to be safe.  I think it's a great opportunity to try to get patients' immune systems to kill their own cancer cells. 

Andrew Schorr:

Very exciting.  So I think the advice for patients is depending upon which lymphoma you're living with and how aggressive will mean how much time you have to learn about this and think about this.  But the field is changing, folks, and so you need to connect—maybe get a second opinion with a doctor like Dr. Brody, check in with a center that's doing research, see whether this applies to you.  Dr. Brody, am I on the right track? 

Dr. Brody:

And I think second and third opinions for patients that have time to get them are always a good idea.  And let me just say personally as doctors we have very little ego involved in this.  When my patients have a tough decision I'm delighted for them to go and meet doctors from Cornell, Sloan Kettering, NYU, Montefiore, anywhere around to get their thoughts as well because my colleagues are brilliant and lovely.  And, similarly, I think it's always safe and reasonable to get additional opinions when there are a few choices.  Yeah, I think it's a good idea. 

Andrew Schorr:

Right.  Well—my ears perked up when you mentioned marginal zone lymphoma.  I have a friend in Boston with that, and the guy is really plugged in, and I'm sure he's going to watch this program to see is there something he should be finding out about that could apply to him. 

Dr. Brody:

Absolutely.

Andrew Schorr:

Well, Dr. Joshua Brody from Mount Sinai in New York, thank you so much for being with us and filling us in on kind of a broad brush of what's going on, what could be promising, what is promising in NHL.  Thank you so much for being with us. 

Dr. Brody:

Andrew, it's my pleasure.  Thank you. 

Andrew Schorr:

Andrew Schorr reminding you that 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 November 12, 2018