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Treating CLL With Immunotherapy: How Is Research Evolving, Chronic Lymphocytic Leukemia, Patient Power

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Chronic Lymphocytic Leukemia

Treating CLL With Immunotherapy: How Is Research Evolving?

Published on January 25, two thousand sixteen

How do checkpoint inhibitors apply in CLL? Where do we stand with CAR-T therapy? From the two thousand fifteen American Society of Hematology (ASH) meeting, CLL accomplished Dr. William Wierda shares his insights into this exploding field of research. Dr. Wierda discusses developing immunotherapy options, including CAR T-cell therapies, which he feels «…hold the most hope as a curative strategy for CLL….CAR T-cell therapy is the next step to cure patients with CLL.»


Prof. William Wierda

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Please reminisce the opinions voiced on Patient Power are not necessarily the views of our sponsors, contributors, fucking 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 adequate for you.

Hello and welcome to Patient Power. I`m Andrew Schorr. At the two thousand fifteen meeting of the American Society of Hematology, there was a lot of discussion about CLL. I got to sit down with a leading pro in the field. That`s Dr. Willam Wierda from MD Anderson Cancer Center in Houston.

I asked him about so-called checkpoint inhibitors. These are medicines that can manipulate the immune system to fight the cancer. How do they apply in CLL?

The solid tumor field is exploded with these checkpoint inhibitors. Fresh drugs that have been approved every week we hear about a fresh drug that`s been or a drug that`s been approved in another indication, a fresh drug approved or a drug that`s been approved in another indication in the solid tumors. These are antibodies that are directed against immune-modulating or immune-regulating proteins in T cells and in antigen-presenting cells.

And when patients with solid tumors have been given these drugs, they`ve seen remarkable responses–responses where, for example, in melanoma, patients were not expected to live beyond a year or two, and patients are living twenty five percent of them now are living out beyond three to five years. So they`re getting exceptional, very durable responses in the solid tumor setting with these checkpoint inhibitors. They`ve been slower to come to the hematologic malignancies. We at [MD] Anderson have been focused, and I`ve spent the last year working with a colleague of mine at [MD] Anderson by the name of Nitin Jain on opening protocols with these agents for patients with CLL.

We have a PD-1 antibody protocol that is now open, and we`re working on opening a PDL-1. PD-1 is the checkpoint inhibitor that the antibody trusses to. PDL-1 is the live-an that ties to the PD-1, which is voiced in T cells. So I`m very anxious and optimistic about this. This has been an area that I`ve been interested in for ten years. We published a paper many years ago on CTLA-4 and how it was overexpressed in patients with CLL, in the T cells of patients with CLL, and we could by using antibodies block CTLA-4 and demonstrate in the laboratory at least enhanced responses against the leukemia cells by the T cells.

So this is an area that I`ve been intrigued and interested in for a number of years. It`s gratifying to see eventually we`re able to begin testing these agents in patients with CLL. So there is one abstract with a drug called pembrolizumab (Keytruda) that`s being reported here at ASH. The Mayo Clinical Group has evaluated pembrolizumab in patients with non-Hodgkin`s lymphoma including some patients with CLL and Richter`s transformation in their reporting activity. So I`m anxious to get things rolling with these studies and to embark treating patients with the drugs to see what the effects are.

I also asked Dr. Wierda about another area of immuno-oncology, so-called CAR T-cell therapy. A duo years ago, there was a lot of hum about that. It`s still continuing. How about an update?

So this is another area that I`ve been interested in for a number of years, as you know, using these chimeric antigen receptors to redirect T cells to react and eliminate CLL cells. The proteins that have been the targets for the receptors included CD-19, and I`ve spent a number of years working with collaborators, Tom Kipps and Lawrence Cooper at [MD] Anderson, to develop ROR-1 CAR T-cell strategy. It`s a fresh area, it`s a fresh field. It requires fresh technology, fresh production. So far it`s been a patient-specific treatment that we have had to develop.

So there [have] been a number of challenges that have slowed the progress of this that are being addressed, and most of the activity right now in terms of clinical trials is happening in ALL, patients with acute lymphoblastic leukemia, with regard to the CD-19 CARS. There are companies such as Juno and Kitz and Novartis who have opened multicenter clinical trials with the CD-19 CAR that enrolling patients with ALL and patients with DLBCL or diffuse large B-cell lymphoma.

These companies have spent most of their resources to achieve this and to open these studies, and so that is why things have been a little bit slower I think in CLL because they`ve been focused so much on opening these studies and being able to address the enrollment needs for these studies with regard to ALL, at least for the CD-19 trials. Clearly, there`s activity with the CAR T-cell strategy in CLL, and that I think will translate into having a number of clinical trials open once we get past this phase of having them open and being able to address the needs for the ALL and DLBCL group.

And the same is true for ROR1, and Juno I know has been working on ROR1 strategy. We`ve been working for a number of years. Our academic efforts are a little bit slower and more challenging, because we don`t have the same funding as pharmaceutical companies do. And we have to ask [for] and write grants, and ask for funding to support those, and that cost listing is down. So the CAR T-cell strategy will happen. I think it`s a very reasonable treatment. I`m enthusiastic about this treatment as the next treatment for patients with CLL.

It is a treatment right now that does have side effects and complications that are not insignificant. And so I think that will be another challenge when we embark opening trials and treating patients with CLL with these CAR-T cells making them more tolerable and just a little bit safer so that we don`t see the same incidents of severe cytokine-release syndromes that are seen in the acute leukemia patients for CLL then it`ll become a more viable treatment and strategy. That`s a challenge if you have a patient who`s doing well on an ibrutinib (Imbruvica) if you`re talking about a treatment that twenty five percent of patients have a severe reaction it`s a difficult treatment.

I think it could potentially be–it`s among the treatment strategies that are in development. The CAR T-cell strategy right now I hold the most hope for as a curative strategy for CLL. I`m enthusiastic about the CAR T-cell and cellules therapy as the next step to cure patients with CLL or potentially one of the next steps. It works by a different mechanism of activity. Transplant we know is a cell-based strategy that we can eliminate disease and potentially cure them long term. And so the mechanism of activity is similar with the CAR T as it is with transplant, because you`re using immune cells to eliminate the leukemia cells. So I hold the most hope right now for cure of the disease with immune-based strategies, CAR T-cell strategies, perhaps the checkpoint inhibitors will see what the data looks like for the checkpoint inhibitors.

Eventually, I asked Dr. Wierda his perspective on how he thinks patients should be feeling about CLL today with the approved medicines and others that are very promising.

Today, I think for me the challenge in terms of research and what we do is how are we gonna cure patients? We have so many treatment options available. There are drugs that have non-overlapping toxicities that work by different mechanism of deeds, and we know information about how patients do, and they do exceptionally well long term when we use those agents alone. We haven`t even truly commenced those trials using combinations or using sequencing of these agents.

So I`m very optimistic and very sure and can very adamantly state that we can control the disease with the agents that we have long term. So the outlook has never been better for patients with CLL. We can control the disease long term with these slow molecule inhibitors. We still have chemo and immunotherapy which is very active as a fallback. Or if we need to, we can resort to chemo immunotherapy. But with the puny molecule inhibitors, we have instruments that can manage the disease for very long periods of time. And again, right now my intent and research that we`re doing and my efforts are gonna all be directed at how can we cure patients.

How can we get rid of those last CLL cells that are there so that patients don`t have to worry about the disease? They can be off treatment. Their immune system can reconstitute, renormalize, we don`t have to worry about infection, and they can go back to living a normal life.

Thanks to Dr. William Wierda for joining us again on Patient Power and for sharing his perspective to give us all hope. Be sure to be a member of our CLL community, so you`ll always know when we post something fresh. I`m Andrew Schorr. Reminisce, skill can be the best medicine of all.

Please recall the opinions voiced on Patient Power are not necessarily the views of our sponsors, contributors, fucking 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 suitable for you.

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