Published on October 2, 2020
Novel CLL Treatment Advances
Where do treatment advances like stem cell transplant and CAR T-Cell therapy fit in for chronic lymphocytic leukemia (CLL) patients? Are CLL experts hopeful for a cure? Dr. Paul Barr of the University of Rochester Wilmot Cancer Center discusses with host and CLL patient himself, Andrew Schorr. Watch to hear what treatment options Dr. Barr calls "curative" and what he is excited about.
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Transcript | What Advances Have Been Made In CLL Treatment?
What’s the latest on CAR T-cell therapy?
Two different CAR T products are approved for diffuse large B-cell lymphoma. Another was just recently approved for mantle cell lymphoma and the investigations are ongoing in CLL. So because of the very good outcomes in the more aggressive diseases, we are anxious to learn more about more aggressive forms of CLL those outcomes. To date, while in diffuse large B-cell lymphoma, for example, we've seen lasting remissions in about 40% of patients in the CLL patients who have failed some of the treatments, or I should say the treatments have failed the patients - the therapies that we were previously talking about. We're seeing remissions more like in the 25% range, a quarter of patients will have lasting remissions.
So, we still have a ways to go. We need to better understand when to apply these therapies, how to improve the outcomes and knowing that there can be significant toxicity, CAR T-cell therapy isn't always applicable to all of our older patients. So, gives you an idea of some of the struggles we're having with CAR T-cell therapy but nonetheless, I still think it is worthy of further study for sure.
So, CAR T is a drug personalized to you. So I think there's one thing going on. Let's talk about, is there a sort of an off the shelf CAR T. In other words, will there be improvements or refinements that might lower costs, lower toxicity, I mean, is it an evolving field where it might apply to more people?
Yeah. So there are many different efforts trying to improve upon the CAR T strategy. Think of making CAR T products from another patient's T-cells, allogeneic chimeric antigen T-cell receptor therapy. That strategy cuts down on the time processing the T-cells and might enable us to have a product that we can take from the shelf and administer to a patient with other allogeneic products. Other situations can arise graft versus host disease could in theory occur from such a product.
So those sorts of studies are very early on and very few CLL patients have received the off the shelf type products. So, long way to go but again, as you pointed out, the hope is that we can have something readily available rather than having to process a patient's own cells, send them off to the lab, have them come back and put them through this whole process.
Stem Cell Transplants and CLL
So, Dr. Barr, if you go back over the years, there are some patients who've had stem cell transplant. Allogeneic transplant for CLL and I've heard you even mention - not too often now. Where do we stand with that? Because that's truly immunotherapy, you're rebooting your immune system with somebody else's cells.
Agreed. I describe it to patients as getting a new immune system to hopefully fight off the cancer, to truly eradicate the disease. It's the one therapy that can be curative. The reason it’s used somewhat as a last resort is that as we've been talking about some of these more aggressive therapies can be associated with severe, and sometimes life-ending side effects. The ones we dread with stem cell transplantation include graft versus host disease. Which is akin to the new immune system attacking the patient's body or severe infections as we're suppressing the native immune system. I'd say we still think of stem cell transplantation in our patients that have failed the standard therapies when the disease really has progressed through BTK inhibitors, venetoclax (Venclexta) and even further lines of therapy acknowledging that if we can get a patient still at a deep enough remission, there can be time to use a stem cell transplant and occasionally cure the disease.
I am excited about some of the novel strategies given the progress we've made so far and seeing individual patients receive some of the newer treatments. Whereas a few years ago they wouldn't have had anything that had a significant chance of prolonging their life to see patients go into deep remissions and get back to normal quality of life is very encouraging. So I'm still very excited about combining the novel agents like our... I told you about our combination studies. There's many of those going on. The CAR T-cell products I think could change how we treat patients with high-risk molecular features. And there's even novel agents that we haven't talked about. A good example are the non-covalent BTK inhibitors that may allow us to treat patients with a BTK inhibitor once they've failed the standard ones, like ibrutinib (Imbruvica), acalabrutinib (Calquence) or zanubrutinib (Brukinsa) to have newer and better treatments and to see patients respond and thrive is obviously very exciting.