Management of Chronic Lymphocytic Leukemia in 2020 - Episode 18

CAR T-Cell Therapy for Relapsed/Refractory CLL


William Wierda, MD, PhD: The other exciting area of study, not only in CLL [chronic lymphocytic leukemia] but in other lymphomas is the CAR [chimeric antigen receptor] T-cell work. Tanya Siddiqi, MD, presented an update the of TRANSCEND study, which is the JCAR017 construct in patients with chronic lymphocytic leukemia. You were chairing that session. I wonder if you could give us a summary of that experience and where we think we’re going with CAR T therapy for CLL.

Shuo Ma, MD, PhD: Yes. I think CAR T is probably the next most exciting arena for CLL therapy. As we know, CAR T stands for chimeric antigen receptor T-cell therapy; so CART-19 has been FDA approved for 2 indications, for relapsed/refractory diffuse large B-cell lymphoma as well as for pediatric ALL [acute lymphocytic leukemia] patients. For CLL…the first report of successful treatment with CAR T was in CLL, but after that there were several years where the research has not been pushed ahead, probably because we have so many other good therapies for CLL.

But now this one is a very exciting report of using the CAR T treatment, the Juno Therapeutics product, which is using a CD4, CD8, 1:1 ratio mixing of the T cells, which distinguishes it from the other CAR T products. In this setting, they’re using for patients who have, if they have standard-risk feature, they have to have at least 3 prior lines of therapy. If they have high-risk features, then they have to have at least 2 prior lines of therapy. And they all have to have prior exposure to ibrutinib, either being intolerant or resistant to ibrutinib.

So, even among this heavy pretreated group of patients, the response is pretty exciting. It seemed to be overall response close to 80% and the complete response in the 45% range. Some of the patients can actually have a fairly durable response. Considering that in the era of targeted therapy, we always think what are we going to do for patients who are failing the BTK [Bruton tyrosine kinase] inhibitor as well as the venetoclax, what options do patients have?

I really think CAR T might be the best option. Of course, we’re always concerned about the potential toxicity associated with the CAR T, primarily cytokine release syndrome and neurotoxicity. Cytokine release syndrome is fairly common in this particular clinical trial as well. However, the more severe cytokine release syndrome is actually less than 10%, so that’s also very encouraging. The neurotoxicity also is manageable. I think we’re learning a lot more about how to have an early start of steroids that can potentially reduce the chance of severe neurotoxicity. So, even though there are still some toxicity concerns, I do think efficacy wise, for patients who are failing the standard targeted therapy, CAR T might be their best option.

Transcript Edited for Clarity