Optimizing Systemic Therapy for Chronic Lymphocytic Leukemia - Episode 13

CAR T-Cell Therapy for CLL


William G. Wierda, MD, PhD: let’s talk a little bit about CAR [chimeric antigen receptor] T-cell therapy, and Alexey, you can give your thoughts on, there were 3 abstracts presented with regard to CD19 CAR T-cell therapy in CLL [chronic lymphocytic leukemia]. Maybe you can tell us about what those were and how those are different than prior data that had been presented.

Alexey V. Danilov, MD, PhD: There were 3 abstracts. The population in those abstracts is still very small, so it’s still very early data with CLL and CAR T-cell therapy. The University of Pennsylvania data focused on about 20 patients, as far as I recall, and those patients first received ibrutinib and then went on to receive CAR T-cell therapy. And there were responses, deep responses to CAR T-cell therapies, not among all patients, but as far as I remember, maybe 30% or 40%. However, there were also significant toxicities. Again, the cytokine release syndrome was fairly prevalent. The neurologic toxicities were there. There was 1 death on the study, which is, I would say, very significant in this small subset of patients. Therefore, to me, this is still very early data and [they don’t] clarify to me necessarily how to use CAR T cells in CLL. And I wouldn’t necessarily think that this would be the approach to use in patients after several months on ibrutinib to try to deepen the response. The data from City of Hope focused on about 10 patients, and there were several complete responses, but, again, it’s a very small subset of patients. I think it’s really still very early days in the CAR T-cell therapy in CLL.

Matthew S. Davids, MD, MMSc: It seems to me that CAR T cells on their own in CLL have not made as much of an inroad as compared to, say, DLBCL [diffuse large B-cell lymphoma] or ALL [acute lymphoblastic leukemia], probably due to this immune dysfunction inherent to CLL. To me the takeaway from the ASH [American Society of Hematology] abstracts this year [2018] was by using ibrutinib, that may have an immune stimulating effect and may enhance the activity of the CAR T cells. But again, I agree with Alexey, the numbers are small, but I think it looks promising that ibrutinib is actually helping to deepen responses in more patients.

Alexey V. Danilov, MD, PhD: I think in this era of choice of several targeted therapies, BCL2 inhibitors, PI3K [PI3-kinase] inhibitors, BTK [Bruton tyrosine kinase] inhibitors, noncovalent BTK inhibitors … it’s not immediately on my mind for my patients.

Anthony R. Mato, MD: I also agree with the point you made about toxicity and inclusion criteria. I think for all of these trials, we have to look really closely at who are allowed to receive CAR T, and whether or not if we were seeing these patients in the office, we would think they needed any further therapy whatsoever. Six months of ibrutinib and a PR [partial response] to me is a success. In fact, that’s every single patient, so I think that’s an important thing to keep in mind.

Matthew S. Davids, MD, MMSc: Although, if that patient is younger and has clear 17p deletion, TP53 mutation, I think being aggressive, at least in the clinical trial setting, and studying combination approaches maybe with CAR T is a reasonable approach.

Anthony R. Mato, MD: I totally agree, but those aren’t the inclusion criteria.

Matthew S. Davids, MD, MMSc: Right, yes.

William G. Wierda, MD, PhD: For sure, I agree with what you’re saying. The inclusion criteria need to be appropriate for the risk. Today, we have so many oral agents, and patients are able to maintain their normal life with treatment. So patients are doing well. It’s difficult, in my mind, to justify taking somebody who is not a high-risk patient and giving them a treatment that can put them into the ICU [intensive care unit]. But I also echo the sort of interest in perhaps there’s an increase in complete remission rate with the combination, but we need to see a little bit more data.

I also was struck by the discussion of response and looking at response by the iwCLL [International Workshop on Chronic Lymphocytic Leukemia] criteria where it appears that for these patients, there may be a little bit more what’s measured as nodal disease, so some residual lymphadenopathy by CT [computed tomography] scan where we’re seeing very deep remissions in patients who are MRD [minimal residual disease]-negative in the bone marrow. So sorting out this issue of nodal measurements and response assessments, I think is something that we really need to focus on moving forward, particularly for our clinical trials.

Transcript Edited for Clarity