The Future of CAR T-Cell Therapy

Currently, chimeric antigen receptor (CAR) T-cell therapy is only approved as a standard of care for refractory or relapsed patients with adult B-cell non-Hodgkin lymphoma or childhood acute lymphoblastic leukemia. However, clinical trials have begun to evaluate it as a first- or second- line of treatment. Studies are also being conducted to find CAR T-cells that may work in other forms of leukemia.

In an interview with CancerNetwork®, Mazyar Shadman, MD, MPH, discussed the study he and colleagues are conducting to evaluate CAR T-cell therapy in high-risk patients with chronic lymphocytic leukemia ahead of the 61st American Society of Hematology (ASH) Annual Meeting & Exposition, held December 7-10, 2019, in Orlando, Florida.

Q: What are you most looking forward to at ASH this year?

DR. SHADMAN: A lot of interesting studies, definitely in the lymphoma world, starting with results from specific antibody studies that will be presented, and specifically the one that we are still participating in: the CD20/CD3 bispecific antibody, mosunetuzumab. The study results will be presented as a poster at ASH; it was one of the top 6 abstracts for the whole meeting. It is a very promising drug and we are very excited to be a part of that study and we have had great responses. We are really hoping to see that drug moving forward and hopefully having it available to a lot of other patients outside of the trial after approval.

For lymphoma, we also have the CAR T-cell studies of course, in particular, the JCAR017 study coming out for large-cell lymphoma. As you know, there are 2 FDA-approved CAR T-cell therapies for diffuse large B-cell lymphoma, but JCAR017 is not currently approved for treatment. The study results that will be presented at ASH will show data which look very promising, with very similar efficacy, but probably a much better toxicity profile with CAR T-cell therapy. We are really hoping to get CAR T-cell therapy available for patients with large-cell lymphoma in the future, and that would be a very important addition to our toolbox to treat diffuse large B-cell lymphoma. So, that is another set of data to look at.

Q: Can you discuss your presentation?

DR. SHADMAN: At our institution, we have been treating patients with chronic lymphocytic leukemia (CLL) with CAR T-cell therapy in a clinical trial, so we have a lot of experience using this approach in these patients. Unfortunately, there are a significant number of patients who do not respond to CAR T-cell therapy or respond and later relapse, and so that makes it a unique patient population that are at high risk for relapse. That is a space where we need to know, first of all, the expectation, and how poorly this patient would do, because if you want to design any clinical trial to target this population you need to know the benchmark and where are you starting at so you can try to improve it. In this study, we looked at patients who had CLL and failed CAR T-cell therapy and we tried to have an understanding of their outcomes and how well or poorly they did with treatment. Also, we looked specifically at some of the characteristics that could define outcomes. This is kind of a unique study-the first in this space, retrospective, at a single institution, and a relatively small number of patients. I think this study is important, and we are already using these data to base some of the prospective trials that we are designing in this space and to make decisions in terms of the timing of referring patients for CAR T-cell therapy.

Q: Where are we in the field of CAR T-cell therapy and where do you think we are going?

DR. SHADMAN: I think we have made a lot of progress, the fact that we have 2 approved CAR T-cell therapies just for diffuse large B-cell lymphoma, it is a huge success. Right now, we are trying to get CAR T-cell therapy approved for different lymphoma histologies. The next step is to get CAR T-cell therapy available and have it as an option for patients with other types of lymphoma. That is the next line of studies, and a lot of them are already close to accrual, so this is a work in progress. The other focus is the setting in which CAR T-cell therapy is used, even for the approved currently approved indications. We first need to get the approval for other types of lymphoma. When that happens, we can try to use it in all kinds of settings, and not just refractory disease.