The Evolving Role of CAR T Cell Therapy in Hematological Malignancies - Episode 1
David Maloney, MD, PhD: Chimeric antigen receptor [CAR] T lymphocyte therapy, or CAR T-cell therapy, has generated tremendous excitement, showing rapid and durable responses in patients with dismal prognoses with limited treatment options.
In this OncLive® Peer Exchange® discussion, I am joined by a panel of experts in CAR T-cell therapy research. Together, we will look at the latest data, including data from the ASH [American Society of Hematology] 2019 Annual Meeting & Exposition, to shed light on how the role of these therapies is evolving and will shape the treatment landscape over the next several years as our clinical experience grows.
I am Dr David Maloney, a member of the Clinical Research Division at the Fred Hutchinson Cancer Research Center, and the medical director of cellular immunotherapy at the Bezos Family Immunotherapy Clinic at Seattle Cancer Care Alliance in Seattle, Washington.
Today I am joined by Dr Caron Jacobson, the medical director of the Immune Effector Cell Therapy program at Dana-Farber Cancer Institute and an assistant professor of medicine at Harvard Medical School in Boston, Massachusetts; Dr Fred Locke, vice chair and associate member of the department of Blood and Marrow Transplant and Cellular Immunotherapy and the co-leader of the Moffitt immunotherapy program in Tampa, Florida; Dr Max Topp, board-certified physician in hematology and oncology at the University Hospital of Würzburg, Germany; and Dr Jason Westin, an associate professor in the Department of Lymphoma and Myeloma, division of cancer medicine, at The University of Texas MD Anderson Cancer Center in Houston, Texas.
Thank you for joining us. Let’s begin.
Today we’re going to look at the first approved CAR T-cell commercial product, which is the treatment of pediatric and young adult ALL [acute lymphoblastic leukemia]. How has the availability of CAR T-cell therapy changed the treatment landscape for patients with pediatric and young adult ALL, Fred?
Frederick Locke, MD: Full disclosure: I am not a pediatrician. I treat adults. I’m a medical oncologist. I do have 5 children, so I don’t know if that makes me an expert in CAR T-cell therapy for children. But pediatric patients who have progressed despite first-line, second-line, or third-line chemotherapy, or who have relapsed after an allogeneic transplant have historically done very poorly. These are patients who have a very low chance of prolonged disease-free survival. The approval of CAR T-cell therapy, anti-CD19 directed CAR T-cell therapy for these patients is really transformational, and it’s really affording opportunities for long-term durable responses in about half these patients who really were without other treatment options.
David Maloney, MD, PhD: I think our results are from the ELIANA study with tisagenlecleucel, which led to these really paradigm-shifting opportunities for patients with ALL. But now we’re beginning to see real-world data. What do people think about the real-world data that we’ve seen so far?
Max Topp, MD: There was a nice abstract reported on at our conference. There were 159 patients, for which the results were confirmed. A majority of patients had a great response—8% objective response rates—and there was a very high rate of MRD [minimal residual disease] negativity after treatment.
David Maloney, MD, PhD: Yeah, I think other data confirmed pretty much the results from the ELIANA trial, and around 85% to 90% of patients had MRD negativity. The majority of them were MRD-negative remissions. Obviously, the follow-up is still quite short, but I think it confirms that you can take this from a clinical trial setting into the real-world setting and do it safely. There are clearly still risks of cytokine release syndrome and neurological toxicity, which appeared similar, maybe even a little better than the clinical trial data. I think people are getting more used to dealing with these treatment options.
Caron Jacobson, MD: I just want to interject with 1 thing, which is that the number of patients who are eligible for the pediatric and young adult indication who are actually getting treated match. I think we’ll talk later about how there’s a discrepancy between eligible patients for lymphoma, but the fact that these patients are being referred and are being treated speaks to the fact that people are seeing efficacy, and that is really paradigm shifting.
David Maloney, MD, PhD: Yeah. Well, we’re all pretty much adult oncologists here. At least at our center, we’re only treating the 18-to-25-year-old range here, so there’s relatively limited experience. But in our experience, we’ve been able to give this product. There is clearly real-world experience that’s being developed.
There were some additional data presented on another CAR T-cell therapy, and the trial was called the CARPALL study. Max, do you want to say something about that?
Max Topp, MD: It’s another approach using this very exciting technology. There are some tweaks that have been made to the construct. But overall, it was a limited data set of approximately 20 patients with a very similar efficacy rate, toxicity rate. And so we just have to see if other designs in the second-generation CAR T-cell products will make a difference in the long term. But I think there are many ways of really applying this technology to this patient population.
Transcript Edited for Clarity