Subsequent Treatment After CAR T-Cell Therapy in Large B-Cell Lymphoma With Armin Ghobadi, MD

Recently, at the American Society of Hematology (ASH) Annual Meeting in New Orleans, Dr. Armin Ghobadi, an Associate Professor at the Washington University School of Medicine, Siteman Cancer Center, sat down with Oncology Data Advisor to enlighten us about his research and presentation regarding the ZUMA-7 trial, in which he discusses the outcomes of subsequent anti-lymphoma therapies in patients with diffuse large B-cell lymphoma (DLBCL) following treatment with axicabtagene ciloleucel.

This podcast episode was recorded live by Oncology Data Advisor and ConveyMED at the 2022 ASH Annual Meeting in New Orleans.

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we're here at the ASH Annual meeting with Dr. Armin Ghobadi from Washington University, in St. Louis. Thanks so much for being here.

Armin Ghobadi, MD: Thanks for having me here.

Oncology Data Advisor: Would you like to tell us a little bit about yourself and about your research?

Dr. Ghobadi: I'm Armin Ghobadi. I'm an Oncologist and an Associate Professor at Washington University, in Saint Louis, in the Department of Medicine and Division of Oncology. I'm a Clinical Director of the Center for Gene and Cell Immunotherapy over there. My main area of clinical translational research is cell therapy for hematologic malignancies.

Oncology Data Advisor: Great. And I believe you have a study here on the ZUMA-7 trial?

Dr. Ghobadi: Yes, so just a brief background about ZUMA-7, it was a randomized phase 3 trial to answer a specific question of what's the best second-line treatment for patients with primary refractory diffuse large B-cell lymphoma. At the time of design of the study, patients had primary refractory DLBCL relapsed within 12 months. The standard of care was getting chemotherapy followed by autologous transplant. So, the study was designed to answer the question if chimeric antigen receptor (CAR) T axicabtagene ciloleucel (axi-cel) specifically over there is better than chemo followed by autologous transplant, yes or no. And as we know, the result of that was a positive primary end point of event-free survival. Axi-cell in that setting was significantly better than chemo followed by autologous transplant. This study that we are presenting today looked at the subsequent treatment in ZUMA-7 after the second-line setting.

As an Oncologist, right now we know that based on the result of ZUMA-7, axi-cel is proven in the second-line setting. So, if the patient has a primary refractory disease or relapses within 12 months, they get axi-cel, or lisocabtagene maraleucel (liso-cel) is approved in this scenario as well. And when they get second-line setting CAR, if they don't respond or relapse within 12 months, what do you do? What's going to happen if you give them any line of therapy at that time? So, we wanted to look at that specific question. In this study, we looked at third-line treatment after axi-cel or after a standard-of-care chemo and transplant in both arms of axi-cel and transplant in ZUMA-7. And specifically, these are the main results that we had. ZUMA-7 obviously was not designed to look at the third-line setting. This is mainly descriptive, but I think informative data.

One, when you look at the second-line axi-cel arm versus when a patient gets chemo, and if they don't respond to chemo, they get CAR, the outcome of a patient that received CAR seems better when you get it earlier. Two, if the patients get axi-cel and don't respond, giving cell therapy followed by transplant still is a viable option for those patients. If the patient gets CAR in the second line and they don't respond or relapse later using a different type of chemoimmunotherapy, and if they respond, they are chemosensitive. Consolidated with the transplant, specifically autologous transplant is a viable effective option for those patients.

Oncology Data Advisor: Great. Thanks so much for sharing. Anything else you'd like to share about either your research here or the other research in this field that you've seen this weekend?

Dr. Ghobadi: There have been several interesting presentations. We have, actually, another abstract that looked at specifically how we can augment the function of CAR after CAR infusions. So, that's the poster that we looked at. Just a little bit of a background, when you give a CAR to a patient, expansion of a CAR is an important factor in term of efficacy and duration of response. So, patients who usually go to remission, or have prolonged survival, have a robust expansion of the CAR. In this study we said, "What about giving a booster to CAR-T after they get the CAR?" And basically, there's a growth factor for a T-cell—it's called interleukin-7 (IL-7)—and it is a long-acting form of NTI7. We gave that three weeks after getting a CAR to our patients and we saw a significant expansion of CAR-T after injection of that NTI7. So, it's early on, but that's promising. We're hopeful that we can bring it early on, to earlier post-CAR, and we can go higher. In term of dose, we have not seen any toxicity. The goal is helping CAR T-cells to proliferate better and expand better, and hopefully more patients go to complete response (CR) and stay in CR.

Oncology Data Advisor: Awesome. That's really exciting. Thank you for talking about this. It'll be really exciting to see how the research continues to play out in the future.

Dr. Ghobadi: All right, thank you.

Thank you for listening to this podcast. Recorded live at the 2022 ASH Annual Meeting by Oncology Data Advisor and ConveyMED. For more expert perspectives on the latest in cancer research and treatment, be sure to subscribe to the podcast at ConveyMED.io and OncData.com. Don't forget to follow us on social media for news, exclusive interviews, and more.

About Dr. Ghobadi

Armin Ghobadi, MD, is an Associate Professor of Medicine in the Division of Medical Oncology at the Washington University School of Medicine, Siteman Cancer Center, in Saint Louis, Missouri. Dr. Ghobadi's clinical research and interest lie within treating patients with leukemia and lymphoma, as well as helping those through the recovery process. He is a member of the Leukemia and Lymphoma Specialist Teams at Siteman Cancer Center as well.

For More Information

This transcript has been edited for clarity. Any views expressed above are the speaker's own and do not necessarily reflect those of i3 Health.