Exploring the Primary Overall Survival Results of Axicabtagene Ciloleucel in the ZUMA-7 Trial With Jason Westin, MD

At the recent 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Dr. Jason Westin, Director of Lymphoma Clinical Research at MD Anderson Cancer Center, presented the primary overall survival analysis of the phase 3 ZUMA-7 trial investigating axicabtagene ciloleucel for relapsed/refractory large B-cell lymphomas. In this interview, he shares more with Oncology Data Advisor regarding the efficacy, safety, and future directions of this promising agent. 

Oncology Data Advisor: Welcome to Oncology Data Advisor. Today, we’re here at the ASCO Annual Meeting, and I’m joined by Dr. Jason Westin. Thank you so much for coming on today.

Jason Westin, MD: I’m happy to be here. Thanks for having me.

Oncology Data Advisor: Would you like to introduce yourself and share what your work focuses on?

Dr. Westin: Of course. I’m Dr. Jason Westin from MD Anderson Cancer Center in Houston, Texas. I’m the Director of Lymphoma Clinical Research and the Section Chief for Aggressive Lymphomas. My treatment focus in clinical research is largely on improving outcomes with new drugs and new therapies for patients with lymphoma.

Oncology Data Advisor: Great. So, you’re presenting results from the ZUMA-7 trial here. What is this trial investigating?

Dr. Westin: The ZUMA-7 clinical trial is a randomized global phase 3 study looking at second-line treatment for patients with refractory or early relapsed diffuse large B-cell lymphoma. The trial compared patients who received the old standard of care, which was chemotherapy, and if patients responded, to then receive high-dose therapy and autologous transplant versus a new treatment option, which is called a chimeric antigen receptor (CAR) T-cell therapy. CAR T cells are using the patient’s own immune cells, weaponizing them, and then returning them back into the patients to now seek and destroy the cancer.

The specific CAR T cell on this clinical trial is called axicabtagene ciloleucel (axi-cel). It targets CD-19, which is a common antigen on the surface of the tumor cells. This study randomized patients 1:1 to receive axi-cel or standard of care. The primary end point of the study was reported last year. It showed a statistically significant improvement in event-free survival favoring axi-cel over the old standard of care. At the ASCO 2023 meeting, we’re presenting an update now looking at the primary analysis for overall survival, where we’re pleased to announce that there is a statistically significant improvement in overall survival now favoring axi-cel. We’re reporting this as more patients are living longer with receiving axi-cel as a second-line treatment.

Oncology Data Advisor: That’s very exciting. What were the specific overall survival results that you’re presenting?

Dr. Westin: The specific overall survival results for the ZUMA-7 trial’s primary analysis for overall survival show a hazard ratio of 0.726, which translates to a reduction in risk of death of 27% for patients receiving axi-cel as opposed to the standard of care. That’s very impressive to help cure more people, but it’s also impressive in that many patients on the standard arm ultimately received a CAR T-cell therapy. They didn’t respond to or didn’t benefit from the treatment they were assigned to on the clinical trial; they came off the study and then got a third-line cell therapy. With 57% of the standard arm receiving a subsequent cellular immunotherapy, we still were able to show an overall survival advantage. In my mind, this effectively and conclusively establishes that the old standard of trying chemo first and saving CAR T-cell for the third-line is an inferior approach, and that CAR T-cell therapy—and from this trial, specifically axi-cel—should be considered a second-line treatment option.

Oncology Data Advisor: Very exciting. Were there any notable toxicities with axi-cel?

Dr. Westin: Axi-cel is a very active treatment, and it has great response rates, but it also does have toxicities. On the ZUMA-7 clinical trial, the toxicity profile of axi-cel was as expected from previous studies with CAR T-cell therapy and largely lined up for what was seen in patients in the third-line. The main side effects that people worry about for CAR T-cell therapy include cytokine release syndrome and neurologic toxicities. On this study, cytokine release syndrome was very common, but thankfully grade 3 or greater cytokine release syndrome was quite rare at only 6% of patients. The side effects were basically what we would expect for axi-cel and were largely manageable and reversible.

Oncology Data Advisor: That’s good to know. Are there any further directions or additional analyses underway as the trial progresses?

Dr. Westin: The ZUMA-7 clinical trial continues to have long-term follow-up, and I’m sure we’ll see additional follow-up analysis presented. This is the final analysis of overall survival, so the main end points that the study was looking at—event-free survival being the primary analysis, with the key secondary end points of overall response rate and overall survival—those are all finished now. So, now we’ll see long-term follow-up.

But what I would highlight from our analysis we’re presenting here at ASCO 2023 is that the curves in terms of survival and event-free survival and progression-free survival are all very stable at this time point. We’re now having a median follow-up of 47 months, so additional follow-up is not likely to show any changes in the outcomes. I think that we’ve seen that we are having a higher cure rate with axi-cel over standard of care in further analyses. I don’t think we’ll change that in terms of future directions for this product, for axi-cel.

We’re also here presenting a trial in progress poster for the ZUMA-23 study, and this is a study in frontline patients. Axi-cel is an indication in the second line or in the third line; this is now looking at frontline patients, newly diagnosed patients with large B-cell lymphoma who have high-risk features. It’s randomizing patients to receive axi-cel or to receive the standard of care of six cycles of chemotherapy. That’s something that we’ll be looking forward to seeing results in the coming years.

Oncology Data Advisor: Great. Well, thanks so much for talking about this today.

Dr. Westin: Yes, thanks for having me.

About Dr. Westin

Jason Westin, MD, is Director of the Lymphoma Clinical Research Program and Section Chief of the Aggressive Lymphoma Research Team and the University of Texas MD Anderson Cancer Center. He specializes in the treatment of patients with lymphoma, including diffuse large B-cell lymphoma, and his research focuses on designing and implementing clinical trials investigating the development of new therapies for hematologic malignancies.

For More Information

Westin J, Oluwole O, Kersten MJ, et al (2023). Primary overall survival analysis of the phase 3 randomized ZUMA‑7 study of axicabtagene ciloleucel versus standard‑of‑care therapy in relapsed/refractory large B-cell lymphoma. J Clin Oncol (ASCO Annual Meeting Abstracts), 41(suppl_17). Abstract LBA107. DOI:10.1200/JCO.2023.41.17_suppl.LBA107

Westin J, Jacobson CA, Chavez JC, et al (2023). ZUMA-23: A global, phase 3, randomized controlled study of axicabtagene ciloleucel versus standard of care as first-line therapy in patients with high-risk large B-cell lymphoma. J Clin Oncol (ASCO Annual Meeting Abstracts), 41(suppl_17). Abstract TPS7578. DOI:10.1200/JCO.2023.41.16_suppl.TPS7578

Transcript edited for clarity. Any views expressed above are the speaker’s own and do not necessarily reflect those of Oncology Data Advisor. 

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