Optimizing Patient Outcomes With CAR T-Cell Therapy With Ola Oluwole, MD

At the recent American Society of Hematology (ASH) Annual Meeting, Dr. Ola Oluwole of Vanderbilt University Medical Center, sat down with Oncology Data Advisor to discuss two of his abstracts on prophylactic corticosteroid use for patients receiving axicabtagene ciloleucel and the role of cytokine release syndrome in the efficacy of chimeric antigen receptor (CAR) T-cell therapy.  

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, I’m at the ASH Annual Meeting with Dr. Oluwole, who is here to talk about his research. Thank you for being here.

Ola Oluwole, MD: Thank you.

Oncology Data Advisor: I believe you have two abstracts here. Would you like to tell us a little bit about these?

Dr. Oluwole: Yes, the first abstract I’m going to talk about is prophylactic corticosteroid use with axicabtagene ciloleucel. This is a two-year follow-up of mature data. The study was done in patients who were being treated with axicabtagene ciloleucel, also known as axi-cel. The question was whether we can improve on the safety profile of axi-cel by giving prophylactic corticosteroids.

Why is this important? Axi-cel is the first CAR T-cell therapy approved for large B-cell lymphoma. It is highly effective. Almost 90% of patients respond, but 50% may even be cured with the treatment. However, there are some toxicities that come with this, such as cytokine release syndrome, or cytokine storm, and some neurological toxicities. The question was whether we can preserve the efficacy, but at the same time, improve the safety profile. In other words, instead of giving multiple doses of corticosteroids when they develop high toxicity, why don’t we preempt that with a small dose of easily tolerable corticosteroids?

We gave corticosteroid prophylaxis on Days 0, 1, and 2. What we found was that, indeed, the efficacy was preserved. Over 95% of the patients still responded, but the toxicity profile was much safer. For example, high-grade cytokine release syndrome of grade 3 or higher was 13% in the original study, but it was 0% in our study. We also found that that grade 3 or higher neurological events were about 10 points lower. Instead of about 30%, we had about 17%. It makes us feel good that this is something that we can recommend to be able to improve the safety profile of axicabtagene ciloleucel.

Oncology Data Advisor: Great, that’s a very interesting abstract. How about your other one?

Dr. Oluwole: The other abstract I’m going to talk about is abstract 4929. This is a work that was done with the Cell Therapy Consortium, where eight academic centers decided to pull cases. The question in our study was about how when we treat patients with CAR T-cell therapy in the commercial setting, some of them develop cytokine release syndrome; most of them do, but there are some that do not.

The question is, the ones that do not have the cytokine release syndrome, are they at a disadvantage? Does it mean that this treatment is not going to work?

What we did was a retrospective analysis of about 351 patients, looking at those who developed cytokine release syndrome and those who did not, and then looking forward to see how they fared. A total of 351 patients were treated, and 74.4% developed cytokine release syndrome, while 25.5% did not. When we looked at their outcomes, those that did not have cytokine release syndrome did just as well, for the most part, as those who did.

The take-home message is that when patients don’t develop cytokine release syndrome, it doesn’t mean that nothing is happening. It may not rise to the level that we can grade cytokine release syndrome, but the treatment is still effective. We expect the treating physicians not to rely on cytokine release syndrome as a judgement stick, but to lay the treatment around its cause, obtain the scan at the time they need to obtain it, and then get objective evidence of response or no response.

Oncology Data That’s great, that’s another very interesting abstract. Thank you much for talking today. I appreciate it.

Dr. Oluwole: Thank you very much for having me.

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. Oluwole

Ola Oluwole, MD, is an Assistant Professor of Medicine and Hematology/Oncology at Vanderbilt University Medical Center in Nashville, Tennessee. He specializes in the treatment of hematologic malignancies, particularly chronic lymphocytic leukemia and Hodgkin and non-Hodgkin lymphomas. Dr. Oluwole is actively involved in clinical trials investigating targeted therapies to improve outcomes in hematologic malignancies.

For More Information

Oluwole OO, Forcade E, Muñoz J, et al (2022). Prophylactic corticosteroid use with axicabtagene ciloleucel (axi-cel) in patients (pts) with relapsed/refractory large B-cell lymphoma (R/R LBCL): 2-year follow-up of ZUMA-1 cohort 6. Presented at: American Society of Hematology Annual Meeting. Abstract 4667.

Bhaskar S, Patel V, Porter DL, et al (2022). Cytokine release syndrome (CRS) is not required for CAR-T cell efficacy in aggressive large B-NHL. Presented at: American Society of Hematology Annual Meeting. Abstract 4929.

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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