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Real-World Outcomes of Brexucabtagene Autoleucel for Mantle Cell Lymphoma With Swetha Kambhampati, MD

At the recent American Society of Hematology (ASH) Annual Meeting, Swetha Kambhampati, an Assistant Professor in the Division of Lymphoma at City of Hope, sat down with Oncology Data Advisor to further discuss her presentationregarding real-world outcomes of brexucabtagene autoleucel (brexu-cel) in patients with relapsed/refractory mantle cell lymphoma.  

Oncology Data Advisor: Welcome to Oncology Data Advisor. Thank you so much for being here with us today. Would you like to begin with introducing yourself and your research interest?

Swetha Kambhampati, MD: I'm Swetha Kambhampati. I'm an Assistant Professor at City of Hope. My research interests are in B-cell non-Hodgkin lymphoma, diffuse large B cell lymphoma (DLBCL), follicular, mantle, and I do some work in Hodgkin as well. I'm a Clinical Investigator and interested in looking at real-world outcomes of therapies as well as developing novel therapies for patients.

Oncology Data Advisor: Thank you again for your time today. We really appreciate it. First question I wanted to ask you is if you could give us an overview of your abstract and presentation.

Dr. Kambhampati: Absolutely. I presented at this year's ASH the largest real-world study to date evaluating outcomes of brexu-cel in relapsed/refractory mantle cell lymphoma. It specifically looked at patients with high-risk features, namely deletion TP53 or 17p, high Ki-67 using a cutoff of 50%, and patients who would've been otherwise ineligible for the ZUMA-2 study mainly due to clinical comorbidities, performance status, and underlying cytopenias, among others.

In this abstract we demonstrated that in the overall population, the response rates and survival with brexu-cel were very comparable to that from the pivotal ZUMA-2 study. Specifically regarding the high-risk patients with TP53 deletion, we did see a numerically higher overall survival in patients without TP53 deletion, but this was not statistically significantly different. When adjusting for other variables and baseline characteristics and covariates, this remained not clinically and statistically significantly different. Outcomes were overall consistent regardless of TP53 deletion as well as high Ki-67 score.

It's important to note that we only captured TP53 deletions in this database and not TP53 mutations, as this was not available to us in the Center for International Blood & Marrow Transplant Research® (CIBMTR®) database. This is something that needs to be further explored in the future.

In terms of safety, the real-world outcomes were also very comparable to that of the ZUMA-2 study, including high-grade cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS), cytopenias, and infections. We did see in looking at the impact of high-risk features on safety, there was in the multivariate adjustment model an increased risk of prolonged cytopenias, thrombocytopenia, neutropenia, and post–chimeric antigen receptor (CAR)–T cell therapy in patients with TP53 deletion. But other safety outcomes of interest were all comparable.

Oncology Data Advisor: How is brexu-cel unique in this high-risk characteristic setting?

Dr. Kambhampati: Historically, patients with TP53 deletion, high Ki-67, and or Mantle Cell Lymphoma International Prognostic Index (MIPI), these patients with complex karyotypes have very poor prognosis. In particular TP53 deletion patients have a median progression-free survival (PFS) less than one year and overall survival less than two years. Data has shown that traditional therapies like frontline chemoimmunotherapy and autologous stem cell transplant still have very dire outcomes in these high-risk patients. I think we need novel treatment options, and brexu-cel is currently the only FDA-approved CAR-T product for relapsed/refractory mantle cell lymphoma. We've already demonstrated that patients who received brexu-cel in our real-world study that was presented previously at the American Society of Clinical Oncology (ASCO), when they received it in earlier lines of therapy, there were higher complete response (CR) rates than those who were more heavily pretreated, which is not surprising considering their T cells were probably more fit and less exhausted.

I think it is important with this data that we see that we potentially in the future use CAR-T as earlier lines of therapy, particularly in these high-risk patients where there are very limited treatment options and poor prognosis with other standard therapies.

Oncology Data Advisor: I know you began to touch on it, but if you wouldn't mind me asking, what were a bit of the limitations you experienced with this study that you would like to address in the future?

Dr. Kambhampati: Yes, there are definitely limitations. This was a prospective cohort study using the CIBMTR registry database, but just like other registry studies, there are missing data. It's a short follow-up of about a median of 12.3 months. Primarily, there's missing granularity on cytogenetics, whether there's a P53 level of expression, MIPI, a diagnosis, and TP53 aberrations and mutations as again, we only capture TP53 deletions and there are prognostic differences between TP53 deletion and TP53 mutation. I think those are important limitations. We need to further explore the outcomes with the longer follow-up and with additional data sets capturing these additional pieces of information.

Oncology Data Advisor: Definitely. I know you also touched on your next steps already, but if you could give us a glimpse into the next year of what to look forward to from your team in this area?

Dr. Kambhampati: Yes, I think in this next year we're going to—we've kind of looked at brexu-cel real-world data overall and by prior treatment and now with high-risk features. I think for the future going forward, longer follow-up is the key in sort of looking at these data sets. There have been other consortium studies looking at this as well, but continuing to look with large sample size outcomes in the real-world setting with additional data that's captured, given some of the missing limitations that I mentioned already, I think is what to expect in the future. Obviously, eventually looking at an ongoing process in the real-world setting in these patients with high-risk features and limited treatment options, particularly in the earlier lines, would be good.

Oncology Data Advisor: We look forward to hearing about the updates in the next year or two, so thank you so much.

Dr. Kambhampati: Great. Thank you so much. Really appreciate it.

About Dr. Kambhampati

Swetha Kambhampati, MD, is an Assistant Professor in the Division of Lymphoma in the Department of Hematology & Hematopoietic Cell Transplantation at City of Hope. Dr. Kambhampati's research interest and passion is in lymphomas where she is an active participant in clinical trials. As well, with her combined passion for science and health, she advocates for compassionate and personalized care for all patients.

For More Information

Kambhampati S, Ahmed N, Hamadani M, et al (2023). Real-world outcomes of brexucabtagene autoleucel (brexu-cel) for relapsed or refractory (R/R) mantle cell lymphoma (MCL): a CIBMTR subgroup analysis of high-risk characteristics. Presented at: 2023 American Society of Hematology Annual Meeting. Abstract 107. Available at: https://ash.confex.com/ash/2023/webprogram/Paper179269.html

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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