At the 65th ASH Annual Meeting in San Diego, California, Swetha Kambhampati, MD, City of Hope National Medical Center, Duarte, California, shared analysis of  real-world outcomes among patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL), including high-risk subgroups, such as those with deletion of TP53 or 17p, and Ki-67 PI, who received brexucabtagene autoleucel as treatment.

The data showed this treatment yielded efficacious results consistent with prior finding, supporting brexucabtagene autoleucel as the standard of care for patients with R/R MCL, including with high-risk features.

Transcript:

Hi everyone, I'm Swetha Kambhampati from City of Hope, and I'm here at ASH 2023. At this year's ASH, I presented data on real-world outcomes of brexucabtagene autoleucel in relapsed/refractory mantle cell lymphoma. 

This was a CIBMTR study and specifically looked at outcomes in the real-world setting for patients with high-risk features, namely TP53 deletion or 17p deletion high KI-67 score over 50% and patients [who] would otherwise be ineligible for ZUMA-2 study. In this real-world study across 83 centers in the United States, we found that the overall response rates were very comparable to the pivotal ZUMA-2 trial. So was this safety, including high-grade [cytokine release syndrome] (CRS) and [immune effector cell-associated neurotoxicity syndrome] (ICANS) specifically when looking at patients with high-risk disease features. We found that there was a numerically higher overall survival in patients without TP53 deletion, but this was not statistically significantly different. 

When in our multivariate model adjusting for other cohorts and baseline characteristics, we found that response rates and survival and duration of response [were] very comparable in patients, regardless of TP53 deletion status as well as Ki-67 over 50%. With respect to safety, we also found very comparable rates of high-grade CRS and ICANS across the high-risk subgroups. There was a numerically high rate of high-grade ICANS as well as prolonged cytopenias in patients with TP53 deletion. 

In our multivariate model, we found that the only statistically significant difference in safety was prolonged cytopenias in the TP53 deletion group. Other safety outcomes of interest, including CRS, ICANS, infections, and non-relapse mortality [were] overall comparable between the high-risk subgroups. In summary, this is an important real-world study looking at specifically high-risk disease patients. 

We all know these patients have a very poor prognosis with limited treatment options. In this study, we find that overall, they're very comparable efficacy and safety outcomes in this group. But there are some important limitations of this real-world study, including the fact that in this dataset, we only capture TP53 deletion and not TP53 mutations, which do have different prognostic impacts. Going forward, we need longer follow-up for these patients as well as evaluating other things like complex karyotype and cytogenetics and TP53 mutations and aberrations and outcomes of [brexucabtagene autoleucel] in these high-risk patients. Thank you.
 

Source: 

Kambhampati S, Ahmed N, Hamadani M, et al. 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 the ASH 65th Annual Meeting & Exposition; December 9-12 2023; San Diego, California. Abstract 107