At the 2023 American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Illinois, Swetha Kambhampati, MD, City of Hope National Medical Center, Duarte, California,  presented data on the real-world outcomes of brexucabtagene autoleucel treatment for patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL). 

The results of this study, conducted through a subgroup analysis of outcomes based on prior treatment, confirm the consistent safety and efficacy of brexucabtagene autoleucel therapy in the real-world setting, regardless of patients’ previous therapeutic regimens. 

Transcript:

Hi, I'm Swetha Kambhampati. I'm an assistant professor at City of Hope and I'm here at ASCO 2023. I'm excited to present the results of the brexucabtagene autoleucel (brexu-cel) real-world [Center for International Blood and Marrow Transplant Research] (CIBMTR) study, looking at outcomes based on prior treatment.

This is the largest real-world study looking at brexu-cel in mantle cell lymphoma, a relapsed/refractory disease. It's always important to look at the safety and efficacy of therapies in the real-world setting as clinical trials can be very selective in their eligibility criteria. The pivotal trial that led to the approval of brexucabtagene was the ZUMA-2 study. In this study, we look at data from the CIBMTR registry and evaluate the real-world safety and efficacy of this therapy.

In this study, we included 380 patients. It was a prospective, non-interventional cohort study across 84 centers in the United States, from July 2020 to December 2022. In these 380 patients, we had a very real-world clinical situation: a high-risk patient population. The median prior lines of treatment were 4 and ranged from 1 to 12. 20% had TP53 deletion and 44% had high Ki-67. This consisted of high-risk patients, some of whom may not have been eligible for ZUMA-2 based on their eligibility criteria. In this study, with a median follow-up of 12 months, we observed an overall response rate of 90% and a CR rate of 78%. These results are actually very comparable to that reported in ZUMA-2. The median duration of response was 21.7 months.

With respect to safety, we observed any grade [cytokine release syndrome] (CRS) in 88% of patients and any grade [immune effector cell associated neurotoxicity] (ICANS) in 60% of patients. High grade was seen in 10 and 28% of patients, respectively. Again, [this was] pretty comparable to that reported in ZUMA-2. Other toxicities we observed [were] about 21% of patients with prolonged thrombocytopenias, 6% subsequent neoplasms, and 41% clinically significant infections.

One of the unique things about the study is that we looked at outcomes based on prior treatment, including exposure to [Bruton’s tyrosine kinase] (BTK) inhibitor, autologous stem cell transplant, bendamustine, and prior lines of therapy. This is important because, in the ZUMA-2 study, patients who were BTK-naive are not eligible for enrollment. In real-world practice, the FDA label does not specify prior treatment, so this leads to different heterogeneity in clinical practices. The impact of prior bendamustine is also an important question that's come up for patients who are treated with [chimeric antigen receptor] (CAR) T.

When looking at these outcomes by prior treatment using multivariate analysis, we found that prior BTK inhibitor exposure and bendamustine did not statistically significantly affect the response rates or the survival outcomes. Patients who had received prior transplants did have improved [progression-free survival] (PFS). In terms of safety, we found that patients who had received prior bendamustine had prolonged thrombocytopenia and reduced risk of grade 3 or higher ICANS. We also noted that patients who received treatment in earlier lines of therapy, 1 to 2 prior lines, had higher response rates and had two-fold higher odds of achieving a [complete response] (CR), potentially suggesting earlier use of CAR T therapy in patients.

[It] is important to note that our follow-up was 12 months, so future research would involve looking at longer follow-up of these patients, larger sample sizes in some of the subgroup analysis cohorts, as well as getting more granular details. This study overall, in the largest sample size we have so far, shows the safety and efficacy of this treatment in the real-world setting for patients with relapsed refractory mantle cell lymphoma.

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 by prior treatment. Presented at the ASCO Annual Meeting; June 2-6, 2023; Chicago, Illinois. Abstract 7507