Nausheen Ahmed, MD, assistant professor, hematologic malignancies and cellular therapeutics, The University of Kansas Medical Center, discusses the rationale and design of a subgroup analysis of real-world outcomes with brexucabtagene autoleucel (brexu-cel; Tecartus) in patients with relapsed/refractory mantle cell lymphoma (MCL).

the FDA approved brexu-cel for patients with relapsed/refractory MCL

. This approval was supported by findings from the single-arm phase 2 ZUMA-2 trial (NCT02601313), in which, at a minimum follow-up of 6 months, the overall response rate (ORR) was 87% (95% CI, 75%-94%), including a complete response (CR) rate of 62% (95% CI, 48%-74%). At the 3-year follow-up analysis of ZUMA-2, the ORR was 91% (95% CI, 81.8%-96.7%), including a CR rate of 68% (95% CI, 55.2%-78.5%).

This noninterventional, prospective subgroup analysis included real-world patient data from the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, Ahmed says. This study evaluated long-term safety and efficacy outcomes with brexu-cel in a more diverse population of patients with relapsed/refractory MCL than what was included in the ZUMA-2 trial, Ahmed explains. Patients were stratified by the type of therapy they had received prior to brexu-cel, including BTK inhibitors, bendamustine, and autologous stem cell transplant (ASCT), as well as the number of prior lines of therapy they had received.

This study enrolled 500 patients from the CIBMTR database across 84 centers who received brexu-cel in the United States between July 2020 and December 2022, of whom 380 were eligible for inclusion in the real-world safety and efficacy analysis. At the time of the presentation of the findings from this study at the 2023 EHA Congress, some patients were still in follow-up, Ahmed notes.

The ORR with brexu-cel in this real-world study was 90%, including a 78% CR rate. In patients who had and had not previously received BTK inhibitors, the ORRs were 90% and 92%, respectively. In patients who had and had not received prior bendamustine, the ORRs were 89% and 92%, respectively. In patients who had and had not previously received ASCT, the respective ORRs were 91% and 90%.

Videos

Nausheen Ahmed, MD, discusses the rationale and design of a subgroup analysis of real-world outcomes with brexucabtagene autoleucel in patients with relapsed/refractory mantle cell lymphoma. 

Dr Ahmed on a Study of Real-World Outcomes With Brexu-Cel in Relapsed/Refractory MCL

Nausheen Ahmed, MD, assistant professor of Hematologic Malignancies and Cellular Therapeutics, the University of Kansas Medical Center, discusses the rationale for investigating real-world outcomes of patients with relapsed/refractory mantle cell lymphoma (MCL) treated with brexucabtagene autoleucel (brexu-cel; Tecartus).

FDA approved brexu-cel for adult patients with relapsed/refractory MCL

, based on findings from the phase 2 ZUMA-2 trial (NCT02601313). Accordingly, investigators launched a real-word study of patients registered in the Center for International Blood and Marrow Transplant Research database to assess real-world outcomes in patients with MCL treated with the CAR T-cell therapy. These findings were 

presented at the 2023 ASCO Annual Meeting

ZUMA-2 enrolled patients who had received treatment with prior exposure to bendamustine, an anthracycline, or a BTK inhibitor. When brexu-cel received FDA approval, it was indicated for second-line use, regardless of prior therapy, Ahmed says. However, in Europe, the indication for brexu-cel is after 2 prior lines of therapy, including a prior BTK inhibitor.

Based on these different indications and varying treatment histories for patients administered brexu-cel, investigators sought to better understand the real-world outcomes for patients treated with the CAR T-cell therapy based on the number of and types of prior treatments, she says.

Specifically, questions remain regarding if prior treatment with bendamustine could reduce the efficacy of CAR T-cell therapy, Ahmed continues. The real-world study also assessed whether the number of prior lines of therapy affects outcomes for this patient population, Ahmed concludes.

Nausheen Ahmed, MD, discusses the rationale for investigating real-world outcomes of patients with relapsed/refractory mantle cell lymphoma treated with brexucabtagene autoleucel.


Dr Ahmed on the Rationale for Investigating Real-World Outcomes of Brexu-Cel in R/R MCL

Nausheen Ahmed, MD, assistant professor, Hematologic Malignancies and Cellular Therapeutics, The University of Kansas Medical Center, discusses findings from a real-world subgroup analysis of brexucabtagene autoleucel (brexu-cel; Tecartus) in patients with relapsed/refractory mantle cell lymphoma (MCL).

In 2020, brexu-cel received FDA approval in 

adult patients with relapsed/refractory MCL

 based on findings from the phase 2 ZUMA-2 trial (NCT02601313), in which the agent elicited an overall response rate (ORR) of 91% and a complete response (CR) rate of 68% in this population, which excluded patients with no prior BTK inhibitor exposure. A prospective, noninterventional cohort study used data from 380 patients with relapsed/refractory MCL from the Center for International Blood and Marrow Transplant Research registry to determine the efficacy and safety of brexu-cel in a real-world population.

In the entire real-world study population, the ORR was 90% with a 78% CR rate, response rates that are similar to those seen in ZUMA-2, Ahmed says. The ORR and CR rates were also similar across subgroups, Ahmed notes. In patients with prior BTK inhibitors, the ORR was 90% and the CR rate was 78% vs 92% and 83% in those with no prior BTK inhibitors. In patients with prior bendamustine, the ORR was 89% and the CR rate was 76% vs 92% and 81% in those with no prior bendamustine. In patients with prior autologous stem cell transplant (ASCT), the ORR was 91% and the CR rate was 82% vs 90% and 77% in those with no prior ASCT. In addition, the CR rates were better in patients who had received fewer prior lines of therapy than in those who had received 3 or more prior lines, Ahmed emphasizes. In patients with 1 to 2 prior lines of therapy, the ORR was 94% and the CR rate was 88% vs 89% and 76% in those with at least 3 prior lines of therapy.

The estimated 12-month CR and ORR rates were 69% and 64%, respectively. The median duration of response was 21.7 months, however, the median follow-up in this study was 12.0 months at the data cutoff date, and further follow-up is necessary for more mature data, Ahmed notes. The 12-month progression-free survival rate was 61% and the 12-month overall survival rate was 74%.

This study also investigated the cumulative incidence of relapse and the risk of non-relapse mortality in the real-world population and found that at 12 months, 31% of patients had relapsed, with a median time to relapse or progressive disease of 24.0 months.

A multivariate analysis showed that when the efficacy outcomes were adjusted by subgroup, the CR rates were higher in patients who had received 1 to 2 prior lines of therapy compared with those who had received 3 or more prior lines, with an odds ratio of 2.10, Ahmed concludes.

Nausheen Ahmed, MD, discusses findings from a real-world subgroup analysis of brexucabtagene autoleucel in patients with relapsed/refractory mantle cell lymphoma. 

Nausheen Ahmed, MD

Articles

Dr Ahmed on a Study of Real-World Outcomes With Brexu-Cel in Relapsed/Refractory MCL

Dr Ahmed on the Rationale for Investigating Real-World Outcomes of Brexu-Cel in R/R MCL

Dr Ahmed on Real-World Findings With Brexu-Cel in MCL