iwCLL 2023 | Results from the US Lymphoma CAR-T consortium on brexu-cel for R/R MCL in SoC practice
In this video, Yucai Wang, MD, PhD, Mayo Clinic, Rochester, MN, summarizes the findings of the US Lymphoma CAR-T consortium on brexucabtagene autoleucel (brexu-cel) for treatment of relapsed/refractory (R/R) mantle cell lymphoma (MCL) in standard-of-care (SoC) practice. Brexu-cel was approved for the treatment of R/R MCL based on the Phase II ZUMA-2 trial (NCT02601313), however many patients in the SoC setting would not have been eligible for this trial. Hence, the consortium addressed the question of whether brexu-cel would confer similar efficacy in SoC practice. Dr Wang also addresses which groups of patients may experience worse treatment outcomes. This interview was recorded at the biennial International Workshop on Chronic Lymphocytic Leukemia (iwCLL) 2023 meeting, held in Boston, MA.
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Transcript (edited for clarity)
So the brexu-cel is a CD19 targeting CAR T-cell therapy that has been approved for relapsed refractory mantle cell lymphoma in the US and many other countries. The US Lymphoma Consortium wanted to address the question whether patients treated in a standard of care practice will see similar efficacy compared with those patients who were treated in the pivotal trial. The reason being that, in the standard of care practice, many patients have a lot of comorbidities that would have made them ineligible for trials...
So the brexu-cel is a CD19 targeting CAR T-cell therapy that has been approved for relapsed refractory mantle cell lymphoma in the US and many other countries. The US Lymphoma Consortium wanted to address the question whether patients treated in a standard of care practice will see similar efficacy compared with those patients who were treated in the pivotal trial. The reason being that, in the standard of care practice, many patients have a lot of comorbidities that would have made them ineligible for trials. In other words, the standard care practice patient population may be different than those treated in trial population.
So this is a collaboration in the consortium involving 16 centers. In the end, we have 168 patients that were treated with brexu-cel in the standard of care practice setting for relapsed mantle cell lymphoma. And what we observed, in terms of efficacy, was that the response rate and CR rate were very similar to the pivotal ZUMA-2 data, and also in terms of early follow-up progression free survival and overall survival, the efficacy data were also very similar to the ZUMA-2 pivotal trial data. What’s interesting is if you look at patient eligibility for ZUMA-2, those who would have been ineligible for ZUMA-2 were the majority of the study population, up to 70-80%. Despite that, these patients still benefited similarly to the trial population.
In terms of side effects, the rate of cytokine release syndrome and neurotoxicity were again similar to the ZUMA-2 data. We do have cytopenia and infection data and non-relapsed mortality data that were described in more details in the paper.
Then one interesting observation from this study is that the high risk features, unfortunately, still predict a worse outcome, such as Tp53 mutation, high MIPI score, and complex karyotype. So those patient populations remain an unmet need in our practice. The other interesting finding is that recent exposure to bendamustine seemed to impact the treatment outcome negatively. So that may have implications in how we choose treatment in the availability of CAR-T for some patients with relapsed disease.
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