ASCO 2021 | ZUMA-2: outcomes of R/R MCL patients who progressed within 24 months of diagnosis
Michael L. Wang, MD, MD Anderson Cancer Center, Houston, TX, talks on outcomes of patients with relapsed/refractory (R/R) mantle cell lymphoma (MCL) with disease progression within 24 months of diagnosis (POD24) who received brexucabtagene autoleucel in the ZUMA-2 trial (NCT02601313). Prof. Wang reports that, with a median of 17 months of follow-up, patients with POD24 had more aggressive high-risk disease characteristics, with generally lower CAR-T expansion and progression-free survival in comparison to patients without POD24. Prof. Wang gives an overview of key updates from the ZUMA-2 trial, commenting on the safety profile of brexucabtagene autoleucel, and indicating a potential benefit of earlier intervention. This interview took place at the virtual European Hematology Association (EHA) Congress 2021.
Transcript (edited for clarity)
It’s my pleasure to discuss some of the presentations at the EHA and ASCO. One of the abstracts or posters we presented is the outcome of KTE-X19 in patients with relapsed/refractory mantle-cell lymphoma in ZUMA-2 who had progression of disease within 24 months of diagnosis.
So, everybody knows the first report for ZUMA-2 was at ASH 2019. At that time, the follow-up time was 15 months...
It’s my pleasure to discuss some of the presentations at the EHA and ASCO. One of the abstracts or posters we presented is the outcome of KTE-X19 in patients with relapsed/refractory mantle-cell lymphoma in ZUMA-2 who had progression of disease within 24 months of diagnosis.
So, everybody knows the first report for ZUMA-2 was at ASH 2019. At that time, the follow-up time was 15 months. Later on, the mantle cell was published that in The New England Journal of Medicine on April 1st of 2020, the follow-up time was 15 months. So later on, we presented in ASH 2020, we presented the longer follow-up data on the same trial in ZUMA-2, the follow-up time was 17.5 months median follow-up.
So, at ASCO and EHA, we presented the same data at a follow-up of median 17.5 months. However, in these two posters, in these two great meetings, we divided that according to our disease category called the progression of the disease within 24 months, so POD24. Why we studied this? Because mantle cell lymphoma after the initial therapy if the patient relapse within 24 months, so that’s a bad prognosis. We wanted to see whether this also applies to our CAR T-cell therapy.
So, we presented several figures and tables, and the conclusion is that after a median follow-up of 17 months in the KTE-X19 provided a high rate of CR in patient without the POD24 with a median duration of overall survival not reached in either group. So, to be more like that without the POD24, which means without mantle cell relapsed within 24 months, the overall response rate is 91%. The CR rate is 72%. On the other hand, if the patient relapse within 24 months, our rate was 93%. However, the CR rate is dramatically much lower, 61%. So, without a progression 72%, with the progression of 61%.
In this clinical trial, we also found that at the baseline, patients progressed within 24 months likely have high-risk of disease with high tumor burden, high IDH and a high percentage of blastoid variant in that disease category. However, the safety profiles are similar among the two groups. And also, patient with progression of within 24 months appear to have lower CAR T-cell expansion peak compared without relapse.
And we think this data suggest the earlier intervention with a CD19 CAR T-cell therapy would benefit the patient with high-risk factors. Earlier intervention means you intervene at a low tumor burden, rather than high tumor burden, you know, and also you intervene before the [inaudible] become too high. So, that’s my comment on this presentation.
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