ASH 2024 | Five-year follow-up of the ZUMA-5 trial investigating axi-cel in R/R indolent NHL

So at this ASH 2024 meeting, we presented a five-year follow-up on the ZUMA-5 study, which is a Phase II single-arm multicenter study of axicabtagene ciloleucel, also known as axi-cel, in patients with relapsed or refractory B-cell non-Hodgkin lymphoma. That could be either follicular lymphoma or marginal zone lymphoma. So axi-cel, as you may know, is an autologous anti-CD19 CAR T-cell therapy that’s previously been approved for relapsed refractory follicular lymphoma as well as large B-cell lymphoma. And we did this ZUMA-5 study to evaluate the efficacy of axi-cel in patients with relapsed refractory indolent non-large cell lymphoma. And to be eligible, these patients had to have either grade 1 to 3a follicular lymphoma or a nodal or extranodal marginal zone lymphoma after at least two prior lines of therapy that should have included an anti-CD20 antibody and an alkylating agent. And following enrollment and leukapheresis, they received conditioning chemotherapy with cyclophosphamide and fludarabine over three days, and after two days of rest, there was a single infusion of axi-cel at a dose of 2 million CAR-positive cells per kilogram body weight. The primary endpoint for the study is overall response rate. So we now have a median follow-up of about 65 months for all enrolled patients, and there were a total of 159 patients who were enrolled, and 152 were treated. The FL cohort, we had 124 patients, and in the marginal zone lymphoma cohort, we had 28 patients. And the best overall response rate was 90%, and the best complete response rate was 75%. And within the FL cohort, we had a higher CR rate at 79%, and in marginal zone lymphoma, the CR rate was 65%. The median duration of response has not been reached, and the median PFS was 62 months, and the median time to next treatment also has not been reached. The additional analysis that we did with this five-year follow-up included lymphoma-specific survival analysis. So when we looked at lymphoma-specific PFS within the follicular lymphoma cohort, we found that there’s an emergence of a plateau after the two-year time point with only two relapses beyond month 30. And the median overall survival also has not been reached. In terms of correlative studies, we found that the peak cortisol expansion early after infusion associated with ongoing response, and patients with ongoing response had a higher peak cortisol expansion compared to those who relapsed or were non-responders. And when we looked at the product phenotype, we observed that patients who had ongoing response had a higher percentage of naive-like CAR T-cells within the product compared to those who relapsed or were non-responders. So overall, these results indicate that axi-cel appears to be a highly effective therapeutic approach for patients with relapsed or refractory indolent non-Hodgkin lymphoma. With five years of follow-up, more than half the patients remain in response without the need for additional therapy. The plateau in the lymphoma-specific PFS curve with only two relapses beyond 130 indicates to us that this therapy is potentially curative for these patients. And in terms of safety, we observed only four adverse events since the last analysis after the four-year time point. None of those were related to axi-cel. So the long-term data indicates that axi-cel does not have any late adverse events related to the study treatment. And overall, we think this is a highly effective therapeutic approach for patients with these with indolent non-Hodgkin lymphoma, and potentially curative for patients with follicular lymphoma.

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