BSH 2022 | Updates from ZUMA-7: axi-cel for R/R DLBCL

ZUMA-7 is a Phase III randomized study, which has compared axi-cel, which is a CD19-targeting CAR-T therapy, which standard of care immunochemotherapy and autologous stem cell transplant. Current standard of care in second-line treatment for transplant-eligible patients with relapsed/refractory large B-cell lymphoma is two to three cycles of salvage chemoimmunotherapy. And for patients who have chemo-sensitive disease, they are going to have an autologous stem cell transplant as consolidation.

With this strategy, outcomes, generally, what we find is around maybe 50% of patients will have a response in chemo-sensitive disease, and a proportion of them will have an autologous stem cell transplant. And around roughly half of patients who have autologous stem cell transplant are cured of their lymphoma. In the R-CHOP era, especially for patients who are either primary refractory or relapse within less than 12 months of their frontline chemotherapy, outcomes with this strategy have been rather suboptimal and the overall chances of long-term survival are less than 20% in this group.

So, in the ZUMA-7 study, this approach was compared with CAR-T cell therapy, using axicabtagene ciloleucel. Patients were randomized 1:1 between the two arms, and those allocated to the axi-cel arm went on to receive axi-cel as the definitive therapy, and patients entered into the standard of care arm received chemoimmunotherapy, and if they had a response, received autologous stem cell transplant. The results of the study have shown a significant improvement in event-free survival for patients receiving axi-cel, with the 2-year EFS in the axi-cel arm being around 40% and in the standard of care arm was around 16%. And, similarly, we have seen a significant improvement in progression-free survival for the axi-cel arm, with 46% PFS at 2 years, compared to around 27% in the standard of care therapy arm. So, 94% of patients randomized to axi-cel arm received axi-cel infusion, whereas in the standard of care therapy arm, 50% of patients had a chemo-sensitive disease and only around 35% of patients actually received an autologous stem cell transplant.

Currently, we have interim analysis on overall survival and there is a trend to improvement with axi-cel, but this has not reached statistical significance yet. We are waiting for the final overall survival analysis, which will be done in due course of time. This now represents an important step. It is an important treatment option that is hopefully going to be available for our patients going forward. We’ve now heard that axi-cel has received FDA approval for second-line indication just over this weekend, so it is good news for our patients.