The ZUMA-12 is a single-arm phase II trial where we evaluate axi-cel as part of first-line therapy for patients with large B-cell lymphoma. Patients with high-risk large B-cell lymphoma, defined as either double-hit or triple-hit lymphoma, or large B-cell lymphoma patients with high IPI score of 3-5, have historically had increased risk of relapse and decreased PFS and OS with standard chemoimmunotherapy. So it is in this context we evaluated the value of axi-cel in a study involving 40 patients.
To be eligible these patients had to have high risk large B-cell lymphoma based on histology with double- or triple-hit or large B-cell lymphoma of IPI of 3-5 but also they had to have a positive interim PET scan with a Deauville score of 5 after two cycles of standard chemoimmunotherapy.
Once these patients were enrolled and underwent leukapheresis to generate the product they could receive optional non-chemotherapy bridging and then once the product has been generated receive the standard Cy/Flu conditioning followed by a single infusion of axi-cel. The primary endpoint for the study was complete response rate.
In the 40 patients enrolled and treated on this study we observed an overall response rate of 89% and a complete response rate of 78%, and after a median follow-up of 16 months 73% of the patients remain in ongoing response. In terms of safety we observed that this therapy is quite well tolerated in this first-line setting and no new safety signals have been observed with axi-cel compared to prior reports of this agent in the third-line setting of large B-cell lymphoma patients.
We also compared the product profile in patients with ZUMA-12 in the first-line setting versus the CAR T product profile treated in the third-line setting with axi-cel. We found a higher frequency of CCR7 positive CD45RA positive T-cells in the ZUMA-12 patient CAR T products compared to ZUMA-1 and this associated with the higher expansion in vivo post-infusion which has previously been correlated with better clinical outcome.
So, overall, this study demonstrates that axi-cel may benefit patients exposed to fewer lines of therapy and is potentially effective for patients with high-risk large B-cell lymphoma in the first-line setting.
What are the next steps?
At this time we are in discussions to potentially consider a randomised trial to evaluate axi-cel in the first-line setting, especially in patients with high-risk large B-cell lymphoma to compare it head-to-head with standard chemoimmunotherapy.