EBMT 2020 | Real-world efficacy & safety data: CAR-T in DLBCL

We have three pivotal studies to date. We have ZUMA-1, JULIET, and TRANSCEND NHL 001. Each one of these studies had variable management of toxicities, as well as varying inclusion/exclusion criteria, where the overall evolution was to have less restrictive eligibility criteria and more liberal use of medication such as tocilizumab and steroids. What we’re seeing is that across these studies, we see relatively comparable durable responses. Overall responses between ZUMA-1, JULIET, and TRANSCEND may differ, but I think the most important metric, being progression-free survival in these patients, is hovering around 35, 40%. And we look forward to see updated data moving forward and eventual approval with lisocabtagene maraleucel or the TRANSCEND NHL product.

And so, one big question that came up when we initially had the approvals of these agents was whether or not the overall responses we were seeing in our very selected patient population were going to be seen also in the pivotal studies. And so, one thing that we were able to do in the U.S. and elsewhere is use the CIBMTR, which is basically our central registry for bone marrow transplant, immune effector cell therapy, and we’re able to look at the first patients who were actually infused. These data were presented initially at ASH in 2019. And so based on the axicabtagene ciloleucel CIBMTR registry of 533 patients, what we were seeing is that very comparable overall response rates of around 74% compared to about 80% seen in ZUMA-1, with similar findings of an overall response rate around 58% for tisagenlecleucel, with a CR rate of around 40%.

We’re still waiting for the long-term followup in these cohorts. However, what we’re expecting is that we’re expecting about three-month PFS of around 60 to 70% seen in tisagenlecleucel and similarly for axicabtagene ciloleucel. So, overall, I think these are really encouraging data showing that even in the real world use, where patients who would not have met eligibility criteria for say ZUMA-1 or JULIET, we’re seeing durable responses that are actually holding in these patients.

There is one other abstract that was presented at ASH 2019 by Riedell et al., where they actually did a comparison of axicabtagene ciloleucel and tisagenlecleucel at multiple centers who are prescribing both at the same time. And what we were seeing is overall response rates between 51 and 64% for tisagenlecleucel and axicabtagene ciloleucel, as well as some encouraging toxicity data where we basically saw no severe CRS or ICANS with tisagenlecleucel. So overall, again, very optimistic that the responses are holding and, if anything, the toxicities are actually decreasing.