CAR-T cell dosing approaches in treating acute lymphoblastic leukaemia

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Published: 17 Dec 2018
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Prof Bijal Shah - H. Lee Moffitt Cancer Centre & Research Institute, Tampa, USA

Prof Bijal Shah speaks to ecancer at ASH 2018 about the updated results of the ZUMA-3 phase I trial, which explores different CAR-T cell dosing approaches in adults with acute lymphoblastic leukaemia.

He explains that with the modified dosing approach used they found improvements in tolerability.

Prof Shah reports that the study found the lowest rate of neurotoxicity of the adult ALL trials.

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We’ll be updating our phase I results on the ZUMA-3 trial. This is a trial exploring different CAR T-cell dosing approaches in adults with acute lymphoblastic leukaemia. We’ve previously shared our data using cell doses of 2x106, 1x106 and 0.5x106. What we will be sharing today at the meeting is our outcomes with a modified safety approach in patients dosed at the 1x106 cell dose; just to clarify, this is 1x106 per kilo, these aren’t fixed doses.

With the modified dosing approach we did find a marked improvement in tolerability, specifically one out of the eight patients that were dosed developed grade 3 neurotoxicity, one out of the eight that were dosed developed grade 3 CRS, there were no grade 4 CRS or neurotoxicity events, no grade 5 CRS or neurotoxicity events. The other seven patients all did remarkably well. This is very exciting from our perspective; to our knowledge this is the lowest rate of neurotoxicity seen on any of the adult ALL trials and certainly a much lower rate of cytokine release syndrome than we were anticipating.

We will also be updating our duration of response data, this will be the first time that we will be showing this data. What we are seeing at the 1x106 cell dose is a median duration of remission of 12.9 months which is also very, very exciting to be able to share.

We did see that those patients at the 0.5x106 cell dose also showing very durable remissions. We are going to expand at the 1x106 dose, however, because we saw a higher remission rate at that dose relative to the 0.5x106.  In particular, our remission rate at the 1x106 dose is somewhere around 93% whereas at the 0.5x106, I can’t recall specifically, I want to say it was something like 60%, 50-60%.

What’s next?

We have launched the phase II, it is already open in Europe and the United States. It is actively accruing, I think around 15 subjects a day have been screened and have either already been infused or are pending infusion.