The second abstract is reporting on the interim analysis of the cohort 4 of the ZUMA-1 trial. The ZUMA-1 trial is a CAR T-cell therapy trial targeting CD19 in aggressive lymphomas. The question that is being asked here – can we improve by early intervention of steroids the safety for delivering this interesting therapy to lymphoma patients?
In the ZUMA-1 trial, the registration trial, the cohort 1 and 2, there were about roughly a third of the patients had grade 3, grade 4 cytokine release syndrome and also double digit neurotoxicities context. So the object of the cohort 4 study is to reduce this rate by intervention of early application of steroids if a patient develops cytokine release syndrome grade 1 or neurotoxicity at a low level. So we are reporting here on 20 patients and these 20 patients are matched quite nicely to the demographics of the cohort 1 and 2 of the ZUMA-1 registration trial in terms of age, disease burden and prior lines of therapy. But there are subtle differences in the tumour volume because in this cohort we also were allowed to give bridging therapy – steroids, rituximab or bendamustine – so the patients which entered then the clinical trial, are getting the CARTs, had overall a lower tumour burden when compared to the cohort 1/2 patients in the registration trial.
So the most important piece of information is that by using steroids very early onwards on grade 1 cytokine release syndrome there was only just a single patient who developed a grade 3 cytokine release syndrome out of 20 and none of them had serious neurotoxicity. So this is really quite significant when compared to the registration trial, the ZUMA-1 trial where there were about 25-30% getting grade 3, grade 4 cytokine release syndromes and also double digit figures of neurotoxicities.
So obviously this is just an interim analysis of the first 20 patients and there are still 40 which were recruited and we will be reporting on that during the ASH conference, the full dataset of those patients. Then it will be to be seen if these encouraging results hold up for this CAR T-cell therapy in patients with aggressive lymphomas.
The impact is quite obvious – by reducing the rate of patients going onto the ICU it means the safety profile of the drug, of the CAR T-cell therapy, is markedly increased. It would also be more cost effective to the system. CAR T-cell therapy is an expensive therapy and so if we can shave off by not putting patients onto ICU that is quite meaningful for patients too in that situation.