Thank you Tom. Good morning everybody and it’s my pleasure in the name of my co-workers to present to you the first interim analysis presented of the global trial assessing the efficacy and safety of CTL019 in adult patients with relapsed refractory diffuse large B cell lymphoma. I have to disclose that this study was sponsored by Novartis and I have received personal compensation both by Novartis but also other companies including Celgene and Kite.
Having said that, the purpose of this research, as already mentioned, diffuse large B-cell lymphoma when failing primary therapy has a very dismal outcome. The five year survival of DLBCL is only 55%, really meaning that a substantial number of patients fail these very common haematological malignancies. CTL019 is a genetically engineered T-cell which expresses a chimeric antigen receptor, a receptor that recognises the CD19 antigen which is expressed on virtually all B-cell malignancies. During the treatment the T-cells from the patients are drawn from blood, cryopreserved, transduced and reprogrammed to engage and eliminate the patient’s cancer cells. Initial results from a single centre phase II study performed at the University of Pennsylvania had shown durable remission with a single infusion of CTL019 in patients with relapsed refractory DLBCL.
I mentioned already, it’s a global study, single arm, open label. There were 27 sites in 10 countries including six European countries which are depicted on this slide. It was performed in adult patients with relapsed refractory DLBCL using a centralised manufacturing and cryopreserved apheresis product. They had relapsed or progressed after two lines of prior therapy and were not candidates for stem cell transplant. Actually about half of the patients recruited in the study had received prior autologous stem cell transplant.
The aim was to improve the overall response rate of these patients. The results presented of this interim analysis include 51 patients who have been evaluated with at least three months of follow-up after the infusion of CTL019 or earlier discontinuation. The best overall response rate as shown on this slide was 59% with 43% of the patients achieving a complete response. What we consider the overall response rate at three months is 45% with 37% of the patients in complete response. If we look at the outcome of these patients the relapse free survival at six months was estimated to be 79%. At the present time all patients with responses at three months are ongoing responses at the time of data cut-off so despite the short follow-up of this study these are very encouraging results.
If we look at the safety of this treatment in these patients and look specifically at the adverse events that are on target, that are known to be associated with the use of these therapies, a cytokine release syndrome of all grades was observed in 57% but of grade 3 or 4 was only observed in respectively 17% and 9% of the patients. About one quarter of the patients had infections or cytopenias that were not resolved within one month. Neurological events were observed in one out of five patients with only 13% of the patients experiencing grade 3 or 4 neurological events which were all reversible. There were a few patients with febrile neutropenia, one patient with tumour lysis syndrome. So CRS grading was using a University of Pennsylvania scale and was managed in every centre using a protocol specific algorithm. Very important – there were no cases of cerebral oedema and no deaths attributable to CTL019.
In conclusion, this study, the JULIET, is the first global study of CAR T-cell therapy in DLBCL with a centralised manufacturing process. It met its primary objective of the pre-planned interim analysis with a best overall response rate of 59% with 43% of the patients achieving CR and 16% a PR. The adverse events which were expected were reversible, were effectively managed and the study personnel were trained in this multicentre study performed in four continents. There were no deaths related to the study, no cerebral oedema and it confirms the high response rate observed in previous studies and the durability of response in the previous single centre trial.
