I want to thank you all for being here. I have the pleasure of representing our group, our investigators from multiple countries that embarked on this study of tisagenlecleucel in large cell lymphoma. This is a longer term follow-up of the preliminary early data that was presented last year at ASH. Just to state that, again, you saw some of the early part. Tisagenlecleucel is the first approved gene therapy, the first approved CAR therapy in the United States; May 1st 2018 it was approved for large cell lymphoma. It is a single arm, open label trial so there’s no randomisation, we know what patients are getting. We will update this analysis as this is 19 months median follow-up. The reason this is important is that early on, when you look at data early, you can always worry that the trial has selection bias. You pick the best patients, it doesn’t represent real life. As you move into 19 months follow-up, the median 19 months, you are now looking at the real natural history of the disease. These are patients with multiply relapsed refractory large cell lymphoma.
The primary endpoint was best overall response, which is CR and PR, sorry, complete remission and partial remission, with key secondary endpoints of duration of response, overall survival and safety. Just for the event, this will be presented tonight in poster session; I’ll be there for most of it or Stephen Schuster who is our first author in the publication. This is just to announce that at nine o’clock this morning this paper has just been published by The New England… it was announced for publication by The New England Journal of Medicine.
As far as the data, the overall response is 54% of which 40% were complete remissions, 14% were partials. Of the patients who had partial remission we do know that half of them went on to develop complete remission over time so the drug continues to work again over time – you can convert from partial to complete. The overall response data was seen; there’s multiple subgroups of large cell lymphoma, it’s a very complex disease, but with all the potential prognostic subgroups we could not see a predicted group that was likely to be favoured or also predicted to fail with CAR T. Also important is the median duration response was not reached for the patients who were responders. For patients who were in complete remission over half of them, the median, remain free and alive with a median overall survival not being reached. For all patients infused it was 11.1 months.
The figure on the right actually compares as an overlay of the data from the JULIET study compared to one prospective as well as one retrospective study of similar patient population. Again, early on you have patients that will fail but what we see is we’re approaching again a plateau where we’re definitely seeing a change in the natural history of the disease to the best of our ability to interpret the data.
As far as safety, we have similar profile but not to the same degree as tisagenlecleucel when treated with acute lymphoblastic leukaemia. It’s a lower degree of the cytokine release syndrome and neurotoxicity. This may be in effect related to the fact that when you infuse the cells they don’t immediately encounter in the same vascular space their target antigen. They have to traffic out of the vascular space into actually a lymph node or spleen or other organs. So this, it’s hypothesised, may at least contribute to lower degrees of the adverse events seen but we still do see 25% with advanced grade 3/4 GVHD. Again, I would also share that this grading system is a very liberal system that over-identifies toxicity compared to the Lee criteria which has now become more generally utilised.
Since the previous report no new deaths due to any cause other than when patients with disease progression, no treatment related mortality was seen throughout the entire study. There were three early deaths, all related to lymphoma that progressed through.
So, in conclusions to share with you, this is the data with a longer median follow-up of 19 months. Just to say again the high points – the overall response was 54% and for patients responding the median duration of response was not reached. In a similar population of patients we would have predicted a less than 10% complete remission and a 5 month median survival. Thus it was improved over historical options and I would say the adverse events were similar.
This is just a final slide to say that when you begin work, this is the beginning not the end. What we are doing is hoping you’ll hear about ways that we can build on primary first generation T-cell therapies. We have six current projects that are coming out of this database, some looking at dosing rationale. We are doing two presentations – on Monday we’ll be looking at regrading toxicity using the Lee scale or the Neuro-Tox scales that have become more commonly used. We’re also doing work on health economics as well as examining what happens when the cells are given in remission. So I want to thank you for the time and appreciate the effort and I also will vouch for Dr Alvern. This is the importance… this has become a health economic issue that we all need to be aware of and highlight. Thank you.