T cell therapy for ALL

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Published: 11 Dec 2017
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Dr Max Topp - University of Wurzburg, Wurzburg, Germany

Dr Topp speaks with ecancer at the 2017 ASH annual meeting about results from the ZUMA-3 trial looking at KTE-C19, an anti-CD19 chimeric antigen receptor T-cell therapy, in adult patients with relapsed/refractory acute lymphoblastic leukaemia. 

He goes on to say that KTE-C19 has shown promising efficacy in adult patients with relapsed/refractory acute lymphoblastic leukaemia.

The safety profile was generally manageable, though Dr Topp highlights the significant impact of PI3K pretreatment on patient outcomes, and additional approaches to improve the risk profile are being explored.

ecancer's filming has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.


At ASH a lot of data has been presented, updates of clinical trials treating patients with ALL. There is currently some very interesting progress; we have now seen that the Novartis product has now been approved by the FDA for the treatment of relapsed refractory ALL in patients under the age of 25 based on their phase II trial. ZUMA-3, which is a company sponsored trial from the company Kite, has been reporting on their dose finding phase I trial in patients with relapsed refractory ALL. So far about 39 patients have been treated, the question was which dose to be used and looking at 2x106/kg, 1x106 and 0.5x106 cells given to the patients after a relapse, refractory ALL patients. It’s clearly that there is a tendency that the safety profile seems to be improving with a lower rate of cytokine release syndrome of higher severity if you give the patients a lower dose of CAR T-cells in these patients without losing efficacy for patients who have been heavily pre-treated. What is also quite important is that also patients who have already seen CD19 directed therapy via blinatumomab also had a chance of being responders with this kind of therapy. So there’s a sequence that you can reimagine, even blinatumomab treatment failures can move on to receive CAR T-cell therapy in these patients.

This is a trial that has only been done in the US so the advantage of course that the T-cells are produced centrally at Kite Pharma in California and then are shipped to the sites so the downtime from leukapheresing the patient to actually treating the patient is less than three weeks which is actually quite favourable for this quite advanced technology and is very helpful. Nevertheless, still there are patients, if you say all comers, not every patient will actually be treated. You will lose patients due to progression; you will lose patients to production problems potentially in that situation, that is the caveat in that situation.

So where do you see this going? Obviously this is still, for this product, early days. It has to be seen in a phase II and phase III trials what it is, the potential in the real world. But overall it’s to be said that this is clearly something that will be established as a line of therapy, potentially the first or the second relapse treatment for patients with ALL. Knowing that patients who are responders with CAR-Ts is evidence that those patients are even long-lasting responders, potentially maybe even cured which is a difficult word to use in ALL, but time will tell after a couple of years. So I think that is a clear option for our patients with relapsed refractory ALL.