EHA 2015

Factors influencing response to blinatumomab in relapsed/refractory ALL

Prof Max Topp - Würzburg University Hospital, Würzburg, Germany

You’ve been looking at blinatumomab, a very interesting compound. There’s a lot happening here at the European Haematology Association but first of all can you explain why it’s interesting, the mechanisms, what attracted you to this in the context of acute lymphoblastic leukaemia?

Blinatumomab is an immunotherapy, it actually links the T-cells to attack in this case ALL by recognising CD19 on the cell surface of the ALL cells. We have explored this drug quite extensively in two settings, one is in patients who actually have relapsed after front line therapy and also in patients who actually have maintained to be minimum residual disease status after front line therapy.

It also attaches to the T-cells, doesn’t it, and that’s useful.

Correct, that’s very useful. The T-cells are brought closely to the proximity of the ALL cells and if that happens these T-cells become serial killers and they’re able to ... several of these ALL blasts within the patients.

I know you’ve got a series of interesting studies in relapsed and refractory and also in patients with minimum residual disease, but what actually is new now? What’s happening, what are the new data coming out here in Vienna?

Well we have several questions that we are addressing. The first question is is there a particular patient population that we feel it’s very useful to be used, where it may even be practice changing? So the elderly patient population that we studied, now there are two bigger trials that we’ve published, we have 35 patients with relapsed refractory ALL and those patients usually have a very dismal prognosis, you can’t get them off chemotherapy in that situation. So hence exploring blinatumomab in those patients might be very beneficial and we can demonstrate that patients who are 65 years old and older than that have the same outcome like patients who are 18, 19 and 20. So it is the first compound that is able to actually exert its effects in the elderly patient population equally to the younger patient. So that is one thing we’ve been looking at. The second question is patients who have a relapse and the relapse is quite often still CD19 positive. So the question is can we retreat the patient with blinatumomab and this is the case. We have a couple of patients that we’ve done that now and we see a very similar efficacy in those patients which have been re-exposed to blinatumomab in that situation.

And what about patients with minimum residual disease?

Well we’re not going to show any data here at EHA. We have shown that blinatumomab has a very strong effect in converting a patient who is MRD positive to become MRD negative in a big, pivotal European trial showing that we have efficacy rates of about roughly 80% in those patients.

So could you summarise for cancer doctors what is now coming out as the clinical potential of blinatumomab in this disease?

Two things. One is the MRD situation, so a patient who gets front line chemotherapy and remains to be MRD positive which is the most prognostic factor for a response or death in these patients, blinatumomab can convert those patients to be MRD negative as it’s a very strong compound with a response rate of 80%, we’ve confirmed that. So that’s number one and number two, it is for patients who are relapsing in two settings very important: a) in the younger patient you have a chance of getting into remission and then being transplanted so they have a second crack at being cured. And in the elderly patient population it is clearly a compound that can actually convert the patient to be without the usual side effects of chemotherapy to still extend their life.

And the patients who don’t initially respond to blinatumomab, is there still a role for the agent in the future?

Obviously yes. We are looking at prognostic factors – who is going respond, who is not going to respond on blinatumomab. We’ve learned some lessons in that context; in the MRD situation, obviously with a high response rate of 80%, it’s difficult to identify patients. In the relapsed refractory situation where roughly half the patients will be responding there seems to be a tendency that patients with low tumour burden do better than the patients with high tumour burden. So one concept that we are thinking of is to reduce the tumour burden up front by adding chemotherapy, mild chemotherapy, that would not impair the T-cell function and then come in with blinatumomab. Because patients with low tumour burden, so someone who has 25% blasts on average, will have a response rate which is 73% whereas a person with high tumour burden, more than 50% blasts in the bone marrow, only has a response rate of 30%. So if you could reduce up front with mild chemotherapy or dexamethasone the blast counts to lower than 50% we would even have a better chance of achieving.

So that’s for the future, then.

That’s for the future.

But now to wrap it up, what’s the take home message for therapy of acute lymphoblastic leukaemia using this bispecific antibody?

This is the first agent that is going to be useful to treat leukaemia that is not based on chemotherapy with a high response rate.