Blinatumomab has promising effect on hard-to-treat, rare acute lymphoblastic leukaemia subtype

Published: 6 Dec 2015

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Prof Giovanni Martinelli - University of Bologna, Bologna, Italy

Prof Martinelli talks to ecancertv at ASH 2015 about the effects of the tyrosine kinase inhibitor blinatumomab in patients with Philadelphia-positive (Ph ), B-cell precursor acute lymphoblastic leukaemia (ALL) who had relapsed or who were not responding to their current treatment regimen.

This is a very rare population of patients in a very rare disease, Prof Martinelli observes, which is important because there are few options once treatment with tyrosine kinase inhibitor therapy fails and the prognosis of patients is rather dismal.

Results from the Phase II, single-arm, multicentre ALCANTARA study, however, suggest there could be a benefit of using the bispecific T-cell engaging (BiTE®) antibody construct blinatumomab.

ecancer's filming at ASH 2015 has been kindly supported by Amgen through the ECMS Foundation. ecancer is editorially independent and there is no influence over content.

ASH 2015

Blinatumomab has promising effect on hard-to-treat, rare acute lymphoblastic leukaemia subtype

Prof Giovanni Martinelli - University of Bologna, Bologna, Italy

You have been looking at acute lymphoblastic leukaemia and this is patients with refractory or relapsing disease who may well have already received a couple of TKIs, a couple of different ones, and they are very poor prognosis. What were you trying to do with them? What was the big issue that you were looking at here?

This is a very rare population and a very rare disease, the Ph positive acute lymphoblastic leukaemia. But they are very important because in the last years there was an emerging treatment with the TKI which is a tyrosine kinase inhibitor of second or third generation giving very important results. However, a majority of these patients relapse frequently, particularly in the elderly population, and they have no chance to get additional treatment. The prognosis is still poor in the majority of these patients.

Now you’ve been using blinatumomab which is a BiTE, it’s a special kind of TKI and it’s a bispecific T-cell engaging antibody. What does that mean?

It’s a new compound, very, very emerging, very new in the concept. It’s a molecule that binds the effector of response, the T-cell killing response, against leukaemia. This makes drive the leukaemic effect, anti-leukaemic effect, of our T-cells against the blast CD90 positive. So it’s sort of restoring immuno competence in our body, that’s a very promising approach.

It sounds a very interesting idea. What did you do in the study?

We studied 45 patients with Ph positive refractory relapsed patients, most of them very aged, to the blinatumomab. It’s a continuous infusion of this compound for 24 hours for 28 days, so continuous infusion. The patients stay for a long time with this drug in a very small amount of drug infusion. They restored the activity against leukaemia so it’s a sort of re-emerging of our immunity against cancer in our body. They respond very well, we get 45% response in the majority of the patients, 35 of these were complete pathological response and 88 of this population, over all the patients, have a very deep molecular response which means that they respond very, very well.

What might this mean, then, in clinical terms? It’s a relatively rare group of patients but how might clinicians think about applying a drug like blinatumomab?

It is not clear until now because the advantage is enormous in the majority of the patients. But we don’t know how much enormous it will be or can be in this sort of patient. The majority of these patients have no transplant procedure opportunity so these drugs means that they have the possibility to be cured without transplantation and without chemo. That is absolutely a new entry in the majority of the population - over 55 years old the majority of the patients can probably be cured without chemo and without transplantation. We don’t know really what happens when you use these drugs up front because this was a relapsed refractory population, however, this could be very, very emerging new compound for this poor population for our heroic patients.

In this setting of refractory and relapsing ALL could you give me some kind of picture? Could you paint a picture of with the drug or without the drug? How big a difference – you said cure there?

Yes, it could be important because if we will be able to obtain a complete response in the majority of patients we can avoid transplant. We know that we get a tremendous power with the second generation, third generation TKI, the combination of this drugs to the second generation and third TKI will be very useful in the majority of the patients in the future.

So what should doctors be making of your results right now?

I think the majority of the patients have to take care this opportunity for the patients in relapsed and refractory Ph positive acute lymphoblastic leukaemia.

And the take home message about blinatumomab in ALL in this severe patient group?

Yes, the message is this is probably not a promise but is certain at this moment for the majority of the acute lymphoblastic leukaemia population.