ASH 2015

Long-term outcomes after blinatumomab treatment

Dr Nicola Gökbuget - University of Frankfurt, Frankfurt, Germany

As you say, you’re working in adult ALL; you’re looking at something called MRD positive B-cell precursor ALL and in particular you’ve been using blinatumomab. Now can you tell me about that agent and why you were looking at this category of ALL?

OK. ALL patients are usually treated with intensive chemotherapy and in most of the patients achieve a so-called complete remission. That means that no blast cells are detectable in the bone marrow by microscopy. But there are new methods to detect the disease below this cut level, up to a level of 0.01% and this is called MRD. This sounds as if it is not a problem but it is a problem because patients remaining MRD positive have a high risk to relapse. They are refractory to the chemotherapy and have a higher relapse rate.

So what did you do with blinatumomab? Could you describe your study to me?

We couldn’t… if you just continue with chemotherapy the patient will relapse so what we did is using blinatumomab and blinatumomab has a different mechanism of action. It is a B specific antibody and it attracts T-cells of the body with one portion and brings them to the CD19 positive B-cell, so the leukaemia cell. And if the T-cells get very close to the target cells they start to proliferate, they get activated and they kill the target cells. They can detach and look for another target cell, therefore sometimes called serial killing.

So the bi-specific nature of this antibody made it more effective in fact?

Truly it is a therapy which activates the immune system of the body so you need T-cells in the body. The body just brings the T-cells to the target cell. This is actually the treatment, the T-cells make the treatment.

What happened, in fact, in your study? What did you find?

We found that approximately 80% of the patients with this MRD positive resistant disease developed a complete MRD response, so no longer MRD was detectable after only four weeks of treatment with the blinatumomab.

So it really cleared the disease out?

Yes, yes. At least down to a certain detection level.

What impact did that have clinically?

The impact is that first of all we can avoid a full haematologic relapse and the patients are in a good shape, then many of them proceeded to a stem cell transplantation as their final therapy. Some patients did not receive a transplant and they continued with blinatumomab maximum three cycles and so we have these both groups.

What in terms of the numbers in terms of a relapse free survival and the duration of remission, what did you get?

The overall survival, I think was the most important outcome, is above 50%. The median overall survival is 36 months and this is a big improvement. If you treat the same population full relapse the median survival is 6 months. This is really big progress and also the median remission duration and relapse free survival was 18 months and more.

Now there are two factors here: you are monitoring MRD and you are using blinatumomab. What is the clinical advice coming out of this study?

The advice is that you should identify the patients with MRD positive ALL and treat them before they develop a relapse and blinatumomab is a very efficient drug to do so.

Is that going to become a standard, do you think?

Certainly. MRD positivity is the most relevant prognostic factor in ALL and more and more people understand that you need to act on this. And blinatumomab is a drug where we have most experience now due to the study. Maybe in the future further drugs come up but now for B precursor ALL this is where we have most data.

So, to sum up, what are the practical messages that doctors should take out of this?

Every doctor should measure MRD in the ALL patient and if after a certain time period of chemotherapy the MRD stays positive they should look for adequate treatment and in B precursor ALL blinatumomab is a good way to treat.