ASH 2015

Rituximab plus chemotherapy improves outcomes in acute lymphoblastic leukaemia

Dr Sébastien Maury - Hôpital Henri Mondor, Créteil, France

You’ve been looking at acute lymphoblastic leukaemia and particularly a new treatment. What did you decide to do and what were the big issues here?

We decided to test if the addition of rituximab, which is an older drug, may improve the outcome of patients with acute lymphoblastic leukaemia of the B-cell lineage, Ph negative disease. To answer this question we randomised the addition of rituximab to the standard chemotherapy in a 1:1 ratio and we demonstrated that patients who received rituximab had an improved outcome. The primary endpoint was event free survival and this was significantly improved by the addition of rituximab.

Now, these particular patients who are CD20 positive and Philadelphia chromosome negative, what would they have been treated with if you didn’t add rituximab?

They would have received standard chemotherapy, which the standard now is to use a dose intensified regimen inspired by the paediatric regime that are translated for adult patients. Some of those patients based on their criteria of risk are offered allogenic stem cell transplantation in first remission.

You had freedom from disease, you also had an improvement in overall survival. What are the numbers that came out of this?

Overall survival is around 60% which is a good result. Actually, the benefit in terms of overall survival was only observed significantly at the statistical point of view for patients who were not transplanted in first remission with an allogeneic donor. When we analysed the whole population, including the transplanted and non-transplanted, this benefit appeared only as a statistical tendency.

What was the benefit in terms of event free survival then?

The gain was from 52% to 65% at two years.

So what are the clinical implications of your findings, would you say?

I think that rituximab in addition to chemotherapy becomes a new standard of care for these patients who express CD20 at diagnosis.

Would you recommend the use of rituximab now or should there be further approval?

No, I think they can use it now based on our experience and past experiences from other groups in controls to do with historical controls but not randomisation. Here we bring the randomised study that I believe brings sufficient information to add this antibody to up-front therapy of these patients. Although some specific points need to first be studied, such as the definition of the optimal dose schedule, the relationships with allogenic stem cell transplantation in first remission and other points that will be further studied.

So the take-home message for doctors is what?

Add rituximab to CD20 positive B-cell ALL in adults.