Paediatric leukaemia treatment regimens lead to improved outcomes in adolescents and young adults

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Published: 7 Dec 2014
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Dr Wendy Stock - University of Chicago, Chicago, USA

At a press conference at ASH 2014, Dr Stock presents the findings of her study which indicated that paediatric treatment regimens, which were generally higher in intensity, would be more effective on teenagers and young adults than adult regimens.

Read the news story for more.

These data really started fourteen years ago at this ASH meeting when we presented data showing that young adults, ages 16-20, who were treated on adult co-operative group studies in the United States fared much worse than the same age group who were treated on paediatric studies. That became a very important question to many in the world of ALL therapy and others around the world found exactly the same results that young adults who were treated on paediatric trials fared much better when compared to young adults, the same age, who were treated on adult oncology group studies. So over the years we developed a protocol that was taken exactly from a paediatric group study and we applied it to what we define as the young adult population, ages 16 up to age 40, on a United States co-operative group study. So we were asking the question whether adult haematologist oncologists could achieve similar results in a slightly larger age range using a paediatric protocol. We hoped to describe the toxicities and compare these with outcomes of young adults ages 16-29 years old who were treated on an identical arm of a paediatric protocol and to analyse these outcomes by presenting biological features which I’m presenting today. We also want to analyse patient and physician adherence since we believe that this is also a very important factor in outcome and outcomes based on psychosocial characteristics of the patients. Those data are not going to be presented at this meeting, they are still undergoing analysis.
So this is the regimen, as I mentioned it is taken identically from one arm of a paediatric cooperative group study and it is using a paediatric regimen which is particularly intense in the use of very standard, very established drugs including glucocorticoids, vincristine and pegylated form of asparaginase. Very intensive therapy to the central nervous system and prolonged maintenance therapy and this was identical to a paediatric trial but applied to young adults by paediatric haematologist oncologists.
We entered 318 patients over a period of about five years and of those 296 were eligible for analysis. The ethnic distribution is shown on the slide here. Importantly, Hispanic patients have a higher frequency of ALL and 16% of those enrolled on this study were of Hispanic or Latino origin. 61% of the patients were male and the median age of the study was 25 years with the distribution as shown here. The majority of patients were between the ages of 20 and 29 years. Most of the patients were in quite good shape when they started treatment. Importantly, one of the questions about toxicity with paediatric regimens applied to adults is whether or not if you’re a heavy person you can tolerate these regimens. Amazingly, possibly sadly in the United States, almost a third of our patients had an elevated body mass index and 7% were morbidly obese.
These are the results, I’m not going through the toxicity data today in the interests of time but I’m happy to talk about that later. The event free survival at two years, which is still early follow-up, is extremely much better than what we have seen in historical controls and it’s 66% event free survival at two years for all patients and overall survival is 79% on the study to date. This was with a median follow-up of about three years now.
So, in conclusion we noted that the paediatric regimen administered by adult haematologist oncologists was validated in a large North American inter-group trial. We had on schedule accrual, low treatment related mortality. I want to emphasise that our overall mortality was identical to that applied by the paediatricians with the same regimen. The event free survival of 66% and overall survival of 79% is a significant improvement compared to the 34% event free survival in the historical controls in our previous co-operative group study but longer follow-up is needed to validate these results. Our outcomes are very similar to other prospective international studies which applied paediatric regimens to young adult population of acute lymphoblastic leukaemia.
We also looked at some biological factors which are very interesting. I’m not going over those data in specific today but the presence of a specific genomic signature called the BCR-ABL1-like signature and overexpression of a particular gene called CRLF2 is common and associated with a significantly worse survival in these patients. In a multivariable analysis aberrant expression of this one gene, CRLF2, was associated with both worse event free and overall survival. Absence of minimal residual disease following induction therapy, which we’ll present data on similar to what Dr Wood presented, was associated with excellent disease free and overall survival. Based on these data we, in the US co-operative groups, are going to use this regimen as a foundation for future studies where we hope to add new targeted antibodies and newly applied kinase inhibitors to eradicate minimal residual disease which we have shown to be a very important factor and we hope that that will result in further improvements in survival for this group of patients.