EHA 2016

Novel therapies for older patients with AML and MDS

Prof Naval Daver - MD Anderson Cancer Center, Houston, United States

I’m presenting our phase II data with vosaroxin in combination with decitabine in elderly untreated AML and MDS patients. This is a study we’ve been doing now for about two years, we have 62 patients and we’ve seen very high response rates and good tolerability with the combination and we’re excited to present our results here.

Just as a bit of background could you maybe give us some description of the overlap between MDS and AML?

Sure, MDS and AML are basically very similar diseases and the difference is the aggressiveness of AML as compared to MDS. So the way we usually do it and the WHO has differentiated these diseases is people who have less than 20% blast, which are the abnormal cells in the bone marrow, are considered MDS or myelodysplastic syndrome, whereas those who have more than 20% blast in the bone marrow are considered as AML or acute myeloid leukaemia. So it really is a similar disease process but just when it becomes more aggressive we say it’s gone from MDS to AML.

The treatment that is in question here, can you tell us more about that?

So the treatment is a combination of two drugs, the decitabine is a standard agent that has been used for both MDS and AML now for more than ten years. It actually is approved in Europe for treatment of AML and it is on the NCCN guidelines in the United States for AML and is used very frequently in patients who are considered to be not fit for chemotherapy or high dose chemotherapy which is a large population in the age group above 60 or 65. So decitabine alone has a response rate of 20-25% and the responses usually are short-lived and the overall survival in two phase III studies in patients who were older and unfit for AML treated with decitabine was about 8 months. So our idea was to build on the single agent decitabine experience and see if adding another active agent, vosaroxin which had shown activity in elderly AML in the first salvage, could improve both the response rate, the durability of the response and ultimately overall survival. And we did see improvements in all these parameters in this group of patients in our phase II study.

Can you tell us the patient cohort, how they were selected?

These were all patients who were above 60 years of age and they had to be considered unfit for standard induction chemotherapy which is high dose chemotherapy. Unfit was usually decided by the treating physician and, as a lot of data has shown, the treating physician is the best person to make that judgement. So they were usually people above 65 or 70 or they had a poor performance status or they had a high white count at presentation or they had adverse cytogenetics. So these were usually the criteria that would help to determine the unfitness. There was no upper age limit, the patients could have any form of AML or high risk MDS. So these were the people who were eligible.

Can you give us some more detail on these results? Any percentages, numbers?

Of the 62 patients we have treated the remission rate or the response rate was 75% which is very favourable compared to the response rate of 20-30% that you get with single agent decitabine, so double or even maybe three times higher. We also saw very good tolerability, the early mortality or the number of people dying within 60 days was 10% or less, especially at the selected dose of 70/m2 of vosaroxin. This compares actually very equivalent to decitabine single agent and now we have some more mature data looking at survival and the median survival we’re getting with the chosen combination of vosaroxin 70/m2 and decitabine is about 17-18 months which is much better than the 8-11 or 12 months that we get with single agent decitabine in a similarly matched population, both at our institution and at other institutions in Europe and the US. So we’re very excited and I think the next step will be to compare the decitabine vosaroxin to other standard frontline AML treatments such as decitabine or high dose chemotherapy in a randomised fashion and see if these results continue to hold up.

You mentioned some of the next step, are there any ongoing trials that are in recruitment phase or that might be reporting details soon?

There are two studies, one is the German group where they have the combination of a similar drug, vosaroxin, with another agent called azacitidine which is the cousin of decitabine, very similar response rates and activity. That study is going to be for high risk patients and it is either opening or should be opening soon. The British group is planning to do a very similar study in the front line elderly AML patients randomising them to our combination of vosaroxin decitabine versus the standard therapy with 3 7 induction. So both of those studies are either just started or will be recruiting and hopefully by next year’s conference we may have some early data.