AZA in MDS, and managing the older MDS patient

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Published: 4 Jul 2012
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Prof Valeria Santini – University of Florence, Italy

Professor Valeria Santini comments to ecancer on the best time to start azacitidine (AZA) therapy in high-risk MDS patients presenting with iron overload, and on the issue of continuation of therapy.  She outlines her critical review presented at the EHA 2012 on the data correlating iron overload and overall survival in MDS patients (both low- and high-risk).

 

Professor Santini addresses how to manage MDS patients with co-morbidities.  She notes the moderate response observed with AZA in patients with co-morbidities and that co-morbidities should not be an obstacle to patients being treated.  She emphasises that age is definitely not a co-morbidity, and not a contraindication to treatment.  What is crucial is patient evaluation and selection.  In the future, biological and clinical characteristics, as well as biomarkers, will be used to personalise treatment and many studies are on-going assessing what these might be in MDS.

 

Spliceosome mutations are common in MDS and Professor Santini comments on whether these could become an investigational therapeutic target in the near future.  Studies are on-going with spliceosome mutations in all types of MDS, but we are still far from applying these mutations in everyday practice.

 

Advice is also given for clinicians managing elderly patients with MDS, with emphasis on evaluating individual patients and managing each person according to these findings.

 

This programme was made possible with an educational grant provided by CELGENE.

17th Congress of EHA, Amsterdam, 14-17 June 2012

AZA in MDS and managing the older MDS patient

Professor Valeria Santini – University of Florence, Italy



What can we learn from the latest data presented at EHA regarding the best timing to start AZA therapy in higher risk MDS patients?

There is evidence that patients who start on azacitidine therapy and have high risk MDS do have a worse overall survival when presenting with iron overload. This is a very interesting observation telling us that when you have a patient who is eligible for azacitidine treatment, having high risk MDS and blast, you should start your treatment as soon as possible. Long term treatment you have to start and continue treatment for many months, possibly years if the patients respond; you have to continue until disease progression but you do not have to wait too long to start such a treatment to ensure that your patient is responding at his best level.

What new data are presenting at EHA 17?

Well, discussing and critically reviewing all the data that have been published over the last few years on iron overload and survival of especially low risk MDS patients, it seems that if you have an iron overload your expectance of life and your expectance of life without progression is lower than without iron overload. So avoiding heavy transfusions is an important point, I think. We have to learn from these observations how to manage at our best the MDS patients, both low risk and high risk.

What is your view on AZA use in routine clinical practice, for patients with advanced age and/or significant comorbidities?

Well you see this is a very important point because almost all the patients who have MDS are elderly patients and 60-70% of these patients would present with comorbidities besides being elderly, therefore we have to consider these variables before treating but we shouldn’t avoid treating them because of the comorbidities. Last year we presented data from our centre and other centres of the Italian MDS Group in which we showed that patients with moderate comorbidity have an optimal response to azacitidine not only but they do prolong their survival. Only patients with very high comorbidity scores do not have a significant advantage in being treated with azacitidine.  So once again the patient should be evaluated very carefully before starting therapy but comorbidities shouldn’t be an obstacle to be treated. Not to speak of age, age is absolutely not an obstacle to be treated with Vidaza and when you have a patient with a renal insufficiency then at that stage you should realise how bad is the renal insufficiency and adjust the dose of Vidaza according to the renal function. Other comorbidities are more, let’s say, important for overall survival but the response and the kind of response to Vidaza is not influenced by such comorbidities. So the pharmacokinetics of Vidaza may be influenced by renal function but overall you can surely adjust your treatment to any patient.

Can the sliceosome become an investigational therapeutic target in the near future?

The splices on mutations are very common in MDS and some of them have real correlation, direct correlation, genotype/phenotype, which is quite interesting from a biological point of view. Refractory anaemia with ring sideroblast harbour the DSF3B1 mutation in a very high proportion of cases and these reflect upon their better survival. Other studies have been started and are on-going evaluating splices on mutations in all types of MDS and indeed it’s a very interesting field but we are still, I think, a little bit far from being able to apply it on a routine base for everyday life. I am sure that the more we know about the functional meaning of these splices on mutation the more we could apply it in a clinical setting.

What are the next steps for the future of clinical research?

We will be working on several levels. We will be doing a clinical assessment and together a lot of biological and molecular biology assessing and testing, so all the mutations that are tested will be evaluated and in the end I can foresee the situation in which we have five or six mutations which are the most frequent ones and we could check immediately at diagnosis our patients and then just set them in a prognostic risk level or a score that is helping us in choosing the best therapy.

In clinical practice today, what should healthcare professionals treating patients with MDS be focussing on?

A very important message is that we should really take care of every single patient, so evaluate the patient for first of all his or her needs and for his or her general health condition and I would put as a last issue the age which is not by itself a problem once again. And then take care of any possible prognostic parameter that at this present stage we can use and evaluate. It is very important to have a complete evaluation of all patients which we want to treat.