Anaemia update from EHA 2013

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Published: 28 Jun 2013
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Prof Valeria Santini – University of Florence, Italy

Around 80% of patients with myelodysplastic syndromes (MDS) will develop anaemia. In low risk MDS, this is a key symptomatic feature. It has a significant impact on patient quality of life and cardiovascular function.

In addition to red blood cell transfusions, recombinant human erythropoietins (ESAs) are a mainstay of therapy. However, there are still clinical challenges regarding when to initiate therapy, deciding on the optimal dose of ESA and determining which is the most efficient type of ESA, and the duration and outcome of these treatments. ESAs and biosimilars are not approved for the treatment of MDS, even though they are very active. Anaemia in elderly patients with MDS can lead to cognitive impairment in addition to fatigue.

Eltrombopag increases platelet counts in immune (idiopathic) thrombocytopenia (ITP). However, it has also shown effectiveness in improving haematopoiesis in aplastic anaemia. It has also been investigated in both high and low risk MDS patients. There is still an unmet need to improve erythropoiesis in patients with solid tumours and haematological neoplasms.

This programme has been supported by an unrestricted educational grant from Janssen Pharmaceutica (A Johnson & Johnson Company).

18th Congress of EHA

Anaemia update from EHA 2013

Prof Valeria Santini – University of Florence, Italy


What are the consequences of anaemia in low risk MDS?

We all know that MDS, myelodysplastic syndrome, are very complicated diseases but anaemia is a common feature for more than 80% of these patients. In low risk MDS in the majority of cases it’s the only problem and it’s very symptomatic and really worsens the quality of life of these patients. These patients may have a very long survival, therefore we need to do something and improve their haemoglobin levels. Now, of course, transfusions are still there and we may transfuse patients in case of need but nevertheless you should really take into account that these patients are facing 10-13 years, maybe, of transfusion which is very hard and really it worsens your quality of life.

There are several tools we may use to improve their anaemia and there are several drugs and agents, of course. The main consequence is not only regarding quality of life, it’s regarding heart functioning and you know that there is a heart remodelling, even for as high or as low as 10.5g/dl of haemoglobin, so quite early. Heart remodelling may decrease heart function and this is a serious consequence of chronic anaemia.

MDS patients are chronic and we should face this problem seriously. So of course we can treat them with ESAs and we have a battery of these agents now. We have the erythropoietin alfa and beta; we have darbepoetin and we have now coming in the biosimilars. Now none of these drugs and these agents are approved for treatment of MDS which is quite a shame because they are very active. The epo alfa and beta and darbepoetin can increase haemoglobin and normalise haemoglobin levels in as much as 70% of the patients if they are selected properly and chosen before therapy whereas there are not many data, I would say there are very scarce data, regarding biosimilars. Biosimilars have been used for chronic anaemia in renal failure, renal insufficiency, and they have been used in chemotherapy related anaemia, not as much in MDS. And I would add that a study, a randomised study or a non-inferiority study at least, should be needed. Nevertheless there are two studies in this moment going on to approve ESAs for treatment of MDS. This is really an urgent need because we can improve the quality of life, decrease the side effects of anaemia for these patients and these patients are elderly, chronic, so they may be a burden for the health system anyway so we don’t have to think only to the cost of the ESAs but also to the advantage of treating them properly.

Regarding the biosimilars, there have been reports of pure red cell aplasia following treatment with biosimilars because of the induction of antibodies. They seem to be immunogenic more than the originators. I cannot say much more about MDS and biosimilars, I wish I could but we have to wait for the studies and you know that health authorities are pushing for the use of less expensive agents for chronic patients so we would really like to know the cost effectiveness of these agents.

What type of problems are you experiencing when treating elderly patients?

You see, anaemia has been proven to be impacting on cognitive faculties of these patients. So on top of being weak, of having fatigue, they also have a cognitive impairment because of anaemia and it can be misjudged as an Alzheimer or other cognitive impairment but it may be due directly to anaemia. There have been several geriatric broad studies pointing the fact that, let’s say, the faculty of the elderly people affected by anaemia are really impaired in a broad way. So everyday functioning, not only the cognitive but also the practical functioning is impaired by anaemia. So I think it has broad consequences in all aspects, not only organ damage which is, of course, widespread but also on the everyday life.

What are your thoughts in regards to the newly released data on Eltrombopag?

Eltrombopag is a new agent. It’s a very interesting drug, it is an oral drug so easy to administer but because of that we have to not underestimate the potentiality of this drug, of this agent. It has been shown to increase platelets in a substantial way in ITP, immune thrombocytopenic purpura, but it has shown and it has been published very recently that it has an extremely high effectiveness in improving haematopoiesis in aplastic anaemia. This is extremely interesting because patients with aplastic anaemia who are refractory to immunosuppressive treatment may take advantage from this treatment in a substantial way.

So this improvement in haematopoiesis is not only regarding thrombopoiesis but also erythropoiesis and myelopoiesis heterogeneously, depending on the patient. But it’s extremely challenging, extremely intriguing results.

We have interesting results in myelodysplastic syndromes as well, both in the high risk and in the low risk. There is one Italian study led by Esther Oliva, and in which I’m involved, in fact, treating MDS low risk patients with Eltrombopag. MDS patients are not very often only thrombocytopenic, they are also anaemic and this drug seems to increase in a high proportion of cases the production of platelets. In high risk MDS patients who have failed previous therapy this drug is also effective in improving even if not the platelet numbers normalising them but it’s lowering transfusion, platelet transfusion, which is a haemorrhagic event which is an important goal as well. For aplastic anaemia the results are so interesting that there is a great interest on the effect of Eltrombopag on stem cells, haematopoietic stem cells, and quite a number of studies, biological studies, are going on in this moment to clarify this point.

So I think we will have news and there are two very interesting reports here at EHA on Eltrombopag and I think we will have more in the future.

What are the benefits and precautions that should be applied to having an oral drug like Eltrombopag?

Sure, if you offer a patient who has already a lot of drugs to take every day an oral drug, they will be much happier than having an injection. That doesn’t mean that once again we have to underestimate the drug and also the side effect. So there is always a danger that when you give an oral drug you just get the drug and say goodbye and this is not the case. Almost never is the case, but especially for new agents in which you have really to check and control the patients.

How does this impact on clinical practice and what are the next steps?

What we need is really a way to improve erythropoiesis both in patients with solid tumours and with haematological neoplasm. In the past few years there have been some warnings and some worries regarding the use of ESAs in patients receiving chemotherapy for solid tumours. In some instances there has been reported and demonstrated a shortening of survival instead of a prolongation of survival which is quite a problem. On the other hand the patients are every day experiencing a lot of symptoms and fatigue just related to the fact that they receive chemotherapy. There are few agents now which are in trials and which are in clinical trials and different from ESA and I think it’s very premature to say that we have a new way to stimulate erythropoiesis but I’m sure that in the near future we will have more data to discuss and more hope to give to these patients.