by Dr Mike Dennis,  
Consultant Haematologist, The Christie, Manchester

The 57th meeting was held in Orlando, Florida (USA) in December 2015 and was attended by more than 20,000 professionals interested in blood disorders.  Here is a summary of Dr Mike Dennis report. Read the full report here.

Biology of MDS

An increasing number of specific gene mutations are being identified in patients with MDS.

An international collaboration of more than 3000 patients’ samples with MDS was presented by Rafael Bejar, Assistant Professor, University of California, San Diego (USA). This provided a wealth of further knowledge on the types of mutations that occur, their potential prognostic impact and potential therapeutic targets.

Lee presented work on spliceosomal mutations, demonstrating their importance in the generation of MDS and how they can be modulated by therapy, therefore creating a new therapeutic strategy for future clinical trials.

In the interim, there are relatively simple pathology tests (such as P53 staining) that can be very informative in clinical decision-making for clinicians.

Developments in MDS therapy

For me, the main themes explored from a therapeutic perspective were
1. Treatment options for low risk patients no longer responding to Erythropoiesis-Stimulating Agent (ESA). 

Luspatercept (previously known as ACE-536)  is a protein that causes a rise in haemoglobin in healthy volunteers.  Professor Aristoteles Giagounidis MD, Head of the Department of Oncology, Haematology and Palliative Care, Marien Hospital, Düsseldorf (Germany) presented results of a study in Germany where 58 patients with low risk MDS have been treated, if they’ve failed or are unlikely to respond to ESA. The majority went on to an extension study where the response rate was nearly 70%, with most responses being long lasting and the treatment well tolerated.  An international trial ‘MEDALIST’ is now being planned.

Other similar agents, such as Sotatercept (ACE-011), are also in clinical development.

2. Telomerase 

Most cancers have high levels of telomerase, including the more aggressive forms of MDS. Imetelstat is a strong inhibitor of telomerase which, in clinical trials for myelofibrosis, was found to have a high response rate in patients with specific mutations also common in MDS (SF3B1).

Aref Al-Kali MD (Assistant Professor of Medicine, Mayo Clinic, USA or Tel-Aviv Sourasky Medical Center, Israel) presented the initial findings of a trial in MDS patients with low risk disease, suggesting a good response rate with a reduction in transfusion requirements and good tolerability – again, there are trials planned with the agent in the UK in the near future.

3. Treatment options to improve the response rate with azacitidine 

There were a large number of studies looking at combination therapy with the current standard azacitidine to improve response rates and therefore survival whilst remaining well tolerated and preserving life quality for patients.

Eltrombopag (EPAG) is an oral medication which can stimulate platelet production. Professor Moshe Mittelman MD, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel presented the findings of the ASPIRE study where EPAG was used in patients with advanced forms of MDS and low platelet counts, indicating it appears safe and well tolerated with some activity. Again, it was noted that it can stimulate neutrophil and red cell production. EPAG is currently undergoing trials in the UK in combination with azacitidine (ELASTIC trial).

4. Transplantation 

Randomised trials in stem cell transplantation are a rare event partly due to the complexity and the clinician experience with their approach to various clinical transplant situations. The MAvRIC trial was presented by Scott - 272 patients with MDS/AML who were transplanted across 32 transplant centres in the US.

The findings largely supported the already widely held belief that full intensity stem cell transplants are more toxic but have a lower relapse rate when compared to the more frequent approach of reduced intensity conditioning.

Summary

From a clinician’s perspective, patients with MDS are all too often a significant challenge with relatively few truly effective therapies available.

Our increasing understanding of the biology of the disease is creating more informed treatment decision-making and further therapeutic opportunities which can be explored. Progress in getting new treatments available for patients with MDS has, at times, been frustratingly slow and we are now looking at a future where further licensed therapies in MDS will not be far away.