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Thank you very much for listening. I'm Guillermo Garcia-Manero from the Department of Leukemia at MD Anderson Cancer Center where I serve as the Chief of the Section of Myelodysplastic Syndromes (MDS). In the next few minutes, I'm going to discuss with you some of the more important presentations in my opinion in MDS at the ASH Meeting this year in San Diego in 2016.
The first presentation I want to highlight was presented by Dr. Montalban-Bravo from MD Anderson where he showed data in terms of the impact of mutations, and more importantly the number of mutations, in the prognosis and response to hypomethylating agents in patients with MDS. A number of further publications and presentations have shown or are showing similar results, but this is a concept that I think is important in which not only particular mutations but the number of mutations seem to be very important when predicting outcomes with patients with MDS.
The next presentation refers to what I think actually transformative concept. It was pioneered by two groups in Boston and most recently by investigators at Washington University where they showed that patients with therapy related myeloid neoplasm had evidence of clonal hematopoiesis, meaning mutations in their blood before they undergo chemo- and radiation therapy.
At this ASH Meeting, two oral presentations, one from Dr. Takahashi from MD Anderson and one from Dr. Padron from the Moffitt Cancer Center, expanded on this initial observation from the Washington University group, and they clearly demonstrate that a large majority of patients with therapy related MDS or AML have antecedent evidence of clonal hematopoiesis before they get any chemo or radiation therapy for their solid tumor cancers or lymphoma. I think this data is very important because first of all, it shows evidence that perhaps the paradigm of chemo and radiation therapy causing DNA damage may not be as clear as it may be more related to changes in cellular dynamics and secondly, may give us information or potential to develop some type of screening type of approach in patients at high risk for developing therapy related leukemia that as all of you know has a very poor prognosis.
In terms of new therapies, we showed actually quite a bit at the meeting this year. In the next presentation, this data that I presented with a new compound known as OPN-305. This is a monoclonal antibody against Toll-like receptor 2 and the data presented at the meeting showed that this agent that inhibits innate immunity signaling had quite significant activity particularly in red cell transfusion independency in patients with lower risk MDS but that had fail a hypomethylating agent.
Another presentation of interest also presented by our group is the initial pharmacokinetic and pharmacodynamic data with ASTX727 in patients with MDS. This new compound is an oral derivative of decitabine combined with a cytidine deaminase inhibitor. This combination actually allows for excellent PK and PD profile with oral decitabine an evidence that this oral compound actually may be as active as parenteral decitabine. I think this is very important concept because it may allow for development of total oral treatment programs for our patients with myelodysplastic syndrome.
In terms of also other hypomethylating agents in the next presentation, again Dr. Montalban-Bravo presented the initial results from a phase 2 study of guadecitabine or SGI 110 in MDS. As you know, guadecitabine is a second generation hypomethylating agent also a derivative of decitabine. Dr. Montalban-Bravo showed evidence of clinical activity and safety in patients with MDS using this compound as first line therapy. Again, this drug is also being tested a number of clinical phase 3 trials both in MDS and AML so it's an important data.
To conclude my presentation, I would like to highlight briefly two more studies. One, actually also refers to the use of immune therapy along the lines of Toll-like receptor 2 presentation earlier but this time with inhibitors of PD-1 and CTLA-4. The first one was a presentation by multi-centered trial of the use of pembrolizumab in patients with MDS after HMA failure. This was a pilot trial, called KEYNOTE-013. We treated 27 patients and the response rate was low with the pembrolizumab but particularly in patients with intermediate-1 disease we're seeing an impact in survival that was not expected with three of these patients actually being long term survivors of this disease with HMA failure. That I think is a very positive signal.
We followed this trial with a study performed at MD Anderson of the combination of nivolumab or ipilimumab with or without azacitidine in patients with myelodysplastic syndrome either up front or after HMA failure. The data has a short follow-up, but we're starting to see significant responses with single agent ipilimumab. This is also important and trends in survival that actually better than expected particularly in the subset of patients with HMA failure.
To conclude on the last presentation, I like to highlight a talk that was given during the AML session but with a compound that will have an application in MDS that is oral azacitidine or CC-486 where we showed actually that this drug that is given for 14 or 21 days actually could rescue patients that had fail a traditional hypomethylating agent such as azacitidine and decitabine. Somebody I think that they work in MDS starting to translate into new assays for our patients in terms of prognosis more importantly new therapies and I'm grateful for this opportunity and thank you for listening to the presentation.