Were there any presentations at ASH 2012 on the clinical aspects of MDS that you think patients might find particularly interesting?
There is some evolution in the classification systems used for MDS. For years, we have used the International Prognostic Scoring System (IPSS) as the standard system for prognostication. IPSS risk classifications help predict survival and determine what kinds of treatments will be used. The IPSS was recently revised – and there is a new system called the IPSS-R, signifying this revision. There were a number of abstracts presented that validated the IPSS-R, applying it to MDS patients in international medical centers to see if it could accurately predict survival in those patient groups. In fact, it worked in a variety of patient groups around the world!
One abstract that interested me was from a French group that took the IPSS-R and applied it specifically to patients who were on azacitidine (Vidaza®). This is important because both the IPSS and IPSS-R were developed around patients who did not receive any therapy for their MDS. So the goal was to find out if either of these systems could be used in patients who are receiving active treatment for their MDS. This French group showed that IPSS-R can be used to predict survival in patients who are treated with azacitidine, thus it is valid for a patient who is about to start azacitidine to use IPSS-R to predict how long that person will live.
However, keep in mind that IPSS-R is a new system, and doctors have to get used to using it just as much as patients need to get used to using it. In time, it may come to replace the IPSS, but that would be a least a couple of years away, and quite possibly longer, before it is widely used.
What presentations on specific therapies did you find interesting?
One interesting report was an update about the drug romiplostin (Nplate®) which has been FDA-approved for patients with idiopathic thrombocytopenic purpura (ITP). Patients with ITP have a low platelet count, not because of a bone marrow problem, but due to an autoimmune problem in which the immune system is attacking the platelets.
This drug had been earlier studied in patients with MDS who also have a low platelet count and in the largest study, it was found that romiplostin did improve platelet counts in about 40 to 50% of MDS patients with low platelet counts. This is good news, since we now have a drug that works for platelets in the way that growth factors like erythropoietin (Procrit®) or darbepoetin (Aranesp®) work for low red blood cell counts. Romiplostin can be considered a platelet growth factor, also called a thrombopoietic growth factor (TPO).
The problem was that while the randomized Phase 2 study was in progress, the data safety and monitoring board noticed that the patients receiving romiplostin seemed to have an increased blast percentage, and some of these patients progressed to leukemia. So the study was closed earlier than would have normally happened, and the last patients admitted to the study could not be fully evaluated as to whether they responded to romiplostin.
What I found significant was that the follow-up presented this year of patients from the original study who did or did not receive romiplostim reported that the percentage of patients progressing to leukemia was no different in the romiplostin group and the group treated with a placebo. In other words, with additional follow-up, there actually did not appear to be a higher risk of leukemia among MDS patients treated with romiplostim, compared to MDS patients not treated with the drug.
In a companion study from our group, we developed and validated a model to predict response in patients treated with romiplostin, based on prior platelet transfusion needs and blood levels of the hormone TPO. So just as there is a model to predict patient response for red blood cell growth factors such as erythropoietin, we now have a model to predict patient response with rominplostin.
One of the more common drugs used to treat MDS is azacitidine, or Vidaza®. This is given as a shot under the skin or into the vein through an IV line. More recently, a pill form of azacitidine has been developed and studied in patients with lower-risk MDS. A clinical trial update on oral azacitidine in lower-risk MDS patients showed that approximately 40-50% of patients had improvements in their blood counts and/or in their requirements for red blood cell transfusions. This is an important preliminary study that has set the stage for the study that will determine whether oral administration of azacitidine will be FDA approved for treatment of lower-risk MDS.
What do you think patients would most want to know about the state of MDS treatment as it was presented and discussed at ASH 2012?
As we get better at discovering and defining the genetic underpinnings of MDS, the next step will be to see if patients with certain genetic abnormalities are more likely to respond to some drugs than other ones. We are becoming more sophisticated at selecting patients who are more likely to respond to a certain drug.
There were presentations on new genetic abnormalities found in MDS, some validating findings previously reported and some identifying new findings. One of the major ones was an international collaboration reporting on over 700 patients with MDS, MDS/MPN overlap, or AML that had evolved from MDS. This study found that 20% of the patients had a genetic abnormality (called SETBP1) that happens to be the same found in a rare congenital syndrome of infants born with retardation and skeletal abnormalities. This was typical of discoveries in MDS presented at ASH 2012.