Hi, this is Michael Mauro. I am from Memorial Sloan Kettering Cancer Center in New York. I am a professor of medicine and leader of the myeloproliferative disorders program here reporting to on behalf of ManagingCML.com. We are talking about the SIMPLICITY study, perhaps better known by its full name “Studying First Line Treatment of CML in a Real-world Setting,” and the SIMPLICITY study is supported by Bristol-Myers Squibb and a company by the name of ICON, and the ClinicalTrials.gov identifying number is NCT01244750. So, what is the SIMPLICITY study? This is an observational study of newly diagnosed CML patients treated with TKIs. The design is to follow patients in a smaller cohort retrospectively from those beginning in 2008 who were prescribed imatinib, and then starting in 2010 patients who were prescribed either imatinib, nilotinib, or dasatinib, essentially after the drugs were FDA approved. The design is to follow patients through 5 years, and I am glad to report that we fully accrued, and the total number is just shy of 1,500 patients, and this is a trial that is run in both US and European Unions, so this is very broad effort across the globe to study some very important questions. So, again, why an observational study in CML? We clearly have a large volume of data for CML patients under treatment for TKIs from large studies such as the IRIS trial using imatinib and very long-term followup in that trial and as well now completed data from the DASISION trial, primary treatment of CML patients with dasatinib, and continued followup of the ENESTnd trial, primary treatment with nilotinib. Those were clinical trials with certain discrete entry criteria and performed in certain sites, etc., with some limitations. And a real-world observational study might be a better judge of a number of different questions we might have regarding the treatment for chronic phase CML, namely – How are the drugs prescribed? How do people fare? What kind of toxicity do they have? How are they monitored? How do we used cytogenetic molecular testing? What kind of changes in therapy are made whether it is due to response or to toxicity issues? What kind of complications carry certain implications, particularly some of the questions we have currently regarding select toxicities? And what is the long-term outcome? A very important effort, I think, will be significantly complementary to the data we have with the IRIS, ENESTnd, and DASISION trial. So, what have we learned so far? We have already reported somewhat on the SIMPLICITY trial as we have now fully accrued, and one of our first questions was early on we would be able to observe how testing was deployed in the chronic-phase CML. Unfortunately we have learned that testing is done somewhat less than we would expect based on both European and US guidelines. We have previously reported that with regards, to cytogenetic response, only half of patients have testing in the first year, and of those, 40% or so only have one test done, and that is clearly not enough with regard to cytogenetic testing in year one. That being said, there is slightly more testing ongoing in the European Union in academic centers which was observed in the trial. The study also looked at molecular response, and here we are doing somewhat better with upwards of 88+% of patients having molecular testing done in the first year, but if subsequent analysis really was striking saying that only a third of patients had any tests done in the first three months, which is really inadequate because we know early molecular response is important, and even to start the early cytogenetic response was predictive of long-term good outcome for CML patients. What were the predictors we might have seen for patients having testing done a bit more frequently? Older patients greater than 65 years of age, patients seen at academic centers, and patients who have switched therapy were more likely to be tested. So, testing really has taught us already some gaps and some changes we need to make in our practice. What about switching therapy? We already reported on this as well, and we see that there is a bit more switching ongoing in the US compared to the European Union, but it is not different than what would expect, about 20% to 30% within year one. Patients are mainly switched due to intolerance, although some are switched for resistance as well and those encompass the main groups. Interestingly, nilotinib seems to be the drug that is most rapidly identified to be an issue with intolerance and is thus discontinued, and when we look at what drugs are used as second therapy after imatinib, with this question, nilotinib is somewhat preferred in the European Union whereas dasatinib is somewhat preferred in the US, but overall, dasatinib is the most common second-line therapy administered, at least in the SIMPLICITY study. So, there are some important lessons already learned regarding how we manipulate therapy given the treatment armamentarium we have for CML. Most recently, we have begun to examine some of the important questions we have regarding select toxicities, and just at the 2015 European Hematology Association Meeting is ongoing, we have some studies, and one of them would be regarding cardiovascular hospitalizations, and with this question, we have seen not surprisingly that perhaps older patients, more male predominance, and a bit more in the US, patients are having cardiovascular hospitalizations mainly for cardiovascular ischemia, for angina, heart failure, and typical syndromes we might expect, and perhaps as one might have suspected, nilotinib patients have a somewhat higher rate of cardiovascular hospitalization than patients with imatinib or dasatinib. There are many questions already examined, but many questions still to answer, and the goal of this large effort, again a large observational study of nearly 1,500 patients in the European Union and US, will help us understand complementary to what we know for the long-term outcomes in clinical studies run through industry of imatinib, nilotinib, and dasatinib. What do we see with regard to long-term outcome, long-term benefits, patterns of testing, manipulation of therapy, ie, switch, perhaps discontinuation, and importantly what we do learn regarding best management of toxicity and adverse events that patients may experience? So, stay tuned for further data from the SIMPLICITY trials. We will continue to follow over the long term and answer some important questions remaining for chronic-phase patients with CML.
ClinicalTrials.gov Identifier NCT01244750. Studying First Line Treatment of Chronic Myeloid Leukemia (CML) in a Real-world Setting (SIMPLICITY) https://clinicaltrials.gov/ct2/show/NCT01244750