Published on January 7, 2014
Dr. Claire Harrison, a leading MPN expert, provides an analysis of the COMFORT-I and COMFORT-II trials, which focus on evaluating the use of a JAK inhibitor, ruxolitinib, in treating people with myelofibrosis. Dr. Harrison explains how the studies shed new light on treatment safety and efficacy, while also revealing more about the drug's potential impact on quality of life and survival.
Made possible through an educational grant from the Patient Empowerment Network.
Transcript | The COMFORT Trials: What Is the Impact on Survival?
With therapies that we have now or others that may be emerging, does that give us new hope?
Yeah, I think so. So really a lot of data with regard to ruxolitinib, Jakafi, the first approved JAK inhibitor, at this meeting. Further analysis from the large Phase III studies, the COMFORT trials, ongo—so the phase, the COMFORT?I, the year three data is presented by Ruben Mays at this meeting showing ongoing efficacy, no new safety concerns.
And interestingly, as you are aware, a challenge in using this drug is anemia and low platelet counts but no emerging feature with this. This is something we see in the first three months and tends to gradually resolve either on its own or with dose modification—so no new safety signal.
We're not presenting new safety data or new outcome data for COMFORT?2, which was a European sister trial at this meeting. What we are presenting is a couple of things. So first, an analysis with a different control group looking at survival, so that's presented by Francesco Passamonti, looking at population of patients diagnosed at the same time, strengthening what we already understand about survival benefit.
Second, a pooled analysis, a pooling together the COMFORT trial patients and analyzing then what was the benefit in terms of survival and doing an RFSSD analysis, which negates the effect of crossover. Please don't ask me to explain the statistics, but it's a very robust tool that is used by the FDA and the European Medicines Agency and allowed in other disease settings where we have crossover trials for ethical reasons, strengthening again the survival benefit data.
But also interestingly there was an analysis in this data looking at what are the impacts upon likely survival. The usual culprits are included there, so age, hemoglobin, white cell count, etc. But for the first time, we see spleen size being implicated. So we'd always wondered about spleen size as an end point in these studies, and here we see in this analysis a couple of things.
First, that the bigger the baseline spleen size the less likely the duration of survival. But, secondly, the greater the degree of spleen reduction the greater the likely survival benefit. So that's very interesting in terms of potentially where should we as clinicians where we're looking to use this drug above and beyond improving quality of life to prolong survival, maybe a little clue as to how our patients might be doing when we're examining spleen.
Alessandro also presents data from the COMFORT?II patients assessing the story that has emerged over the last year about molecular risk and myelofibrosis. If you remember at last year's ASH and recently published in Leukemia, he presented data from four genes, ASXL1, EZH?2, SRSF2 and the IDH1/2 gene, showing that if you have a mutation in one or more of these, you're so?called molecular high risk, greater risk of developing leukemia and worse overall survival.
And we were able to analyze this in the COMFORT?II cohorts of patients and show that actually ruxolitinib treatment benefits patients no matter what their molecular status is. Many patients, of course, won't know what their molecular status is for these markers, but the data is interesting. So ruxolitinib would benefit patients no matter what and appears to bring the likely survival of the molecular high?risk patients who have at least one of these mutations back to the lower risk category. So we're learning more about ruxolitinib.