ASH 2023 | Minimal clinically important difference in patient-reported MF-associated outcomes: MANIFEST arm 3

So I was pleased to present an analysis at this year’s ASH regarding the arm three, or the JAK inhibitor naive arm, for the MANIFEST study of ruxolitinib plus pelabresib, and taking a deeper dive as it relates to symptoms and symptom response. As we assess symptoms, we use the MPN-SAF, which looks at several different individual symptoms from a 0 to 10 scale. And there are many ways of looking at these sort of data. Historically, they’ve been looked at as a total symptom score and a change in the total symptom score. Now, many of us have felt that this is probably an insensitive kind of measurement of change, realizing that there’s probably clinically meaningful changes that occur before reaching a, let’s say, 50% reduction in the total symptom score for a range of reasons. You know, one, individual symptoms can have a different impact for an individual, you know, a higher burden of pruritus, for example, may be more problematic for a patient than, let’s say, night sweats or some other piece. You know, we’re truly quantifying the subjective. 

So in this analysis, we anchored with a patient’s global impression of change. And we were able to try to look at the minimally clinically significant difference in terms of symptoms, and saw that really a one and a half to two point difference or decrease in an individual symptom really might be very clinically meaningful for that individual patient. And that matches with much of the initial analysis we had done when these symptom scores were developed -Dr Amylou Dueck, a statistician at Mayo Clinic, and I who have partnered on these things. So I think we need to listen to our patients as it relates to symptom response, but I think there’s a lot of granularity in these data and that at this year’s ASH, we’re looking at other areas such as absolute change and other ways of looking at these data beyond just total symptom score response.