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Dr Sudipto Mukherjee: Rethinking Clinical Management for Patients With ISM


Population-level data highlight varied risk profiles among patients with indolent systemic mastocytosis (ISM), highlighting the need for individualized treatment approaches, according to Sudipto Mukherjee, MD, PhD, MPH, a physician in the department of hematology and medical oncology at Cleveland Clinic.

A groundbreaking study led by Sudipto Mukherjee, MD, PhD, MPH, a physician in the department of hematology and medical oncology at Cleveland Clinic, sheds light on the diverse survival outcomes among patients with indolent systemic mastocytosis (ISM).

The findings underscore the need for further genomic research to better understand the underlying mechanisms driving disease progression and mortality in this patient population.


What are the potential implications of your findings and how might the identification of specific patient characteristics or disease features and mortality inform future approaches to managing patients with ISM?

I think these results are definitely eye opening and should be factored in for any clinical practitioner managing systemic mastocytosis patients in daily clinical practice. This is probably the first and the largest population-level data on survival in ISM in the US, and it is clearly telling us that the [ISM] diagnostic entity is not a homogeneous entity. In fact, it has a wide phenotypic spectrum, with certain patients at a higher risk of progression to advanced disease and with higher mortality. And we also know from our prior work that not all patients [with ISM] behave the same way. There is a certain subset of patients who have a pretty high symptom burden compared to those with a lower symptom burden. I think the focus is to be aware when counseling these patients that not all patients [with ISM] are the same. Specifically, that not all of them are going to have a clinically indolent course, meaning they will not have an asymptomatic or minimally symptomatic disease lasting for a decade or so. Some of them will definitely be progressed to advance disease sooner rather than later and the overall mortality, irrespective of whether you have evidence of disease progression or not, is definitely inferior compared to the general population.

So, having that awareness is important, because that should factor in how frequently and closely they need to be monitored. And second, we need to find out what there are the biological or are there any genomic underlying causes that can explain why some progress faster and some progress at a slower rate. So, I think a much more in-depth, genomic understanding of these subset of patients [with ISM] who progress faster or have higher mortality needs to be done. And this study should trigger those subsequent studies from happening.

We do have tyrosine kinase inhibitors that are approved for patients with [ISM]. And this population-level study does provide very significant evidence and an impetus to consider treating these patients [with ISM] with a tyrosine kinase inhibitor, because that may mitigate the development of complications down the line. It’s still too early, but it may hopefully extend survival, especially in the group of patients [with ISM] who we do see in our analysis who happen to have a significant mortality, even in the first few years following the diagnosis.

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