At the 65th American Society of Hematology (ASH) Annual Meeting, Douglas Tremblay, MD, Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY discussed the prevalence and predictors of emergent thrombocytopenia following ruxolitinib treatment among patients with myelofibrosis (MF). 

“These data may guide the preferential use of alternative JAK inhibitors in patients who are at increased risk of developing treatment-related thrombocytopenia that would necessitate dose reduction or hold,” Tremblay and colleagues wrote. 

Transcript:

My name is Douglas Tremblay from Mount Sinai School of Medicine, New York, and I'm here at ASH 2023 where we're presenting among other research a project that evaluates the emergence of thrombocytopenia with ruxolitinib treatment. Ruxolitinib is the mainstay of treatment for myelofibrosis for many years, and one side effect that has been well described is hematologic toxicity, in particular thrombocytopenia, which can limit dosing and also can cause patients to discontinue. This was of some concern, but now it's become of more relevance now that there's the availability of additional [Janus kinase] (JAK) inhibitors that can be used and treat patients with thrombocytopenia safely. Now that there's the availability of other JAK inhibitors, it raises the question of if we can predict which patients treated with ruxolitinib with myelofibrosis to go on to develop thrombocytopenia, maybe we can tailor the approach to myelofibrosis patients with their JAK inhibitor choice in the front line.

To explore this question, we put together a cohort of around 250 patients with myelofibrosis at Mount Sinai and Moffitt Cancer Institute, and we asked the question, what are the predictors of moderate or severe thrombocytopenia in patients with a baseline platelet count above 100,000 who are initiated on ruxolitinib? We really looked at the time point of 3 months or 6 months to try to isolate thrombocytopenia that emerges with ruxolitinib treatment rather than disease-related thrombocytopenia which can occur further along in the disease course. What we found is that around 50% of patients do end up having a platelet count that is between 50 and 100,000, and when we looked at particular predictors, we were not surprised to find our main finding that baseline thrombocytopenia, particularly a platelet count of 100 to 150, or even 150 to 200,000, is really associated with the highest risk of having treatment-emergent thrombocytopenia.

No individual mutations were predictive of emergence of moderate or severe thrombocytopenia, although additional analysis is ongoing trying to see if co-occurring mutations or groups of mutations can add prognostic and predictive values to this. We also were really surprised by a few other features of this, in that around 70% of the patients or so, 77% were underdosed with ruxolitinib as it relates to the FDA label based on platelet count, which suggests that maybe some of these patients are not getting full dose ruxolitinib, which is of concern because that has really been associated with maybe sub-optimal efficacy as well, but also highlights the concern among clinicians around thrombocytopenia in this group. Using this data moving forward, I think it's important to understand that maybe thrombocytopenic patients who are at risk of developing severe or moderate thrombocytopenia and maybe preferentially forward it to a different JAK inhibitor in the frontline setting.

Source:

Tremblay D, Schwabkey Z, Riazat-Kesh Y, et al. Prevalence and prediction of ruxolitinib treatment emergent thrombocytopenia in myelofibrosis. Presented at the 2023 ASH Annual Meeting: December 9-12, 2023. San Diego, CA. Abstract 1830