Several biomarkers evaluated at baseline and during treatment were identified that were associated with response to ruxolitinib among patients with steroid-refractory or steroid-dependent (SR/D) acute graft vs host disease (aGVHD).

The biomarkers identified by the exploratory analysis of the REACH2 trial, which was reported in the journal Blood, included cytokines, chemokines, cell types, and inflammatory proteins, as well as some patient characteristics.

The phase 3 REACH2 trial ( identifier: NCT0291326) randomly assigned patients with SR/D aGVHD to receive ruxolitinib or best available treatment (BAT). Blood was collected for biomarker analysis at baseline prior to the first dose of treatment, then on days 14, 28, 56, and 168 or at time of discontinuation. Data were available for 295 patients, including 242 with data for 6 or more biomarkers.

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The efficacy data of ruxolitinib was previously reported, in which the rates of overall response and overall survival were greater than that of BAT. In this analysis, 21 biomarkers were evaluated at baseline and day 14 of treatment.

There was a significantly higher levels between responders versus nonresponders at baseline and day 14 for interleukin (IL)-8, ST2, HGF, REG-3α, IL-6, IL-2Rα, TNRSF1A, and B-cell marker (all P<.01). On day 14, TIM-3, SPP1, PI3, and CXCL10 were also significantly different between responders and nonresponders.

These findings and independent patient characteristics were used to develop baseline and day 14 models to predict response to ruxolitinib. The baseline model overestimated probabilities <0.4. However, biased-corrected results from the day 14 model were similar to actual response rates.

“Low levels of most aGVHDs (before/after treatment) and immune cell markers (before treatment) positively affect the probability of response,” the authors concluded in their report. “Models (baseline and day 14) can help identify patient characteristics and biomarkers for improved response to ruxolitinib vs BAT.”

Disclosures: This research was supported by Novartis and Incyte. Please see the original reference for a full list of disclosures.

Socié G, Nierderweiser D, von Bubnoff N, et al. Prognostic value of blood biomarkers in steroid-refractory or steroid-dependent acute graft-versus-host disease: a REACH2 analysis. Blood. 2023;141:2771-2779. doi: 10.1182/blood.2022018579.