Impact of Cytopenias on Treatment With Ruxolitinib Versus Best Available Therapy for SR-aGVHD

By Dustin Samples - Last Updated: February 21, 2023

The oral Janus kinase (JAK)1/JAK2 inhibitor ruxolitinib (RUX) was recently evaluated against the best available treatment (BAT) in the open-label phase 3 REACH2 trial of patients aged 12 years and older with grade II-IV steroid-refractory acute graft-versus-host disease. Though RUX was associated with a higher response rate than BAT, some patients developed clinically relevant cytopenias.

In a post hoc analysis of the REACH2 results, researchers assessed the effects of cytopenias, including platelet count (PLT), hemoglobin (Hgb), white blood cell count (WBC), and absolute neutrophil count (ANC), on treatment response. Laboratory values were assessed at baseline, each week through week 8, and then every 4 weeks through week 24.

For the analysis, the authors report, “Overall response rate (ORR [complete response + partial response]) at Day 28 and durable response at Day 56 among Day 28 responders were assessed in PLT, Hgb, WBC, ANC, and any cytopenia subgroups defined by the presence (low) or absence (not low) of ≥1 low PLT, Hgb, WBC, or ANC measure between baseline and Wk 4.”

A total of 302 patients were included in the analysis (RUX, n=152; BAT, n=150). No significant differences in PLT or Hgb were observed between patients treated with RUX and BAT at any time point, although both groups experienced similar drops in count over the first 4-8 weeks of treatment. Both treatment groups experienced similar drops in WBC and ANC but remained lower at week 24 in the RUX group.

Regardless of the presence or absence of cytopenia, ORR was higher in the RUX group at day 28, and durable responses were observed at day 56 in all day 28 responders across all cytopenia subgroups. However, the researchers observed that “Median duration of response was numerically longer with RUX vs BAT for all PLT and Hgb subgroups as well as the low WBC and not low ANC subgroups.”

These results demonstrate that regardless of the presence or absence of cytopenias, RUX achieved better ORR than BAT at day 28, and durable responses were observed at day 56. The similar incidence of cytopenias across both the RUX and BAT groups could indicate a myelosuppressive effect of aGVHD rather than anything inherent to the treatments.

Socié G, Bhatt V, Galvin J, et al. Impact of Cytopenias in Patients Treated with Ruxolitinib Versus Best Available Therapy for Steroid-Refractory Acute Graft-Versus-Host Disease: A REACH2 Post Hoc Analysis. Abstract #344. Presented at the 2023 Tandem Meetings of ASTCT and CIBMTR; February 15-19, 2023; Orlando, FL.

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