Gecacitinib Achieves Clinically Meaningful Spleen, Symptom, and Anemia Responses in JAK Inhibitor–Naive MF

In a post hoc analysis of the phase 3 ZGJAK016 study, the dual Janus kinase/activin receptor type 1 (JAK/ACVR1) inhibitor gecacitinib was found to induce clinically meaningful improvements in spleen volume, symptom burden, and anemia for patients with JAK inhibitor–naive myelofibrosis (MF) across all baseline anemia severities (mild, moderate, and severe) with an acceptable safety profile. Investigators conducted the exploratory analysis to further elucidate gecacitinib’s impact on anemia, a key prognostic indicator of MF. Gecacitinib’s efficacy was consistent across anemia severity, demonstrating a dual-directional regulation of baseline hemoglobin. Yi Zhang, of The First Affiliated Hospital, Zhejiang University School of Medicine, presented the data at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting.

In the double-blind, randomized ZGJAK016 trial, gecacitinib  led to a superior spleen response over hydroxyurea, with a trend toward improvement in constitutional symptoms and anemia associated with MF in patients not previously treated with a JAK inhibitor. For this post hoc analysis, Zhang and colleagues categorized the patients who were randomly assigned to the gecacitinib group into subgroups based on their hemoglobin levels: 47 patients (66.2%) had moderate to severe anemia (<100 g/L), 11 (15.5%) had mild anemia (100 g/L to lower limit of normal [LLN]),10 (14.0%) had normal hemoglobin (LLN to upper limit of normal [ULN]), and 3 (4.23%) had elevated hemoglobin (> ULN).

The primary end point was the proportion of patients with a reduction in spleen volume of 35% or more from baseline (SVR35) at week 24. Secondary end points included the proportion of patients with reductions of 50% or more in total symptom score (TSS50) and transfusion independence (TI) rate at week 24 (defined as no red blood cell transfusions and no hemoglobin level <80 g/L in the last 12 weeks before week 24. Patients missing week 24 hemoglobin data were classified as non-TI, with no imputation performed for missing values.)

At week 24, SVR35 and TSS50 rates were comparable across subgroups and consistent with those observed in the intention-to-treat population (ITT; n=71). Specifically, 64.8% of the ITT population achieved SVR35 at this time point (moderate/severe anemia, 59.6%; mild anemia, 81.8%; normal hemoglobin, 70.0%; elevated hemoglobin, 66.7%). The TSS50 rate was 62.0% in the entire ITT cohort (moderate/severe anemia, 57.4%; mild anemia, 90.9%; normal hemoglobin, 50.0%; elevated hemoglobin, 66.7%).

The TI outcomes were also significant. At baseline, 69% of the ITT population (49 patients)  were TI. By week 24, 36 of these patients (73.5%) maintained TI.

In the subgroup of patients with moderate/severe anemia, 57.7% (15 patients) were TI at week 24. This included 15 of 26 patients (57.7%) who were TI at baseline and maintained this status, as well as 8 of 22 (36.4%) patients who were non-TI at baseline but achieved TI at week 24.

By week 2, mean hemoglobin levels increased in all patient subgroups, with levels stabilizing in those with anemia and slightly decreasing—but remaining above 110 g/L—in patients who had normal baseline hemoglobin levels. Hemoglobin levels in patients who had elevated levels at baseline decreased toward the normal range. This bidirectional effect was most notable in two groups:

• Patients with post–polycythemia vera MF and elevated baseline hemoglobin, who exhibited the greatest decrease in hemoglobin toward the normal range
• Patients with baseline anemia, who showed a trend toward increase in hemoglobin

The researchers also noted a decrease in platelet counts by week 2, except in the hemoglobin-elevated subgroup, in which they remained stable.

Gecacitinib had a manageable safety profile, with an incidence of grade 3 or higher treatment-emergent adverse events (TEAEs) that was similar for patients with anemia and the ITT population, except for anemia of grade 3 of higher, which was slightly higher in the group with anemia (36.2% vs 26.8%). The incidence of TEAEs leading to discontinuation of treatment was comparable.

The efficacy and safety data support gecacitinib ’s potential role as a treatment for patients with JAK inhibitor–naive MF who have varying degrees of baseline anemia, offering a new possibility for a traditionally difficult-to-treat disease.