Gecacitinib, a novel therapeutic agent, has demonstrated superior efficacy in reducing spleen volume in patients with intermediate-2 or high-risk myelofibrosis compared to hydroxyurea (HU), according to results from a recent clinical trial. The study, which randomized 105 participants, showed a significantly higher spleen volume reduction rate (SVR35) at 24 weeks in the gecacitinib group (64.8%) compared to the HU group (26.5%), with a difference of 36.5% (95% CI: 19.0–53.9%; P = 0.0002). These findings suggest a potential new treatment option for patients with myelofibrosis.
Key Efficacy Outcomes
The trial's primary endpoint, SVR35 at 24 weeks, was significantly in favor of gecacitinib. Secondary endpoints also showed notable benefits. At 12 weeks, the SVR35 was 53.5% for gecacitinib versus 20.6% for HU (P = 0.0017). The best overall spleen response rate reached 81.7% in the gecacitinib group, markedly greater than the 32.4% observed in the HU group (P < 0.0001). The median percentage of the largest spleen volume reduction from baseline was 51.7% in gecacitinib-treated patients compared to 30.0% in the HU group.
In terms of total symptom score (TSS), 62.0% of gecacitinib patients reported a TSS50 (≥50% reduction in TSS) at week 24, compared to 50.0% in the HU group (P = 0.2065). Furthermore, 47.9% of gecacitinib patients achieved both SVR35 and TSS50 responses at week 24, versus 20.6% in the HU group (post-hoc analysis).
Impact on Anemia and Platelet Levels
Gecacitinib also showed promise in improving anemia, a common complication of myelofibrosis. One of six transfusion-dependent gecacitinib patients at baseline became transfusion-independent post-treatment, whereas none in the HU group achieved this (P = 0.4386). Among non-transfusion-dependent patients with hemoglobin (HGB) ≤100 g/L at baseline, 31.0% in the gecacitinib group experienced an increase of at least 20 g/L in HGB post-treatment, compared to 15.0% in the HU group. "Gecacitinib demonstrated a positive effect compared to HU, as indicated by the mean absolute change in HGB relative to baseline at each visit, particularly at week 24 (1.27 g/L vs −3.50 g/L)," the researchers noted.
Interestingly, despite having lower initial platelet levels, the gecacitinib group exhibited less fluctuation in platelet levels, and from week 4 onward, the mean platelet levels surpassed those of the HU group (-93.28 × 109/L vs -182.56 × 109/L).
Safety Profile and Adverse Events
The safety analysis revealed that adverse event occurrence was 98.6% in the gecacitinib group, with ≥grade 3 AEs in 49.3%, while the HU group reported 100% occurrence with 64.7% at ≥grade 3. The incidence of serious AEs was 26.8% for gecacitinib and 41.2% for HU. Common grade ≥3 treatment-emergent adverse events (TEAEs) included anemia (26.8% in gecacitinib vs 44.1% in HU) and thrombocytopenia (15.5% vs 32.4%).
Study Design and Patient Population
The study enrolled patients with intermediate-2 or high-risk myelofibrosis. Baseline characteristics were generally balanced between the two groups, with the exception of a higher proportion of patients with grade 3 bone marrow fibrosis in the gecacitinib group (59.2% vs 44.1%). The average age of the patient was 63.1 years, and the majority were diagnosed with primary myelofibrosis (PMF) (73.3%).
Implications for Myelofibrosis Treatment
These results suggest that gecacitinib may offer a more effective treatment option for patients with myelofibrosis, particularly in reducing spleen volume and potentially improving anemia, with a manageable safety profile. Further studies are warranted to confirm these findings and explore the long-term benefits of gecacitinib in this patient population.
