Long-term treatment continuation of gecacitinib in myelofibrosis patients after ruxolitinib failure

Abstract

Abstract Introduction To evaluate treatment continuation of gecacitinib in myelofibrosis (MF) patients after ruxolitinib failure, we conducted a post-hoc analysis of pooled data from two phase 2 single-arm studies: ZGJAK006 (ruxolitinib-intolerant MF) and ZGJAK017 (ruxolitinib-refractory/relapsed MF). Methods Study designs were previously published. This analysis included 84 patients (ZGJAK006: n=50; ZGJAK017: n=34) with long-term follow-up for treatment continuation. Results Among the 84 patients, the median age was 60 years (range 25–75), with 50 males (59.5%). Disease subtypes included primary MF (n=70), post-polycythemia vera MF (n=7), and post-essential thrombocythemia MF (n=7). Molecular profiling showed JAK2V617F mutations (n=56), CALR mutations (n=20; Type 1: n=10, Type 2: n=7, uncommon: n=3), MPL mutations (n=6), and triple-negative (n=3). Baseline hematologic parameters included a median hemoglobin level of 87 g/L (range 44–149) and median platelet count of 136×10⁹/L (range 48–951). The median time from initial diagnosis was 24.2 months (range 2.7–352.1), with a median prior ruxolitinib treatment duration of 14.1 months (range 1.5–90.5). Seventy-eight patients started gecacitinib at 100 mg BID, 4 at 150 mg QD, and 1 each at 200 mg QD and 100 mg QD. Thirty-nine patients (46.4%) entered a compassionate use program after study completion. As of June 25, 2025, with a median follow-up of 3.8 years, 31 patients (36.9%) remained on gecacitinib. The median treatment duration was 22.4 months (range 0.1–60.3) for the entire cohort; 23.0 months (range 0.1–53.0) for patients starting at 100 mg BID; 23.0 months (range 0.1–60.3) for ruxolitinib-intolerant patients; and 18.3 months (range 3.2-47.0) for ruxolitinib-refractory/relapsed patients. Additionally, regression analysis demonstrated that treatment duration was significantly positively correlated with the percentage reduction in spleen volume from baseline at week 24. ConclusionsGecacitinib demonstrates durable treatment continuation (median >18 months across subgroups) in MF patients after ruxolitinib failure. These long-term data support its viability as a therapeutic option for ruxolitinib-intolerant or refractory/relapsed MF patients.