Inclusion Criteria:
1. Patients aged 18 to 75 years.
2. Confirmed diagnosis of primary myelofibrosis (PMF) according to World Health Organization (WHO) diagnostic criteria, or secondary myelofibrosis (SMF), including post-polycythemia vera myelofibrosis (post-PV MF) and post-essential thrombocythemia myelofibrosis (post-ET MF), according to International Working Group for Myelofibrosis Research and Treatment (IWG-MRT) criteria.
3. Patients must meet at least one of the following disease risk criteria:
Intermediate-2 or high-risk disease according to the Dynamic International Prognostic Scoring System Plus (DIPSS-plus).
Intermediate-1 risk disease according to DIPSS-plus with at least one of the following adverse features:
Red blood cell transfusion dependence.
Unfavorable cytogenetic abnormalities, including trisomy 8 (+8), monosomy 7 or deletion 7q (-7/del(7q)), isochromosome 17q \[i(17q)\], inversion 3 \[inv(3)\] or abnormalities involving 3q21, monosomy 5 or deletion 5q (-5/del(5q)), deletion 12p \[del(12p)\], or 11q23 rearrangements.
Platelet count ≤100 × 10\^9/L.
High-risk molecular abnormalities associated with adverse prognosis, including ASXL1, EZH2, IDH1, IDH2, SRSF2, U2AF1, or TP53 mutations.
4. Patients must have completed transplantation eligibility assessment and be considered suitable candidates for allogeneic hematopoietic stem cell transplantation (allo-HSCT). Either peripheral blood or bone marrow stem cell grafts are permitted. Donor type is not restricted.
5. Eastern Cooperative Oncology Group (ECOG) performance status ≤2.
6. Estimated life expectancy ≥3 months.
7. Ability to understand the study requirements and provide written informed consent.
8. Ability to receive oral gecacitinib, including the ability to swallow tablets without clinically significant gastrointestinal absorption impairment.
9. No active severe infection at initiation of study treatment. Patients with infections may be eligible after adequate infection control.
10. Patients previously receiving gecacitinib for myelofibrosis may be enrolled if they satisfy all eligibility criteria and have no history of treatment failure, severe unacceptable gecacitinib-related toxicity, or unresolved grade ≥3 gecacitinib-related adverse events. A washout period is not required for patients continuing gecacitinib treatment.
11. Previous myelofibrosis-directed therapies, other than ongoing gecacitinib, must be discontinued at least 7 days or 5 drug elimination half-lives (whichever is longer) before initiation of study treatment on Day -14. Concomitant administration of other JAK inhibitors with gecacitinib is not permitted. Short-term hydroxyurea bridging therapy may be permitted if discontinued before Day -14 in accordance with the washout requirements.
12. Previous splenectomy is permitted.
13. Women of childbearing potential must have a negative pregnancy test before enrollment and agree to use effective contraception during the study and for 6 months after the last dose of gecacitinib. Male participants must agree to use effective contraception according to the protocol.
Exclusion Criteria:
1. Previous allogeneic hematopoietic stem cell transplantation.
2. History or presence of blast-phase myeloproliferative neoplasm at screening, defined as: blast phase: ≥20% blasts in peripheral blood or bone marrow.
3. Uncontrolled active infection requiring intensive intravenous antimicrobial treatment or hospitalization. Patients with stable, adequately controlled chronic infections may be considered eligible according to protocol-defined conditions.
4. Clinically significant uncontrolled infection with hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV). Patients with controlled chronic infections may be eligible if they meet protocol-defined conditions, including:
HBV: appropriate antiviral management without evidence of active hepatitis. HCV: no acute hepatitis or hepatic decompensation, with acceptable liver function.
HIV: stable antiretroviral therapy, undetectable HIV viral load, and CD4 count ≥350 cells/μL.
5. Requirement for concomitant strong CYP3A4 inhibitors that cannot be appropriately managed through gecacitinib dose adjustment, monitoring, or substitution in accordance with the protocol.
6. Significant hepatic impairment, including any of the following:
AST, ALT, or alkaline phosphatase ≥3 × the upper limit of normal (ULN). Direct bilirubin \>2.0 mg/dL. Total bilirubin \>1.5 × ULN.
7. Renal impairment with creatinine clearance ≤60 mL/min, calculated using the Cockcroft-Gault formula.
8. Severe cardiac dysfunction, including New York Heart Association (NYHA) class III-IV heart failure or left ventricular ejection fraction (LVEF) \<40%.
9. Other severe organ dysfunction that, in the investigator's judgment, would preclude safe transplantation or administration of the study treatment.
10. History of severe hypersensitivity to gecacitinib or any of its excipients.
11. Previous gecacitinib treatment failure, including inadequate clinical response or persistent disease progression despite adequate treatment, requiring alternative myelofibrosis-directed therapy, as determined by the investigator.
12. History of severe unacceptable gecacitinib-related toxicity, or unresolved grade ≥3 gecacitinib-related adverse events at screening.
13. Pregnancy or breastfeeding, or unwillingness to use effective contraception during the required study period.
14. Inability to provide informed consent or serious psychiatric, cognitive, social, or behavioral conditions that may substantially impair protocol adherence, completion of follow-up, or safety assessments.
15. Inability to take oral study medication, including swallowing difficulties, severe gastrointestinal malabsorption, persistent vomiting, or other conditions likely to significantly impair oral drug absorption.
16. Any other condition that, in the investigator's opinion, may substantially increase study-related risks, compromise adherence, or interfere with the interpretation of study results.
