Gecacitinib for cGVHD: Safety and Efficacy in Patients After ≥2 Lines of Prior Therapy

Inclusion criteria

• Voluntarily Signed informed consent and aged ≥18 years
• Undergone nonmyeloablative, myeloablative, or reduced-intensity allo-HSCT using bone marrow, peripheral blood stem cells, or umbilical cord blood from any donor source
• Confirmed myeloid and platelet engraftment: ANC >1.0×10⁹/L and platelet count >25×10⁹/L; no hematopoietic growth factors or blood product transfusions within 7 days before screening
• Clinically diagnosed moderate-to-severe cGVHD according to the 2014 NIH
• Received 2-5 prior systemic cGVHD therapies with persistent disease
• ECOG PS score of 0-2
• Able to swallow tablets
• Concomitant use of non-interacting immunosuppressants permitted

Exclusion criteria

• Recurrence of malignancy or loss of full donor chimerism
• Concurrent use of other JAK inhibitors, mesenchymal stem cells, or belumosudil (Eligible if discontinued for >8 weeks post-aGVHD treatment or stopped JAK inhibitors for cGVHD due to side effects.)
• Severe pulmonary cGVHD (FEV1 ≤39% or NIH lung symptom score of 3)
• Post-transplant lymphoproliferative disease
• Significant abnormalities affecting safety assessment, such as uncontrolled hypertension (SBP ≥160 mmHg or DBP ≥100 mmHg) despite ≤2 antihypertensives; ALT/AST >3×ULN; DBIL/TBIL >1.5×ULN; serum creatinine >1.5×ULN
• History of major cardiovascular events within 6 months.
• Arrhythmia requiring treatment at screening
• Gastrointestinal conditions impairing drug absorption
• Surgery within 4 weeks of screening with incomplete recovery
• Active/uncontrolled infections (viral, bacterial, parasitic, fungal) requiring treatment
• Active tuberculosis within 6 months
• Epilepsy or use of psychotropic/sedative drugs
• Pregnant/breastfeeding or unwilling to use contraception during and 4 weeks post-study
• Malignancy within 5 years (except the indication for transplant)
• Use of anticoagulants/platelet inhibitors (except low-molecular-weight heparin)
• Herbal medicine use within 1 week prior to enrollment
• Hypersensitivity to gecacitinib or its components
• Participation in another clinical trial within 4 weeks (or 5 half-lives of the previous study drug, whichever is longer)
• Deemed unsuitable by the investigator