Background Currently, treatment for myeloid sarcoma (MS) primarily follows protocols of AML including standard chemotherapy and hematopoietic stem cell transplantation (HSCT), while most patients have a poor outcome. Sorafenib, a multitargeted tyrosine kinase inhibitor (TKI), has demonstrated promising antileukaemic activity in AML. We previously showed sorafenib combined with conventional therapies is effective and safe for refractory central nervous system leukemia (CNSL). Therefore, this study aims to evaluate the efficacy and safety of sorafenib combined with standard chemotherapy in adult patients diagnosed with MS.Methods In this multicenter, cohort study, the study population came from our three randomized controlled trial (NCT05404516, NCT02474290 and NCT03620955). Patients who met the following criteria were enrolled: (a) aged 18–65 years; (b) diagnosed with MS; (c) Eastern Cooperative Oncology Group Performance Status: 0-2. Patients were excluded from the study if they met any of the following criteria: (a) diagnosed with acute promyelocytic leukemia; (b) presence of significant uncontrolled or active cardiovascular, pulmonary, hepatic, or nephrotic disease. Patients who received standard chemotherapy were allocated to the control group, and those who received sorafenib combined with standard chemotherapy were allocated to the sorafenib group. For control group, patients received one cycle of induction therapy with idarubicin (12 mg/m² on days 1-3) plus cytarabine (100 mg/m² on days 1-7), followed by one cycle of idarubicin (8 mg/m² on days 1-3) plus cytarabine (2 g/m² q12h on days 1-3) and two cycles of high-dose cytarabine consolidation therapy (2 g/m² q12h on days 1-3). For sorafenib group, patients were treated with chemotherapy plus sorafenib at 400 mg twice daily on days 8-21 for induction cycle, and on days 1-21 for each consolidation, and as maintenance for 12 months. Allogeneic HSCT were implemented based on the complete remission status and donor availability after 4 cycles of therapy. The primary endpoint was the overall survival (OS), the secondary endpoints were complete remission (both intramedullary and extramedullary)rate (CR) after 4 cycles of treatment, event-free survival (EFS), cumulative incidence of relapse (CIR), and adverse events (AEs).Results A total of 71 patients with newly diagnosed MS were enrolled in this study, consisting of 4 cases with isolated MS, 43 with MS with concurrent AML and 24 with extramedullary relapse of AML including relapse in the posttransplant setting.32 cases were allocated to the control group and 39 cases to the sorafenib group. There were no significant differences between the two groups in age, gender, bone marrow blasts, cytogenetics, subtype of MS at diagnosis and HSCT. After 4 cycles of treatment, the complete remission(both intramedullary and extramedullary) rate was significantly higher in sorafenib group than that in control group (76.5% vs 40.0%, p = 0.045). With a median follow-up of 45.4 months(range, 1.1-97.9 months), sorafenib group showed a significantly higher 3-year OS than control group (62.3% vs 25.6%, p = 0.004). Sorafenib combined with standard chemotherapy also significantly improved 3-year EFS (66.6% vs 32.1%, p < 0.001) and decreased 3-year CIR (35.0% vs 53.80%, p = 0.028) when compared with chemotherapy alone. Multivariate analysis identified allogeneic HSCT (HR = 0.20, [95% CI: 0.07-0.56], p = 0.002) and sorafenib plus chemotherapy (HR = 0.33, [95% CI: 0.13-0.83], p = 0.019) as independent favorable prognostic factors for OS. Rates of grade 3 or higher hematologic toxicities were similar in sorafenib and control group, with neutropenia (94.3% vs 89.6%), thrombocytopenia (95.6% vs 92.4%) and febrile neutropenia (83.5% vs 78.5%), respectively. The most common grades 3 or higher non-hematologic toxicities in sorafenib and control group were pneumonia (16.2% vs 20.2%), anorectal infection(14.9% vs 8.6%), diarrhea (20.8% vs 15.2%) and rash (14.1% vs 5.2%).Conclusions Addition of sorafenib to standard chemotherapy might provide a new, effective, and generally well tolerated treatment option for adult patients with MS.

Keywords: Sorafenib, Standard chemotherapy, Myeloid sarcoma, Overall survival

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2025
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