Efficacy and Safety of XTD Regimen (Selinexor, Thalidomide and Dexamethasone) in Adult Patients With Relapsed/Refractory LCH

• Selinexor (Drug): The combined treatment period includes 12 cycles: receiving Selinexor (60mg, D1, 8, 15, 22), Thalidomide (100mg, D1-28), and Dexamethasone (40mg, D1, 8, 15, 22) as oral treatment, with each cycle lasting 28 days, for a total of 12 cycles of combined treatment, or until disease progression, death, or occurrence of intolerable toxicity. Alternatively, until disease progression, death, or occurrence of intolerable toxicity.
• Thalidomide (100mg) (Drug): The combined treatment period includes 12 cycles: receiving Selinexor (60mg, D1, 8, 15, 22), Thalidomide (100mg, D1-28), and Dexamethasone (40mg, D1, 8, 15, 22) as oral treatment, with each cycle lasting 28 days, for a total of 12 cycles of combined treatment, or until disease progression, death, or occurrence of intolerable toxicity. Alternatively, until disease progression, death, or occurrence of intolerable toxicity.
• Dexamethasone (Drug): The combined treatment period includes 12 cycles: receiving Selinexor (60mg, D1, 8, 15, 22), Thalidomide (100mg, D1-28), and Dexamethasone (40mg, D1, 8, 15, 22) as oral treatment, with each cycle lasting 28 days, for a total of 12 cycles of combined treatment, or until disease progression, death, or occurrence of intolerable toxicity. Alternatively, until disease progression, death, or occurrence of intolerable toxicity.

Primary outcomes

• PFS [From enrollment to the end of treatment at 8 weeks]: PFS defined as the time from XTD initiation to first documented disease progression, relapse after XTD, death from any cause, or last follow-up.

Secondary outcomes

• ORR [From enrollment to the end of treatment at 8 weeks]: The overall response rate (ORR) was defined as the cumulative proportion of patients attaining either a complete response (CR) or partial response (PR) .
• OS [From enrollment to the end of treatment at 8 weeks]: OS was measured from XTD initiation to death or last follow-up
• Adverse Events [From enrollment to the end of treatment at 8 weeks]: Toxicities were recorded and graded per National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.

Other outcomes

• Correlation between the positivity of NGS in MAPK pathway and therapeutic efficacy/PFS [From enrollment to the end of treatment at 8 weeks]: Correlation between the positivity of NGS in MAPK pathway and therapeutic efficacy/PFS
• Fact-G [From enrollment to the end of treatment at 8 weeks]: The score of Functional Assessment of Cancer Therapy - General

Sex: All, ages: 18 Years to 80 Years

Inclusion Criteria:

* Organ pathology confirmed diagnosis of LCH;
* Age 18 years or older;
* Multi-system involvement, or single system with multiple lesions;
* Disease not relieved after receiving at least one systemic treatment, or disease relapsed after improvement;
* ECOG performance status score ≤2;
* Clinical physician determines suitability for this treatment protocol;
* Subjects can understand the study protocol and are willing to participate in this study, providing written informed consent.

Exclusion Criteria:

* Single system single lesion LCH
* Underwent major surgery within 4 weeks prior to the first administration of the study drug;
* Underwent radiotherapy within 4 weeks prior to the first administration of the study drug;
* History of myocardial infarction within the past year; suffers from New York Heart Association (NYHA) class 3 or 4 congestive heart failure, or has a history of NYHA class 3 or 4 congestive heart failure, unless left ventricular ejection fraction (LVEF) ≥ 50% in the echocardiogram (ECHO) screening performed within 1 month before entering the study;
* Pregnant or breastfeeding women (women of childbearing age with positive pregnancy test at baseline or who have not undergone pregnancy testing. Postmenopausal women must have been menopausal for at least 12 months);
* Abnormal liver and kidney function: creatinine level ≥176.8μmol/l (2mg/dl), transaminase and bilirubin levels more than 2 times the upper limit of normal (for LCH patients with liver involvement, transaminase levels more than 10 times and bilirubin levels more than 3 times the upper limit of normal);
* Severe hematological abnormalities: absolute neutrophil count less than 1 × 10\^9/L, platelet less than 50×10\^9/L;
* Presence of uncontrolled infections;
* Any other circumstances that the investigator believes to be inappropriate for the patient to participate in this trial;