This study aimed to investigate the efficacy and safety of venetoclax combined with dexamethasone and etoposide as a salvage therapy for hemophagocytic lymphohistiocytosis.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and aggressive disease with high mortality and poor prognosis. The HLH-94 and HLH-04 regimens are most commonly used, but approximately 30% of the patients remain unresponsive. Currently, there is no unified evidence-based salvage treatment. There is no unified salvage regimen. This study plans to enroll 20 patients with refractory and recurrent hemophagocytic lymphohistiocytosis. Subjects will receive venetoclax combined with dexamethasone and etoposide for 8 weeks.The safety was evaluated once a week, and the efficacy was evaluated once every 2 weeks. Overall response rate will be evaluated at 8 weeks. Patients were followed up every 3 months thereafter.

Inclusion Criteria:

• age ≥18 years old, expected survival time more than 3 months;
• met HLH-2004 diagnostic criteria；
• ECOG score 0-2；
• ECG QTcF interval: male ≤450ms, female ≤470ms;
• AST and ALT ≤3.0 ULN, TB ≤1.5×ULN；serum creatinine≤1.5×ULN，or CrCL ≥ 50mL/min；INR、APTT、PT ≤1.5×ULN；
• without pregnancy or lactation, and agree to contraception during and for at least 6 months after the study；
• signed informed consent.

Exclusion Criteria:

• patients with malignancies unrelated to HLH, except for fully recovered non-melanoma skin cancer and carcinoma in situ;
• patients participated in other clinical trials within 4 weeks；
• previously treated with Bcl-2 inhibitors；
• unable to take oral medication；
• history of substance abuse or patients with mental illness；
• severe infection；
• cardiovascular disease，NYHA II-IV；
• allergic to venetoclax or etoposide.