Efficacy and Safety of Doxorubicin–Etoposide–Methylprednisolone ( DEP )‐Based Regimens in Haemophagocytic Lymphohistiocytosis: A Systematic Review and Meta‐Analysis

Background Haemophagocytic lymphohistiocytosis (HLH) is a rare but severe hyperinflammatory syndrome caused by uncontrolled immune activation. Etoposide‐containing regimens are established in paediatric HLH, but evidence in adults remains limited. Doxorubicin–etoposide–methylprednisolone (DEP)‐based regimens have shown promising results; however, their efficacy and safety have not been systematically evaluated. We conducted a systematic review and meta‐analysis of DEP‐based regimens in patients with HLH. Methods Following PRISMA guidelines, we searched PubMed, the Cochrane Library and Embase through February 2026, with no language restrictions. We used random‐effects proportional meta‐analyses to estimate 4‐week overall response rate (ORR), complete response (CR), partial response (PR) and overall survival (OS). Sensitivity analyses assessed the influence of potentially overlapping cohorts and of individual study arms. Results Ten study arms from seven studies comprising 320 patients were included; all studies were conducted in China. Pooled ORR, CR and PR were 80% (95% CI, 75%–86%), 29% (95% CI, 23%–35%) and 49% (95% CI, 40%–57%), respectively, and were stable in sensitivity analyses. Pooled OS from four studies (164 patients) was 41% (29%–53%). Initial therapy achieved a higher CR than salvage therapy (39% vs. 24%; p = 0.0104), while ORR and PR were comparable. Response rates were consistent across age groups, HLH subtypes and regimen variations. Toxicity was generally manageable, with infection representing the most frequent adverse event. Conclusion DEP‐based regimens are associated with high response rates in HLH, predominantly in the relapsed and refractory setting. The higher CR rate observed with initial use compared with salvage here is likely to be confounded by indication and does not support frontline use. Prospective multi‐centre comparative studies are required to determine the efficacy and tolerability of DEP‐based therapy.