Meta-analysis of the Efficacy and Safety of Systemic Treatment for POEMS Syndrome

Background POEMS syndrome is a life-threatening plasma cell neoplasm with the main clinical manifestations of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes. The syndrome is rare and has a poor prognosis. Despite the increasing understanding of POEMS syndrome, the exact pathogenesis is not fully understood, and there is no standard treatment. Systemic therapy, including short-course induction therapy before autologous stem cell transplantation (ASCT) and ASCT, has been proposed as a potentially effective treatment. These therapies are designed to control disease progression, improve symptoms, and improve patient survival. Objective This study aims to evaluate the efficacy and safety of therapy of short-term induction regimens, including the combination of melphalan and dexamethasone (MD) regimen, immunomodulators (thalidomide or lenalidomide) combined with Dexamethasone (TD or RD regimens), and ASCT for POEMS syndrome patients, providing evidence-based medicine for clinical treatment. Methods Computer retrieval was conducted in PubMed, Embase, and the Cochrane Library, with the search period ranging from the establishment of the databases to May 2024. At the same time, other search methods were combined to collect randomized controlled trials (RCT), non-RCT, case-control studies, cohort studies, etc. on the systemic therapies for POEMS syndrome. Meta-analysis of single-arm rates, sensitivity analysis, and publication bias analysis were performed using Stata 15.1 software. Results Fourteen studies including 794 patients with POEMS syndrome were included in this study. The meta-analysis showed that the response rates for the MD regimen, immune modulators, and ASCT in treating POEMS syndrome were 0.800 (95%CI=0.715-0.874) for hematological responses, 0.872 (95%CI=0.751-0.962) for VEGF responses, 0.796 (95%CI=0.603-0.941) for neurological responses, 0.108 (95%CI=0.000-0.309) for grade 3 or higher adverse reactions, and 0.940 (95%CI=0.908-0.966) for survival to last follow-up. Subgroup analysis showed that the response rates for the three treatments were 0.806, 0.726, and 83.0% for hematological responses; 95.8%, 88.7%, and 80.0% for vascular endothelial growth factor (VEGF) responses; 1.000, 0.642, and 0.926 for neurological responses; and 1.000, 0.978, and 0.908 for survival to last follow-up. Sensitivity analysis showed that the results were robust and were not significantly affected by the exclusion of individual studies. The Egger's test was used to assess publication bias, and the results showed no publication bias for hematological response rates (P=0.777), VEGF response rates (P=0.981), neurological response rates (P=0.060), grade 3 or higher adverse reaction rates (P=0.117), survival to last follow-up (P=0.088), and recurrence rates at last follow-up (P=0.885) . Conclusion In systemic therapy for POEMS syndrome, the hematological response rate is good for all three types of treatment, with particularly high neurological response rates for the MD and ASCT regimens. However, the RD regimen has a lower incidence of grade 3 or higher adverse reactions, which is beneficial for long-term treatment. Therefore, the RD regimen can be considered as the first-line treatment option for POEMS syndrome patients, and for young patients who are tolerant, it is recommended to undergo RD regimen-induced treatment followed by high-dose melphalan treatment and ASCT. The RD regimen can be considered as the first-line treatment option for POEMS syndrome patients, and for young patients who are tolerant, it is recommended to undergo RD regimen-induced treatment followed by high-dose melphalan treatment and ASCT treatment.