What is the best first-line treatment for POEMS syndrome: autologous transplantation, melphalan and dexamethasone, or lenalidomide and dexamethasone?

POEMS syndrome is a rare plasma cell dyscrasia. This study compared the responses to and survival of 347 POEMS syndrome patients given three first-line treatment regimens: autologous stem cell transplantation (ASCT, N = 165) and melphalan + dexamethasone (MDex, N = 79), or lenalidomide + dexamethasone (LDex, N = 103). After a median 45-month follow-up, overall hematologic complete remission (CR(H)) was 46.4%, vascular endothelial growth factor complete remission (CR(V)) was 55.1%, and neurological remission (R(N)) was 93.8%. CR(H) was better with ASCT (49.7%) than with MDex (37.7%, p = 0.001). CR(V) was better with ASCT (66.2%) than with MDex (38.5%, p = 0.001) or LDex (47.7%, p = 0.008). Differences in R(N) achieved by three regimens (91.5% vs. 100% vs. 93.8%, p = 0.234) were not significant. Overall 3-year progression-free survival (PFS) was 80.5% and overall 3-year overall survival (OS) was 90.8%. PFS was 87.6% with ASCT and 64.9% with LDex (p = 0.003). OS in the three regimens did not differ (p = 0.079). In medium-high risk patients, ASCT had better CR(H) and CR(V) than MDex, and better PFS than LDex. Therefore, although all three treatments had reasonable responses and survivals, patients with higher risk may benefit more from ASCT treatment.