Treateatment of Newly Diagnosed Poems Syndrome: Bortezomib or Lenalidomide? Experience From Two Countries

Background and Objectives: POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes) syndrome is a rare plasma cell disorder in which treatment selection remains largely empirical. Lenalidomide-based regimens are generally preferred in the first line due to concerns about bortezomib-induced neurotoxicity, despite limited comparative evidence. We aimed to directly compare the real-world efficacy and safety of first-line bortezomib- versus lenalidomide-based regimens. Methods: In this retrospective multicenter cohort, 26 newly diagnosed POEMS patients between 2005 and 2024 from Türkiye and Italy were included. Nine patients received bortezomib-based therapy and 17 received lenalidomide–dexamethasone. Primary endpoint was overall survival (OS); secondary endpoint was hematologic response. Results: Bortezomib-based therapy achieved significantly higher rates of deep response (≥VGPR, defined as complete response or very good partial response) compared with lenalidomide (88.9% vs 35.3%; p = 0.013). Despite higher prevalence of baseline neuropathy in the bortezomib group (77.8% vs 29.4%; p = 0.038), no treatment-emergent worsening of neuropathy was observed. Model-based 5-year overall survival was 86.6% with bortezomib and 80.7% with lenalidomide (time ratio [TR] 0.61, 95% CrI 0.04–6.78), demonstrating no evidence of a survival difference between the two strategies, with similar autologous transplantation rates and toxicity profiles. Conclusion: In this multicenter real-world cohort, bortezomib-based first-line therapy was associated with markedly deeper hematologic responses without excess neurotoxicity or survival disadvantage. These findings suggest that bortezomib-based therapy may represent an effective upfront option in selected patients and support re-evaluation of first-line strategies in prospective studies.