Nationwide real-world outcomes of POEMS syndrome: Long-term impact of ASCT, maintenance therapy, and relapse strategies in Japan Free

Introduction POEMS syndrome is a rare plasma cell disorder classified as a myeloma-related disease. It presents complex multisystem involvement including polyneuropathy and lacks standardized treatment guidelines. Although the efficacy of autologous stem cell transplantation (ASCT) has been demonstrated, the optimal strategies for maintenance therapy and relapse management remain unclear. Due to its clinical and biological overlap with multiple myeloma, treatment approaches used in myeloma have been considered for POEMS syndrome, but their applicability, especially in relapsed or refractory settings, is uncertain.

A nationwide survey in Japan conducted in 2014 showed the benefits of ASCT for POEMS syndrome. However, approximately 40% of patients relapsed or progressed within five years. The use of novel agents has become standard in multiple myeloma, yet their efficacy in POEMS syndrome remains to be clarified. This study aimed to evaluate real-world long-term outcomes after ASCT, explore the role of maintenance therapy, and analyze treatment strategies for relapsed/refractory cases in Japan to support future guideline development.

Methods This project was conducted as a nationwide secondary research study approved by the Japanese Society for Transplantation and Cellular Therapy (JSTCT), using the Transplant Registry Unified Management Program (TRUMP®) database managed by JSTCT and the Japanese Data Center for Hematopoietic Cell Transplantation (JDCHCT). Patients who underwent ASCT for POEMS syndrome from January 2010 to December 2019 were included. A follow-up survey was conducted to obtain detailed clinical data. The institutional review board (IRB) reviewed and approved the study protocol.

Results Data from 107 patients and 112 ASCT procedures at 33 centers were analyzed. The median age was 52 years (range: 16–72), with 59% male. The most common immunoglobulin subtype was IgA lambda (49.5%). The median serum VEGF at diagnosis was 4460 pg/mL, and median time to ASCT was 6.4 months. Pre-transplant conditioning included high-dose melphalan (MEL200) in 85.9% of patients. Before ASCT, 85% received prior therapy with immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs), steroids, or other agents.

With a median follow-up of 79.2 months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 92.0% and 74.0%, respectively. Maintenance therapy was planned for 13 patients (12.1%), starting at a median of 131 days post-ASCT (range: 39–406) and continuing up to 3429 days. Regimens included IMiDs (n=8), PI-based regimens (n=3), melphalan/dexamethasone (n=3), ixazomib (n=1), and radiation therapy (RT, n=1). The 5-year PFS in the maintenance group was 81.1%.

Relapses occurred in 31 patients (29.0%) at a median of 927 days post-ASCT. All but one received further treatment, including RT (n=1), IMiD-based regimens (n=29), PI-based (n=10), and daratumumab-based regimens (n=10). Three patients underwent a second or third ASCT. Among relapsed/refractory patients, the 3-year OS was 84.0% (median follow-up: 31.3 months). Secondary malignancies developed in 9 patients (8.4%). Fourteen patients (13.1%) died: disease progression (n=3), infections (n=7), and other causes (n=4).

Conclusion This nationwide study provides real-world data on ASCT outcomes, maintenance therapy, and relapse management in Japanese patients with POEMS syndrome. Long-term survival was favorable, but relapses occurred in nearly 30% of patients. Maintenance therapy, although limited in use, was associated with improved PFS, particularly with IMiD-based regimens. Relapse treatments were diverse and increasingly included novel agents like daratumumab, reflecting a shift toward individualized and immunotherapy-based approaches. The use of second or third ASCT in selected cases also suggests the continued relevance of high-dose chemotherapy. However, secondary malignancies and infections remain significant concerns and call for careful surveillance and supportive care. Future research should focus on global analyses and prospective studies to validate optimal post-transplant strategies and improve long-term outcomes in POEMS syndrome.