PF745 HIGH‐DOSE THERAPY AND AUTOLOGOUS TRANSPLANT FOR POEMS SYNDROME: EFFECTIVE, BUT HOW TO OPTIMISE?
Authors: O. Tomkins, S. Keddie, A. Cerner, J. Horder, F. Newrick, C. Yeomans, D. Foldes, M. Lunn, S. D'Sa
Journal: HemaSphere (2019)

Background: POEMS syndrome is a paraneoplastic phenomenon whose pathogenesis is not fully understood, but an underlying plasmaproliferative process appears to promote cytokine release, including vascular endothelial growth factor (VEGF) which induces capillary leakage and tissue damage. High dose melphalan‐conditioned autologous stem cell transplantation (ASCT) is an effective therapy for patients with adequate performance status who have non‐localised disease, but some patients relapse. Aims: To study the effectiveness of ASCT in POEMS syndrome, factors influencing the natural history and management of relapse. Methods: We reviewed 42 patients who underwent ASCT from 1998 to 2018. Patient characteristics, previous lines of treatment, harvesting regimens, engraftment data, episodes of engraftment syndrome (ES) and transplant‐related morbidity were recorded. Disease status at ASCT was used as the baseline. Response assessment was carried out at 3, 6 and 12 months and a tailored frequency thereafter. Time to maximal VEGF, haematological, radiological, clinical responses and the nature and management of progression events were recorded. Results: Median age at diagnosis/ASCT was 49.5/52 years; median time from diagnosis to ASCT 5.5 months. POEMS features were varied; 100% had neuropathy and raised VEGF, 80% had multifocal bone lesions, 50–70% had fluid overload, skin changes, endocrinopathy, organomegaly and other features at lower incidence; 73.8% had a serum M protein, 80.1% lambda‐restricted; 64% had up to 10% BM involvement. Overall survival (OS) was 92.9% (mean follow up 62.6 months, range 4–226 months). One‐year OS was 95.4% and progression‐free survival (PFS) was 81.6%; 5‐year OS 89.5% and PFS 76.9%. Three patients died without POEMS progression (1 peri‐transplant, I unknown cause, 1 MDS). Three patients (16.7%) had ES. Haem CR or VGPR was achieved by 50%. Average VEGF levels improved from 4,959pg/mL to 489.5pg/mL at 6 months and 330pg/mL at 1 year ( p &lt; 0.001). Significant neurological improvement was seen in all but 2 patients (median pre‐ to post‐transplant Overall Neuropathy Limitation Scale score from 6 to 2 ( p &lt; 0.01)). Median time to first improvement was 4 months. Nerve conduction studies demonstrated continued improvement even 3 years after ASCT. Six patients (14.3%) have relapsed to date. No patient who achieved haem CR has relapsed, compared to those with &lt;CR (31.6% relapse rate (p = 0.027)). Treatment for relapse was implemented for symptomatic reasons; fatigue and raised VEGF were common to all, other features were varied and unique to each patient. Of the 4 patients treated with lenalidomide and dexamethasone, 2 have stopped (unacceptable toxicity; no clinical benefit despite VEGF response). Summary/Conclusion: This analysis confirms that ASCT is an effective treatment for POEMS and attainment of haem CR after ASCT is associated with a lower relapse rate. No patients who achieved clearance of bone marrow plasma cell clones and paraproteinaemia in our cohort have relapsed, compared to almost a third of those with a persistent clonal burden. How to manage relapse remains contentious; identification of clinically significant relapse remains challenging; a raised VEGF alone does not tell the whole story. Appropriate management of relapse, including optimum treatment agents, depth and duration remains unclear. Clinical trials of novel agents are urgently needed. More informative, readily applicable clinical and laboratory tools are needed to guide therapeutic decision‐making, including biomarkers that have prognostic significance. image