Pilot Study with Lenalidomide in Patients with POEMS Syndrome
Authors: Nozza Andrea , Terenghi Fabrizia , Mazza Rita , Orazio Eduardo Nobile , Adami Fausto , Merlini Giampaolo , Briani Chiara , Palladini Giovanni , Grasso Mariella , Gandolfi Sara , Carlo-Stella Carmelo , Santoro Armando 
Published: October 2019

Abstract
Abstract 4612

Introduction:
POEMS syndrome is a rare multisystemic disease. Vascular endothelial growth factor (VEGF) correlates with the activity of the disease and it could account for clinical manifestations. Actually no controlled trials are available and there is no clear evidence for a standard therapeutic approach. Lenalidomide has anti-angiogenic activity through inhibition of VEGF and TNF alpha The aim of this study is to evaluate efficacy and safety of Lenalidomide in POEMS syndrome.

Patients & method:
From 10/09, we started a pilot study with Lenalidomide plus dexamethasone (RD) in pretreated or newly diagnosed POEMS patients not eligible for transplant procedure.
Lenalidomide 25 mg/day was given for 21 days in association with weekly dexamethasone 40 mg until toxicity or progression occurred. After 6 cycles, pts were evaluated for response.
Utonow 10pts have been enrolled, 9 men and 1 woman; median age was 51 years (range 45–76). All pts were pretreated and 2 pts had previously received high-dose melphalan with peripheral blood stem cell transplant. Monoclonal component (MC) was detected in all pts: IgAl in 3 pts, IgG l in 6 pts, l light chain in 1; all pts had sensory/motor peripheral neuropathy. Sclerotic bone lesions were detected in 5 pts, endocrinopathies in 8 pts, skin changes in 8 pts, peripheral edema in 8 pts, organomegaly in 7 pts, lymphoadenophaty in 3 pts, papilledema in 7 pts, thrombocytosis in 3 pts. VEGF serum level was elevated in all patient with a median value of 3544 pg/ml (range 1430–9788).

Results:
Seven pts are still on treatment with a median of 10 RD cycles (range 5–18). Six pts are evaluable for response after 6 cycles. A clinical response, with improvement of all disease manifestations, was observed in all pts. Neurological improvement was observed after 3 RD cycles, and was confirmed by nerve conduction studies after 6 cycles. One patient with tetraparesis is currently able to walk and his upper limb strength is normal with improved sensory neuropathy. MC disappeared in 2 patients. VEGF levels decreased in all pts: from a median of 3544 pg/ml (range 1430–9788) before treatment to 1539 pg/ml (467-3579) after 6 cycles. Three pts discontinued treatment: 1 withdrew consensus, 1 dropped out after 4 cycles for progression and 1 died for pulmonary infection on cycle 1. Dexamethasone dose adjustment was necessary in 5 pts and lenalidomide in 2 pts, (1 extraematological toxicity and 11 thrombocytopenia).

Conclusions:
This preliminary analysis,although in a limited series, highlights efficacy and safety of Lenalidomide in POEMS. Noteworthy the neurological improvement has been rapid and continuous, also in heavily pre-treated pts. At this time no patients experienced disease progression. A clear relationship between response and VEGF level was confirmed. The study accrual is ongoing.

Disclosures:
Off Label Use: Bortezomib and Thalidomide as induction therapy prior to and consolidation therapy after double autologous stem-cell transplantation in newly diagnosed multiple myeloma.