POEMS Syndrome Objective Clinical Response of Polyneuropathy to Lenolidomide.

syndrome is characterized by chronic progressive polyneuropathy (P), organomegaly (O), endocrinopathy (E), serum monoclonal protein (M), and skin changes (S). The bone lesions are typically sclerotic and may be minor in number or aymptomatic. Autologous peripheral blood stem cell transplant (APBSCT) has been reported to reverse major clinical manifestations of this disease. The peripheral neuropathy is often motor and sensory, painful in many cases, and asymmetric in distribution, and is often the major disease manifestation that affects patient performance status, and requires treatment. We report a patient case of POEMS where polyneuropathy was debilitating, confirmed by nerve conduction studies (NCS) with rapid clinical improvement on lenolidomide treatment and objective reversal of findings on NCS. The patient is a 54 year old man who developed slight leg weakness while exercising, and progressive severe lower back pain radiating down his right leg more than left. Plain X-ray showed an abnormality of the T4 and L3 vertebrae, and MRI showed a hypodense abnormality of the T3 vertebra and sclerotic area at the L2-3 vertebra. CT guided biopsy of these lesions showed plasma cells staining positive for CD 138 ; karyotype on the biopsy lesion was negative. The skeletal X-ray series was negative other than T4 and L3. Bone marrow biopsy showed no increase in plasma cells. Body CT showed multiple sclerotic lesions at the bodies of the pubis bones, left ischial tuberosity, femoral heads (left more than right), right sacrum, L3 and T12 vertebral body. PET scan showed uptake in these areas, SUV 3-4.6 The next MRI suggested 2 new sacral lesions and a new T7 lesion.

At presentation, he had very remarkable motor and sensory changes in the right leg greater than the left with sensory neuropathy, proprioception and parasthesias. He had dysesthesias, parasthesias and loss of sensation. Nerve conduction studies showed complete loss of motor potentials in the right peroneal and right posterior tibial area and sensory abnormalities in the right sural nerve. He had bilateral foot drop with poor of balance and used a rolling walker, and subjective sensory loss and numbness of the distal extremities with dysthesias and parasthesias. Motor exam of lower extremities notable for 5/5 in the proximal muscles, foot and toe flexion 4/5 bilaterally. Upper extremities and cranial nerves intact except for poor hand grip strength.

SPEP showed small monoclonal IgG lambda band of 0.3 g/dl, immunofixation (urine) showed monoclonal free lambda light chains. Serum free light chains showed a ratio reversal of Lambda 44 to kappa 28. Quantitative immunoglobulins UPEP, CBC and ESR were within normal range. Patient's bone marrow was negative for multiple myeloma and amyloidosis. Lenalidomide was started at 15 mg/day for 21 days of a 28 day cycle with once weekly dexamethasone 40mg. By the second month patient was on therapy, his performance status improved to ECOG 1, with resolution of pain within the first cycle. Repeat nerve conduction studies after 4 cycles of Len/Dex confirmed marked improvement of motor and sensory nerve potentials. Patient underwent APBSCT and had a continued clinical improvement for two years, and was able to return to full time work.

Lenalidomide is an effective treatment for POEMS syndrome, with rapid and objectively documented improvement in polyneuropathy. As POEMS may be a cytokine-mediated disorder, the immunomodulatory effects of lenolidomide may explain its benefit in these patients.

Mohrbacher:Celgene: Speakers Bureau. Off Label Use: lenolidomide.