Bevacizumab Therapy for POEMS Syndrome.

41 yr old male presented with pain and weakness of upper and lower limbs. He was bed bound with ECOG score 4. Investigations confirmed the diagnosis of POEMS (polyneuropathy, organomegaly, endocrinopathy, M protein, skin changes) syndrome. He had typical features including glomerular hemangiomas on the skin, mild hepatosplenomegaly, sensorimotor polyneuropathy, IgG lambda paraprotein 3.3g/l, elevated FSH, LH and TSH. A course of cyclophosphamide and dexamethasone was given with no clinical response. He was also given a trial of plasma exchange and parenteral Immunoglobulins. Symptoms plateaued and he was followed up with rehabilitation support. He re-presented 18 months later with widespread low-grade lymphadenopathy, stable paraprotein, ascites, poor appetite and weight loss. Lymph node biopsy showed Castleman’s disease like changes along with osteosclerotic lesions in pelvis and raised CSF protein of 3.13g/l with rest of CSF analysis being normal. Bone marrow trephine showed paratrabecular deposits of lambda light chain restricted CD38 positive plasma cells. Ascitic fluid was sterile consistent with a transudate. Vascular endothelial growth factor (VEGF) level prior to treatment was elevated at 4587 pg/ml (Normal: 72–704 pg/ml). Large volume abdominal paracentesis ranging between 2–3 litres of clear fluid was performed weekly. In view of the raised VEGF, 4 doses of Bevacizumab (anti-VEGF) 2.5mg/kg were administered as an intravenous infusion over one hour fortnightly. VEGF level normalised after first dose of bevacizumab (131.2 pg/ml) and remained normal prior to the fourth dose (136.5 pg/ml). There were no infusional reactions or haematologic adverse effects. Frequency of paracentesis decreased to three weekly, his appetite and performance status improved with ECOG score 2. 3 weeks after the fourth dose he was readmitted with tense ascites, pleural effusion, diarrhoea, pyrexia and severe abdominal pain. Meropenem resistant pseudomonas was grown from ascitic fluid. After therapeutic paracentesis and antibiotics a Leveen shunt from abdomen to right internal jugular vein was performed to prevent reaccumulation. Despite shunting, he reaccumulated fluid in the third space and developed respiratory and pre renal failure and succumbed to it. At post mortem there were non-specific changes in the lungs and heart with no evidence of pulmonary embolism or bowel perforation and Leveen shunt remained patent. Bevacizumab promptly reduced VEGF levels with significant reduction in pleural and peripheral effusion with subjective improvement in neurological status. Bevacizumab appears to induce clinical response in a proportion of patients with POEMS syndrome. We suggest that a Phase I study should be considered to identify dose, duration of therapy and safety of Bevacizumab.