Lenalidomide therapy in a patient with POEMS syndrome

To the editor:

The immune modulatory drugs (IMiDs) are powerful drugs against malignant plasma cells.^1,2  They also reduce the production of proinflammatory and proangiogenic cytokines. The POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes) syndrome is a paraneoplastic syndrome that is driven by such cytokines,³  most notably vascular endothelial growth factor (VEGF).⁴  There are anecdotal reports of benefit of thalidomide for patients with POEMS.⁵  Enthusiasm for its use in a condition in which the dominant complaint is sensorimotor peripheral neuropathy is tempered by the high incidence of thalidomide-induced peripheral neuropathy with long-term use.⁶ 

A 40-year-old African-American man presented to the Mayo Clinic with a 4-year course of progressive peripheral neuropathy, weight-loss, fatigue, anasarca, hypertrichosis, hyperpigmentation, gynecomastia, and erectile dysfunction. One year into his symptoms, he was diagnosed with chronic inflammatory demyelinating neuropathy (CIDP). For this diagnosis, he was treated with corticosteroids, plasmapheresis, and finally azathioprine without significant benefit. He continued to deteriorate, and a diagnosis of POEMS was made based on the following findings: peripheral neuropathy, organomegaly (lymphadenopathy and mild splenomegaly), endocrinopathy (primary gonadal insufficiency, elevated prolactin, and gynecomastia), monoclonal protein (IgG lambda), skin changes (hyperpigmentation, hypertrichosis), anasarca, diffuse sclerotic bone lesions, abnormal pulmonary function tests, plasma IL-6 of 140 pg/mL, and plasma VEGF 948 pg/mL. Bone marrow had 5% monoclonal lambda plasma cells. On metaphase cytogenetics, t(9;17)(q22;q25) was seen in 2 of 32 cells.

Given his poor performance status, early high-dose chemotherapy with peripheral blood stem cell transplantation was not an option.⁷  He was started on lenalidomide 15 mg per day for 21 days of a 28-day cycle with once-weekly dexamethasone (40 mg). The dose of lenalidomide was gradually increased to the standard 25-mg dose. In total, he received 9 cycles of treatment over a course of 9 months.

By his third cycle of therapy, he was able to perform more ADLs and use a walker with more ease. After 4 cycles, he was depending on his walker rather than wheelchair, and by 6 months, he had only trace ankle edema. By 10 months (6 weeks after his last cycle), his functional status, VEGF and IL-6 levels, skin changes, and anasarca had improved substantially. Modest improvements were also seen in his pulmonary function tests, polyclonal hypergammaglobulinemia, and testosterone levels. The most salient findings are shown in Table 1. The treatment plan is to consolidate his response with high-dose peripheral stem cell transplantation.

Like the observation made by Badros et al using anti-VEGF antibodies to treat patients with POEMS,⁸  the use of lenalidomide supports the principle that POEMS is a cytokine-mediated syndrome. The 3 cases of bevacizumab use in patients with POEMS would suggest that anti-VEGF antibodies alone are likely not sufficient⁹  since anti-VEGF antibodies do little against the clonal plasma cells. The 2 responses seen with bevacizumab were in patients receiving concomitant alkylator.^8,9  Lenalidomide has the advantage of being both immune modulatory and cytotoxic to malignant plasma cells. This observation opens a new treatment option for patients with POEMS syndrome.