What is the treatment approach for POEM (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy) syndrome?

Treatment of POEMS Syndrome

For localized POEMS syndrome with solitary or limited sclerotic bone lesions, radiation therapy is the definitive first-line treatment; for disseminated disease with diffuse bone lesions or bone marrow involvement, systemic chemotherapy (melphalan-dexamethasone or lenalidomide-dexamethasone) followed by autologous stem cell transplantation in eligible patients is the recommended approach. 1, 2

Treatment Algorithm Based on Disease Extent

Localized Disease

• Radiation therapy alone is curative for patients with solitary or limited sclerotic bone lesions without bone marrow involvement, achieving 97% 4-year overall survival and 52% 4-year failure-free survival 1, 2
• Clinical improvement occurs in 50-70% of patients treated with radiation alone 1, 3
• Do not use radiation alone for disseminated disease—it is not curative and systemic therapy is mandatory 3

Disseminated Disease

• Melphalan-dexamethasone is a preferred first-line regimen, achieving 81% hematologic response and 100% improvement in neuropathy in prospective trials 1, 2
• Lenalidomide-dexamethasone is preferred in patients with pre-existing neuropathy due to lower neurotoxicity risk compared to other agents 2, 3
• Autologous stem cell transplantation (ASCT) should be offered to eligible patients after induction chemotherapy, achieving 100% clinical improvement in transplant-eligible patients 1, 2, 3
• ASCT as part of front-line treatment results in statistically superior progression-free and overall survival compared to non-ASCT treated patients 4

Critical Agents to Avoid

• Thalidomide-based regimens should be avoided due to high neurotoxicity risk that can worsen pre-existing neuropathy 1, 2
• Bortezomib-based combinations are not recommended as first-line therapy despite high response rates (69% CR/VGPR with bortezomib monotherapy), due to induced neuropathy risk 1, 2, 3, 5, 4
• The FDA label for bortezomib specifically warns that patients with pre-existing severe neuropathy should be treated only after careful risk-benefit assessment 5

Expected Timeline and Monitoring

Response Kinetics

• Neurologic improvement significantly lags behind hematologic response—maximum neurologic response is expected after 2-3 years of successful therapy 1, 2, 3
• Do not discontinue treatment prematurely if immediate neurologic improvement is not apparent; continue therapy as the lag time is expected 3
• Optimal response on FDG-PET may lag by 6-12 months after treatment 1, 2

Disease Monitoring

• Serum VEGF levels should be monitored as a marker of disease activity and treatment response 1, 2, 3
• Complete blood counts should be monitored regularly throughout treatment, particularly for thrombocytopenia and neutropenia 5

Supportive Care Management

• Endocrinopathy management should address thyroid, adrenal, and gonadal dysfunction 1, 2
• Thrombotic risk management should monitor for thrombocytosis and consider prophylaxis 1, 2
• Pulmonary and cardiac assessment should include regular monitoring with pulmonary function tests and echocardiography, as 85.2% of patients show decreased diffuse capacity and 35.5% have pulmonary hypertension 1, 2, 6

Key Clinical Pitfalls

• POEMS syndrome is frequently misdiagnosed as chronic inflammatory demyelinating polyneuropathy (CIDP), leading to delayed therapy and progressive worsening of symptoms 7, 8
• Therapies effective for CIDP (intravenous immunoglobulin and plasmapheresis) are not effective in POEMS syndrome 8
• Early diagnostic clues include thrombocytosis and sclerotic bone lesions on plain skeletal radiographs 8
• Patients who otherwise satisfy criteria for myeloma but are symptomatic due to POEMS syndrome should be managed differently, taking into consideration the manifestations of the associated condition 2