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

Treatment of POEMS Syndrome

For POEMS syndrome with localized disease (solitary or limited sclerotic bone lesions), radiation therapy is the definitive first-line treatment and achieves long-lasting responses in the majority of patients; for disseminated disease, systemic chemotherapy is required, with melphalan-dexamethasone or lenalidomide-dexamethasone as preferred regimens, followed by autologous stem cell transplantation (ASCT) in eligible patients. 1

Treatment Algorithm Based on Disease Extent

Localized Disease (No Bone Marrow Involvement)

• Radiation therapy is the treatment of choice for patients with solitary or limited sclerotic bone lesions without bone marrow involvement 1
• Radiation achieves 97% 4-year overall survival and 52% 4-year failure-free survival in retrospective analyses 1
• Improvement occurs in 50-70% of patients treated with radiation alone 1
• Large bone lesions may require adjuvant radiation, typically administered 6 months after chemotherapy if systemic therapy was needed 1

Disseminated Disease (Bone Marrow Involvement or Multiple Lesions)

First-line systemic therapy options include:

• Melphalan-dexamethasone (MDex): Achieves 81% hematologic response and 100% improvement in neuropathy in prospective trials 1
• Lenalidomide-dexamethasone: Preferred option for transplant-ineligible patients, with majority of patients responding 1, 2
• Cyclophosphamide-dexamethasone: Results in 50% clinical improvement 1
• Bortezomib monotherapy: Achieves complete remission/very good partial remission in 69% of patients, making it the most effective single-agent therapy 3

Critical caveat: Avoid bortezomib-based regimens as first-line therapy due to high risk of treatment-related neuropathy worsening pre-existing polyneuropathy 1

Autologous Stem Cell Transplantation

• ASCT should be offered to eligible patients with disseminated disease after induction chemotherapy 1
• ASCT achieves 100% clinical improvement in transplant-eligible patients 1
• Patients proceeding to planned ASCT demonstrate statistically superior progression-free survival and overall survival compared to non-ASCT patients (P=0.003) 3
• Approximately 30% of patients proceed to planned ASCT as part of front-line treatment 3

Expected Timeline of Response

• Neurologic improvement significantly lags behind hematologic response 1
• Maximum neurologic response is expected after 2-3 years of successful therapy 1
• Optimal response on FDG-PET may lag by 6-12 months after treatment 1
• Patients should be counseled about this delayed response to avoid premature treatment changes 1

Agents to Avoid

Do not use the following as first-line therapy:

• Thalidomide-based regimens: High neurotoxicity risk that can worsen pre-existing neuropathy 1
• Bortezomib-based combinations: Not recommended as first-line due to induced neuropathy risk, despite high response rates 1, 4
• Bevacizumab: Will reduce VEGF levels but associated with several death reports 1

Relapsed/Refractory Disease

• Limited data exist for relapsed disease management 2
• Consider proteasome inhibitors, immunomodulatory agents, or alternative chemotherapy regimens 2
• International collaboration is needed to define optimal relapse treatment strategies 2

Monitoring and Supportive Care

• Serum VEGF levels should be monitored as a marker of disease activity and treatment response 1, 5
• Endocrinopathy management: Address thyroid, adrenal, and gonadal dysfunction 5
• Thrombotic risk management: Monitor for thrombocytosis and consider prophylaxis 1, 5
• Neuropathic pain control: Use gabapentin, duloxetine, or tricyclic antidepressants 6
• Pulmonary function and cardiac assessment: Regular monitoring with pulmonary function tests and echocardiography 1, 5

Common Pitfalls

• Misdiagnosis as CIDP or MGUS-associated neuropathy delays appropriate treatment; clues include thrombocytosis and sclerotic bone lesions on radiographs 7
• Using CIDP treatments (IVIG, plasmapheresis) are ineffective in POEMS syndrome 7
• Premature discontinuation of therapy due to slow neurologic response; continue treatment and monitor for 2-3 years 1
• Selecting neurotoxic agents in patients with severe baseline neuropathy worsens outcomes 1