Clinical features, dominant paraprotein, and treatment of multi-organ and hematologic MGCS syndromes
| MGCS subtype . | Clinical features . | Dominant paraprotein . | Treatment . |
|---|---|---|---|
| Multi-organ syndromes | |||
| - Cryoglobulinemia | Livedo reticularis, distal ischemia, neuropathy, glomerulonephritis, hyperviscosity, arthralgia | IgM and IgG | • Treatment of underlying cause • Clone-directed therapy • Steroids • Rituximab +/- steroids • Plasmapheresis |
| - POEMS | Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, sclerotic bone lesions and skin changes, anasarca, thrombocytosis/erythrocytosis | Lambda (esp. IgA lambda) | • Radiation if focal 1-2 bone lesions present and bone marrow is negative • Plasma-cell-directed therapy (ASCT; lenalidomide/dex; anti-CD38 antibody) |
| - Schnitzler syndrome | Urticaria, sclerotic bone lesions, constitutional symptoms | IgM kappa | • IL-1 blockade |
| - TEMPI syndrome | Telangiectasia, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collection, intrapulmonary shunting | No identified immunoglobulin or light chain specificity | • Plasma-cell-directed therapy |
| Hematologic MGCS | |||
| - CAD | Red cell agglutination, positive Coombs for C3, high cold agglutinin titer, thermal amplitude ≥30° C | IgM kappa | • Rituximab • Bendamustine-rituximab • BTK inhibitor • Venetoclax • Sutimlimab |
| - MGTS | Unexplained, recurrent thrombosis | IgG | • Anticoagulation • Plasma-cell-directed therapy • Plasma exchange |
| MGCS subtype . | Clinical features . | Dominant paraprotein . | Treatment . |
|---|---|---|---|
| Multi-organ syndromes | |||
| - Cryoglobulinemia | Livedo reticularis, distal ischemia, neuropathy, glomerulonephritis, hyperviscosity, arthralgia | IgM and IgG | • Treatment of underlying cause • Clone-directed therapy • Steroids • Rituximab +/- steroids • Plasmapheresis |
| - POEMS | Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, sclerotic bone lesions and skin changes, anasarca, thrombocytosis/erythrocytosis | Lambda (esp. IgA lambda) | • Radiation if focal 1-2 bone lesions present and bone marrow is negative • Plasma-cell-directed therapy (ASCT; lenalidomide/dex; anti-CD38 antibody) |
| - Schnitzler syndrome | Urticaria, sclerotic bone lesions, constitutional symptoms | IgM kappa | • IL-1 blockade |
| - TEMPI syndrome | Telangiectasia, elevated erythropoietin and erythrocytosis, monoclonal gammopathy, perinephric fluid collection, intrapulmonary shunting | No identified immunoglobulin or light chain specificity | • Plasma-cell-directed therapy |
| Hematologic MGCS | |||
| - CAD | Red cell agglutination, positive Coombs for C3, high cold agglutinin titer, thermal amplitude ≥30° C | IgM kappa | • Rituximab • Bendamustine-rituximab • BTK inhibitor • Venetoclax • Sutimlimab |
| - MGTS | Unexplained, recurrent thrombosis | IgG | • Anticoagulation • Plasma-cell-directed therapy • Plasma exchange |
ASCT, autologous stem cell transplant; BTK, Bruton tyrosine kinase; CAD, cold agglutinin disease; IL-1, interleukin-1; MGTS, monoclonal gammopathy of thrombotic significance.