Antoine Hankard1, Saskia Ingen-Housz-Oro2, Khalil El Karoui3, Romain Paule4, Bertrand Lioger5, Benoit Brihaye6, Maxime Battistella7, Stéphanie Jobard8, Julie Magnant8, Elisabeth Diot8, Adrien Bigot8, Nicole Ferreira-Maldent8, Sophie Deriaz8, Ann-Rose Cook8, Hélène Henique8, Francois Maillot8,9, Achille Aouba1, Alexandra Audemard-Verger10,11. 1. Department of Internal Medicine, CHU de Caen, Caen, France. 2. Department of Dermatology, AP-HP, Hôpital Henri Mondor, Créteil, France. 3. Department of Nephrology, Hôpital Henri Mondor, Creteil, France. 4. Department of Internal Medicine, Hôpital Foch, Suresne, France. 5. Department of Internal Medicine, Hôpital de Blois, Blois, France. 6. Department of Internal Medicine, CH Saint Quentin, Saint Quentin, France. 7. Department of Pathology, Hôpital Saint Louis, Paris, France. 8. Department of Internal Medicine and Clinical Immunology, CHRU Tours, Tours, France. 9. University of Tours, Tours, France. 10. Department of Internal Medicine and Clinical Immunology, CHRU Tours, Tours, France. a.audemard-verger@chu-tours.fr. 11. University of Tours, Tours, France. a.audemard-verger@chu-tours.fr.
Abstract
OBJECTIVE: There is currently no evidence of the possible benefit of plasma cell-targeting therapies (PCTT) in immunoglobulin A (IgA) monoclonal gammopathy (MG) associated with IgA vasculitis (IgAV). We report the outcome of different PCTT regimens in a cohort of MG-IgAV. METHODS: We used a French network to retrospectively describe the outcome of MG-IgAV patients treated with PCTT. RESULTS: Five patients were included (mean age 65 years). All patients had severe baseline presentation including extensive necrotic purpura (n = 5), gastrointestinal involvement (n = 2), peripheral neuropathies (n = 2), and glomerulonephritis (n = 1). Two patients had IgA indolent multiple myeloma and three had IgA "MG of undetermined significance." Monotypic IgA deposition in the skin vessels wall was highlighted using an immunofluorescence assay. Cases of vasculitis in three patients (n = 3) were refractory to multiple line therapies, including cyclophosphamide (n = 3) or rituximab. Finally, PCTT including bortezomib plus cyclophosphamide and dexamethasone, bortezomib plus melphalan and prednisone, or bortezomib plus lenalidomide and dexamethasone were proposed, allowing complete remission in 4/5 patients without major adverse drug events. CONCLUSION: This study suggests that the MG-IgAV phenotype might be distinctive of usual IgAV (severe and refractory to conventional immunosuppressive regimens) and supports the benefit of PCTT. This study sheds new light on the overall biology of IgAV, strengthening the pathogenic role of the monoclonal IgA component in IgAV.
OBJECTIVE: There is currently no evidence of the possible benefit of plasma cell-targeting therapies (PCTT) in immunoglobulin A (IgA) monoclonal gammopathy (MG) associated with IgA vasculitis (IgAV). We report the outcome of different PCTT regimens in a cohort of MG-IgAV. METHODS: We used a French network to retrospectively describe the outcome of MG-IgAV patients treated with PCTT. RESULTS: Five patients were included (mean age 65 years). All patients had severe baseline presentation including extensive necrotic purpura (n = 5), gastrointestinal involvement (n = 2), peripheral neuropathies (n = 2), and glomerulonephritis (n = 1). Two patients had IgA indolent multiple myeloma and three had IgA "MG of undetermined significance." Monotypic IgA deposition in the skin vessels wall was highlighted using an immunofluorescence assay. Cases of vasculitis in three patients (n = 3) were refractory to multiple line therapies, including cyclophosphamide (n = 3) or rituximab. Finally, PCTT including bortezomib plus cyclophosphamide and dexamethasone, bortezomib plus melphalan and prednisone, or bortezomib plus lenalidomide and dexamethasone were proposed, allowing complete remission in 4/5 patients without major adverse drug events. CONCLUSION: This study suggests that the MG-IgAV phenotype might be distinctive of usual IgAV (severe and refractory to conventional immunosuppressive regimens) and supports the benefit of PCTT. This study sheds new light on the overall biology of IgAV, strengthening the pathogenic role of the monoclonal IgA component in IgAV.
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