IgA vasculitis with underlying monoclonal IgA gammopathy: innovative therapeutic approach targeting plasma cells. A case series

Clin Rheumatol. 2022 Oct;41(10):3119-3123. doi: 10.1007/s10067-022-06181-4. Epub 2022 Jun 17.

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.

Keywords: Gammopathy; Henoch-Schönlein purpura; IgA vasculitis; Immunoglobulin A; Monoclonal plasma cells; Multiple myeloma.

MeSH terms

  • Bortezomib / therapeutic use
  • Cyclophosphamide / therapeutic use
  • Dexamethasone / therapeutic use
  • Humans
  • IgA Vasculitis*
  • Immunoglobulin A
  • Lenalidomide
  • Melphalan
  • Monoclonal Gammopathy of Undetermined Significance* / complications
  • Monoclonal Gammopathy of Undetermined Significance* / drug therapy
  • Paraproteinemias* / complications
  • Paraproteinemias* / drug therapy
  • Peripheral Nervous System Diseases* / drug therapy
  • Plasma Cells
  • Prednisone
  • Retrospective Studies
  • Rituximab / therapeutic use

Substances

  • Immunoglobulin A
  • Rituximab
  • Bortezomib
  • Dexamethasone
  • Cyclophosphamide
  • Lenalidomide
  • Melphalan
  • Prednisone