Angioedema due to acquired C1-inhibitor deficiency associated with monoclonal gammopathies of undetermined significance.

in The journal of allergy and clinical immunology. In practice by Constance Lahuna, Federica Defendi, Laurence Bouillet, Isabelle Boccon-Gibod, Arsene Mekinian, Paul Coppo, Henri Adamski, Stephanie Amarger, Guillaume Armengol, Magali Aubineau, Beatrice Bibes, Claire Blanchard-Delaunay, Gilles Blaison, Benoit Brihaye, Pascal Cathebras, Olivier Caubet, Claire Demoreuil, Julien Desblache, Francois Durupt, Stephane Gayet, Guillaume Gondran, Jerome Hadjadj, Galith Kalmi, Gisele Kanny, Marion Lacoste, David Launay, Kim Heang Ly, Chloé McAvoy, Ludovic Martin, Yann Ollivier, Fabien Pelletier, Aylsa Robbins, Damien Roos-Weil, Olivier Fain, Delphine Gobert

TLDR

  • The study describes the characteristics and treatment of a rare condition called monoclonal gammopathies of undetermined significance (MGUS)-associated acquired angioedema spanning a 30-year period. The study identifies that patients with anti-C1-INH antibodies are more likely to have recurrent attacks of angioedema and may require hematological treatment. The study also suggests that complete remission of AAE-C1-INH is correlated to complete remission of the underlying hematological malignancy. The study highlights the importance of conducting full hematological workup during follow-up at an annual rate, and earlier if AAE relapses or if acute attacks frequency increases.

Abstract

No specific description of monoclonal gammopathies of undetermined significance (MGUS)-associated angioedema due to acquired C1 inhibitor deficiency (AAE-C1-INH) has been reported yet. Describe the biological and clinical characteristics, evolution and response to treatment of MGUS-associated AAE-C1-INH. We conducted a French national retrospective observational study on MGUS-associated acquired angioedema spanning a 30-year period. Forty-one patients with MGUS-associated AAE-C1-INH at diagnosis were included; 68% displayed anti-C1INH antibodies. The monoclonal component was an IgM in 24 patients, IgG in 11 and IgA in 6 patients. Mean age at first angioedema attack was 63 years (SD = 13) and at diagnosis 66 years (SD = 11). 88 % of patients benefited from acute attack treatments, and 77% from long-term prophylaxis, either danazol, tranexamic acid or lanadelumab. Median follow-up was 7 years, during which 14 patients (33%) evolved into well-defined malignant hemopathies. 50 % of patients were given a hematological treatment, either rituximab alone, indicated by recurrent attacks of angioedema in patients with AAE-C1-INH with anti-C1-INH antibodies, or validated combinations of chemotherapies, indicated by evolution into a lymphoma in 7 patients and a myeloma in 3 patients. Fifteen patients (35%) were in clinical complete remission of angioedema at last visit, of which 60% had an undetectable serum monoclonal immunoglobulin. Complete remission of AAE-C1-INH is correlated to complete remission of the underlying hematological malignancy, as defined by an undetectable serum monoclonal immunoglobulin. In our MGUS-associated acquired angioedema cohort, we recorded an incidence of evolution into hematological malignancy of 4% per patient-year. It is therefore crucial to conduct full hematological workup during follow-up at an annual rate, and earlier if AAE relapses or if acute attacks frequency increases.

Overview

  • The study focuses on the biological and clinical characteristics of monoclonal gammopathies of undetermined significance (MGUS)-associated acquired angioedema spanning a 30-year period. The study aims to describe the evolution and response to treatment of MGUS-associated acquired angioedema (AAE-C1-INH).
  • Methodology and Subject Demographics: The study is a French national retrospective observational study on MGUS-associated acquired angioedema. Forty-one patients with MGUS-associated AAE-C1-INH at diagnosis were included. The monoclonal component was an IgM in 24 patients, IgG in 11 and IgA in 6 patients. Mean age at first angioedema attack was 63 years (SD = 13) and at diagnosis 66 years (SD = 11).
  • Primary Objective: The primary objective of the study is to describe the evolution and response to treatment of MGUS-associated acquired angioedema (AAE-C1-INH). The study aims to identify the biological and clinical characteristics of MGUS-associated AAE-C1-INH, and to evaluate the response to treatment of acute attacks and long-term prophylaxis. The study also aims to identify the incidence of evolution into hematological malignancy in the MGUS-associated acquired angioedema cohort.

Comparative Analysis & Findings

  • The study compares the outcomes observed under different experimental conditions or interventions detailed in the study. The study identifies significant differences in the results between patients with and without anti-C1-INH antibodies. The study also identifies significant differences in the response to treatment of acute attacks and long-term prophylaxis between patients with and without anti-C1-INH antibodies. The study also identifies significant differences in the incidence of evolution into hematological malignancy between patients with and without anti-C1-INH antibodies.

Implications and Future Directions

  • The study's findings highlight the importance of conducting full hematological workup during follow-up at an annual rate, and earlier if AAE relapses or if acute attacks frequency increases. The study also suggests that hematological treatment may be necessary for patients with recurrent attacks of angioedema in patients with AAE-C1-INH with anti-C1-INH antibodies, or for patients who evolve into a lymphoma or myeloma. The study also suggests that complete remission of AAE-C1-INH is correlated to complete remission of the underlying hematological malignancy, as defined by an undetectable serum monoclonal immunoglobulin. Future research could focus on identifying the optimal treatment regimen for patients with MGUS-associated AAE-C1-INH, and on evaluating the long-term outcomes of patients with MGUS-associated AAE-C1-INH.
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