LAHUNA C, DEFENDI F, BOUILLET L, BOCCON-GIBOD I, MEKINIAN A, COPPO P, ADAMSKI H, AMARGER S, ARMENGOL G, AUBINEAU M, BIBES B, BLANCHARD-DELAUNAY C, BLAISON G, BRIHAYE B, CATHEBRAS P, CAUBET O, DEMOREUIL C, DESBLACHE J, DURUPT F, GAYET S, GONDRAN G, HADJADJ J, KALMI G, KANNY G, LACOSTE M, LAUNAY D, LY KH, MCAVOY C, MARTIN L, OLLIVIER Y, PELLETIER F, ROBBINS A, ROOS-WEIL D, FAIN O, GOBERT D

J Allergy Clin Immunol Pract [Internet]. [cité 8 oct 2024]

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Background

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.
Objective

To describe the biological and clinical characteristics, evolution, and response to treatment of MGUS-associated AAE-C1-INH.
Materials and Methods

We conducted a French national retrospective observational study on MGUS-associated acquired angioedema spanning a 30-year period.
Results

Forty-one patients with MGUS-associated AAE-C1-INH at diagnosis were included; 68% displayed anti-C1-INH antibodies. The monoclonal component was an IgM in 24 patients, IgG in 11, and IgA in 6 patients. The mean age at first angioedema attack was 63 years (standard deviation [SD] = 13 years) and at diagnosis 66 years (SD = 11 years). A total of 88% 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. Fifty percent 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 whom 60% had an undetectable serum monoclonal immunoglobulin.
Conclusions

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 attack frequency increases.