Angioedema due to Acquired C1-Inhibitor Deficiency Associated With Monoclonal Gammopathies of Undetermined Significance Characteristics of a French National Cohort.

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.