The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease
Daratumumab is a monoclonal antibody directed against the transmembrane glycoprotein CD38 expressed on plasma cells and lymphoplasmocytes, with a proven efficacy in multiple myeloma. Here we show its clinical efficacy in a patient with cold agglutinin disease (CAD) relapsed after multiple lines of t...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2021-03-01
|
| Series: | Frontiers in Immunology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fimmu.2021.649441/full |
| _version_ | 1818329998352711680 |
|---|---|
| author | Anna Zaninoni Juri A. Giannotta Anna Gallì Rosangela Artuso Paola Bianchi Luca Malcovati Luca Malcovati Wilma Barcellini Bruno Fattizzo |
| author_facet | Anna Zaninoni Juri A. Giannotta Anna Gallì Rosangela Artuso Paola Bianchi Luca Malcovati Luca Malcovati Wilma Barcellini Bruno Fattizzo |
| author_sort | Anna Zaninoni |
| collection | DOAJ |
| description | Daratumumab is a monoclonal antibody directed against the transmembrane glycoprotein CD38 expressed on plasma cells and lymphoplasmocytes, with a proven efficacy in multiple myeloma. Here we show its clinical efficacy in a patient with cold agglutinin disease (CAD) relapsed after multiple lines of therapy. CAD is caused by cold reactive autoantibodies that induce complement mediated hemolysis and peripheral circulatory symptoms. The disease is also characterized by the presence of monoclonal IgM gammopathy and of a lymphoid bone marrow infiltration that benefits from B-cell targeting therapies (i.e., rituximab) but also from plasma cell directed therapies, such as proteasome inhibitors. In the patient described, we also show that daratumumab therapy influenced the dynamics of several immunoregulatory cytokine levels (IL-6, IL-10, IL-17, IFN-γ, TNF-α, TGF-β) indicating an immunomodulatory effect of the drug beyond plasma cell depletion. In addition, we provide a literature review on the use of daratumumab in autoimmune conditions, including multi-treated and refractory patients with autoimmune hemolytic anemia (both CAD and warm forms), Evans syndrome (association of autoimmune hemolytic anemia and immune thrombocytopenia) and non-hematologic autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis. |
| first_indexed | 2024-12-13T12:56:58Z |
| format | Article |
| id | doaj.art-7bcf3a9fff5e42d090ba02bb065b0b92 |
| institution | Directory Open Access Journal |
| issn | 1664-3224 |
| language | English |
| last_indexed | 2024-12-13T12:56:58Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Immunology |
| spelling | doaj.art-7bcf3a9fff5e42d090ba02bb065b0b922022-12-21T23:45:09ZengFrontiers Media S.A.Frontiers in Immunology1664-32242021-03-011210.3389/fimmu.2021.649441649441The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin DiseaseAnna Zaninoni0Juri A. Giannotta1Anna Gallì2Rosangela Artuso3Paola Bianchi4Luca Malcovati5Luca Malcovati6Wilma Barcellini7Bruno Fattizzo8Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, ItalyFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, ItalyDepartment of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, ItalyMedical Genetics Unit, Meyer Children's University Hospital, Florence, ItalyFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, ItalyDepartment of Hematology Oncology, Fondazione IRCCS Policlinico San Matteo, Pavia, ItalyDepartment of Molecular Medicine, University of Pavia, Pavia, ItalyFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, ItalyFondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, University of Milan, Milan, ItalyDaratumumab is a monoclonal antibody directed against the transmembrane glycoprotein CD38 expressed on plasma cells and lymphoplasmocytes, with a proven efficacy in multiple myeloma. Here we show its clinical efficacy in a patient with cold agglutinin disease (CAD) relapsed after multiple lines of therapy. CAD is caused by cold reactive autoantibodies that induce complement mediated hemolysis and peripheral circulatory symptoms. The disease is also characterized by the presence of monoclonal IgM gammopathy and of a lymphoid bone marrow infiltration that benefits from B-cell targeting therapies (i.e., rituximab) but also from plasma cell directed therapies, such as proteasome inhibitors. In the patient described, we also show that daratumumab therapy influenced the dynamics of several immunoregulatory cytokine levels (IL-6, IL-10, IL-17, IFN-γ, TNF-α, TGF-β) indicating an immunomodulatory effect of the drug beyond plasma cell depletion. In addition, we provide a literature review on the use of daratumumab in autoimmune conditions, including multi-treated and refractory patients with autoimmune hemolytic anemia (both CAD and warm forms), Evans syndrome (association of autoimmune hemolytic anemia and immune thrombocytopenia) and non-hematologic autoimmune diseases, such as systemic lupus erythematosus and rheumatoid arthritis.https://www.frontiersin.org/articles/10.3389/fimmu.2021.649441/fullcold agglutinin diseasedaratumumabcytokinesautoimmune diseasesanti-CD38 MoAb |
| spellingShingle | Anna Zaninoni Juri A. Giannotta Anna Gallì Rosangela Artuso Paola Bianchi Luca Malcovati Luca Malcovati Wilma Barcellini Bruno Fattizzo The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease Frontiers in Immunology cold agglutinin disease daratumumab cytokines autoimmune diseases anti-CD38 MoAb |
| title | The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease |
| title_full | The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease |
| title_fullStr | The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease |
| title_full_unstemmed | The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease |
| title_short | The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease |
| title_sort | immunomodulatory effect and clinical efficacy of daratumumab in a patient with cold agglutinin disease |
| topic | cold agglutinin disease daratumumab cytokines autoimmune diseases anti-CD38 MoAb |
| url | https://www.frontiersin.org/articles/10.3389/fimmu.2021.649441/full |
| work_keys_str_mv | AT annazaninoni theimmunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT juriagiannotta theimmunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT annagalli theimmunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT rosangelaartuso theimmunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT paolabianchi theimmunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT lucamalcovati theimmunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT lucamalcovati theimmunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT wilmabarcellini theimmunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT brunofattizzo theimmunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT annazaninoni immunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT juriagiannotta immunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT annagalli immunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT rosangelaartuso immunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT paolabianchi immunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT lucamalcovati immunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT lucamalcovati immunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT wilmabarcellini immunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease AT brunofattizzo immunomodulatoryeffectandclinicalefficacyofdaratumumabinapatientwithcoldagglutinindisease |