The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease

Zaninoni, Anna; Giannotta, Juri Alessandro; Gallì, Anna; Artuso, Rosangela; Bianchi, Paola; Malcovati, Luca; Barcellini, Wilma; Fattizzo, Bruno

doi:10.3389/fimmu.2021.649441

Cited by 26 publications

(27 citation statements)

References 35 publications

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“…Finally, several cases of SLE, RA, vasculitis, AH and aVWS complicating MM and amyloidosis have been reported [37,41]. As in LPD, the pathogenic association of MM plasma cells and autoantibody production paved the way to the use of anti-MM agents, including proteasome inhibitors and anti-CD38 antibodies [48,49].…”

Section: Aid In Other Lpdmentioning

confidence: 99%

Autoimmune Complications in Hematologic Neoplasms

Barcellini

Giannotta

Fattizzo

2021

Cancers

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Autoimmune cytopenias (AICy) and autoimmune diseases (AID) can complicate both lymphoid and myeloid neoplasms, and often represent a diagnostic and therapeutic challenge. While autoimmune hemolytic anemia (AIHA) and immune thrombocytopenia (ITP) are well known, other rarer AICy (autoimmune neutropenia, aplastic anemia, and pure red cell aplasia) and AID (systemic lupus erythematosus, rheumatoid arthritis, vasculitis, thyroiditis, and others) are poorly recognized. This review analyses the available literature of the last 30 years regarding the occurrence of AICy/AID in different onco-hematologic conditions. The latter include chronic lymphocytic leukemia (CLL), lymphomas, multiple myeloma, myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), myeloproliferative neoplasms, and acute leukemias. On the whole, AICy are observed in up to 10% of CLL and with higher frequencies in certain subtypes of non-Hodgkin lymphoma, whilst they occur in less than 1% of low-risk MDS and CMML. AID are described in up to 30% of myeloid and lymphoid patients, including immune-mediated hemostatic disorders (acquired hemophilia, thrombotic thrombocytopenic purpura, and anti-phospholipid syndrome) that may be severe and fatal. Additionally, AICy/AID are found in about 10% of patients receiving hematopoietic stem cell transplant or treatment with new checkpoint inhibitors. Besides the diagnostic difficulties, these AICy/AID may complicate the clinical management of already immunocompromised patients.

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Section: Aid In Other Lpdmentioning

confidence: 99%

Autoimmune Complications in Hematologic Neoplasms

Barcellini

Giannotta

Fattizzo

2021

Cancers

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“…In the last decade, several strategies to handle with autoimmune or alloimmune pathologic situations include CD38 antibodies (71)(72)(73).…”

Section: Cd38 Antibodies In Solid Organ Transplantation Cd38 Antibodies In Non Tumoral Contextmentioning

confidence: 99%

“…In the last decade, several strategies to handle with autoimmune or alloimmune pathologic situations include CD38 antibodies ( 71 – 73 ). Indeed, long-lived plasma cells, which produce pathogenic antibodies, are unresponsive to standard immunosuppression.…”

Section: Cd38 Antibodies In Solid Organ Transplantationmentioning

confidence: 99%

HLA Desensitization in Solid Organ Transplantation: Anti-CD38 to Across the Immunological Barriers

2021

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The presence of anti-human leucocyte antigen (HLA) antibodies in the potential solid organ transplant recipient’s blood is one of the main barriers to access to a transplantation. The HLA sensitization is associated with longer waitlist time, antibody mediated rejection and transplant lost leading to increased recipient’s morbidity and mortality. However, solid organ transplantation across the HLA immunological barriers have been reported in recipients who were highly sensitized to HLA using desensitization protocols. These desensitization regimens are focused on the reduction of circulating HLA antibodies. Despite those strategies improve rates of transplantation, it remains several limitations including persistent high rejection rate and worse long-term outcomes when compare with non-sensitized recipient population. Currently, interest is growing in the development of new desensitization approaches which, beyond targeting antibodies, would be based on the modulation of alloimmune pathways. Plasma cells appears as an interesting target given their critical role in antibody production. In the last decade, CD38-targeting immunotherapies, such as daratumumab, have been recognized as a key component in the treatment of myeloma by inducing an important plasma cell depletion. This review focuses on an emerging concept based on targeting CD38 to desensitize in the field of transplantation.

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“…Daratumumab binds to CD38 expressed on plasma cells and is cytolytic for these cells. Small case studies of patients with APS, SLE, and autoimmune hematologic conditions report that treatment with daratumumab reduces autoantibody production in concert with improved clinical manifestations of disease (70)(71)(72), providing the rationale for the ITN study of daratumumab therapy in APS with the goal of eliminating antiphospholipid antibodies.…”

Section: Autoimmunitymentioning

confidence: 99%

Approaches to Establishing Tolerance in Immune Mediated Diseases

et al. 2021

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The development of rational approaches to restore immune tolerance requires an iterative approach that builds on past success and utilizes new mechanistic insights into immune-mediated pathologies. This article will review concepts that have evolved from the clinical trial experience of the Immune Tolerance Network, with an emphasis on lessons learned from the innovative mechanistic studies conducted for these trials and new strategies under development for induction of tolerance.

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The Immunomodulatory Effect and Clinical Efficacy of Daratumumab in a Patient With Cold Agglutinin Disease

Cited by 26 publications

References 35 publications

Autoimmune Complications in Hematologic Neoplasms

Autoimmune Complications in Hematologic Neoplasms

HLA Desensitization in Solid Organ Transplantation: Anti-CD38 to Across the Immunological Barriers

Approaches to Establishing Tolerance in Immune Mediated Diseases

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