Daratumumab monotherapy in refractory warm autoimmune hemolytic anemia and cold agglutinin disease

Marit Jalink*, Chaja F. Jacobs, Jahanzaib Khwaja, Dorothea Evers, Coty Bruggeman, Bruno Fattizzo, Marc Michel, Etienne Crickx, Quentin A. Hill, Ulrich Jaeger, Arnon P. Kater, Anja B.U. Mäkelburg, Anouk Breedijk, Peter A.W. te Boekhorst, Marlijn P.A. Hoeks, Masja de Haas, Shirley D’Sa, Josephine M.I. Vos

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

4 Citations (Scopus)
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Abstract

Autoimmune hemolytic anemia (AIHA) is a rare autoantibody-mediated disease. For steroid and/or rituximab-refractory AIHA, there is no consensus on optimal treatment. Daratumumab, a monoclonal antibody targeting CD38, could be beneficial by suppression of CD38+ plasma cells and thus autoantibody secretion. In addition, because CD38 is also expressed by activated T cells, daratumumab may also act via immunomodulatory effects. We evaluated the efficacy and safety of daratumumab monotherapy in an international retrospective study including 19 adult patients with heavily pretreated refractory AIHA. In warm AIHA (wAIHA, n = 12), overall response was 50% with a median response duration of 5.5 months (range, 2-12), including ongoing response in 2 patients after 6 and 12 months. Of 6 nonresponders, 4 had Evans syndrome. In cold AIHA (cAIHA, n = 7) overall hemoglobin (Hb) response was 57%, with ongoing response in 3 of 7 patients. One additional patient with nonanemic cAIHA was treated for severe acrocyanosis and reached a clinical acrocyanosis response as well as a Hb increase. Of 6 patients with cAIHA with acrocyanosis, 4 had improved symptoms after daratumumab treatment. In 2 patients with wAIHA treated with daratumumab, in whom we prospectively collected blood samples, we found complete CD38+ T-cell depletion after daratumumab, as well as altered T-cell subset differentiation and a severely diminished capacity for cell activation and proliferation. Reappearance of CD38+ T cells coincided with disease relapse in 1 patient. In conclusion, our data show that daratumumab therapy may be a treatment option for refractory AIHA. The observed immunomodulatory effects that may contribute to the clinical response deserve further exploration.

Original languageEnglish
Pages (from-to)2622-2634
Number of pages13
JournalBlood Advances
Volume8
Issue number11
DOIs
Publication statusPublished - 11 Jun 2024

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© 2024 by The American Society of Hematology.

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