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Daratumumab for treatment of pure red cell aplasia after allogeneic stem cell transplantation

Bone Marrow Transplantation volume 55, pages 1191–1193 (2020)Cite this article

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Pure red cell aplasia (PRCA) is a potential complication after allogeneic stem cell transplantation (allo-SCT), which results from AB0 blood-group incompatibility causing persistent recipient antibodies directed against donor red cells and occurs in 6–30% depending on the conditioning regimen. As a consequence, erythroid recovery is delayed after allo-SCT accompanied by a lack of erythroid precursors in bone marrow (BM) and no detectable reticulocytes in peripheral blood (PB). Patients suffering from PRCA require repeated red blood cell (RBC) transfusions and are at risk for transfusion-associated side effects [1, 2]. Currently, there is no defined standard for management of post-transplant PCRA but commonly used treatment approaches consist of erythropoiesis-stimulating agents, tapering of immunosuppression or donor lymphocyte infusions (DLI) to promote graft-versus-plasma-cell effect, steroids, Rituximab, and Bortezomib to suppress antibody-producing B cells and plasma cells as well as plasmapheresis to eliminate iso-hemagglutinins [1,2,3,4]. Still, these treatments are only effective in some patients and can be associated with relevant side effects. Searching for novel, effective, and well-tolerated approaches two groups recently reported on two patients suffering from PRCA after allo-SCT who were successfully treated with the IgG1k anti-CD38 monoclonal antibody Daratumumab [5, 6]. To collect further experience regarding this issue, we here describe the case of a third patient with post-transplant PRCA, who was successfully treated with Daratumumab.

In addition to the two recently reported cases [5, 6] our case reported here represents, to the best of our knowledge, the third patient with PRCA after allo-SCT which was successfully treated with Daratumumab. The optimal management of posttransplant PCRA is not clearly defined, but currently employed treatment approaches consist of tapering of immunosuppression, erythropoiesis-stimulating agents, steroids, Rituximab, Bortezomib, plasma exchange, and DLI [1,2,3,4]. Similar to the two previously reported cases, our patient had already failed tapering of immunosuppression and treatment with the anti-CD20 antibody Rituximab. The latter may be related to the fact that Rituximab only targets CD20+ mature B cells, but not CD20- plasma cells and plasmablasts. Weighting the expected benefit and risks such as neuropathy (Bortezomib), temporary effect (plasma exchange) and GvHD (DLI), we decided against these options and chose Daratumumab to selectively target the isohemagglutinin-producing, CD38-expressing plasma cells and plasmablasts. Of particular interest, response promptly started after the first dose and was sustained after a short course (2, 4, and 6 applications) of Daratumumab in all three patients without any further treatment. This supports the notion that Daratumumab seems to be an effective therapy for PRCA after allo-SCT, which may even be considered earlier in the course of treatment to avoid potential side effects of other less effective interventions. In a rare indication like post-transplant PRCA, where a prospective trial is unlikely to be performed, we believe that reporting these cases is important to gain evidence in order to help physicians to choose the most effective treatment and to convince health insurance providers to cover the costs of such an efficient approach even in the absence of an approval or data from a prospective trial. Furthermore, our as well as the two cases by Bathini et al. and Chapuy et al. suggest that Daratumumab may also be a considerable option to be investigated in other antibody-mediated hematologic diseases such as auto-immune hemolysis, as recently reported [7], or immune thrombocytopenia.

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Authors and Affiliations

  1. Department of Hematology, Oncology and Clinical Immunology, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany

    Christina Rautenberg, Jennifer Kaivers, Ulrich Germing, Rainer Haas, Guido Kobbe & Thomas Schroeder

  2. Institute for Transplantation Diagnostics and Cell Therapeutics, University Hospital Duesseldorf, Medical Faculty, Duesseldorf, Germany

    Stefanie Ackerstaff & Till Hoffmann

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  1. Christina Rautenberg
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  2. Jennifer Kaivers
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  3. Ulrich Germing
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Contributions

TS, CR, and GK treated the patient. SA and TH provided measurement of antibody-titers and blood-group typing. JK and UG provided interpretation and delivery of the images. TS and CR wrote the paper. All authors critically reviewed the paper.

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Correspondence to Thomas Schroeder.

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Rautenberg, C., Kaivers, J., Germing, U. et al. Daratumumab for treatment of pure red cell aplasia after allogeneic stem cell transplantation. Bone Marrow Transplant 55, 1191–1193 (2020). https://doi.org/10.1038/s41409-019-0664-4

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