Repeated Response to Daratumumab in Refractory MGUS-Associated Pure Red Cell Aplasia Persisting After Allogeneic...

Pure red cell aplasia (PRCA) is usually managed as a disorder driven predominantly by cellular immune mechanisms, but plasma cell-directed therapy may be relevant in selected cases associated with monoclonal gammopathy. We report a case of refractory PRCA associated with IgG-kappa monoclonal gammopathy of undetermined significance (MGUS). A 64-year-old woman remained transfusion-dependent despite multiple therapies and subsequently underwent allogeneic hematopoietic cell transplantation from an 8/8 HLA-matched unrelated donor. Despite prompt donor engraftment, PRCA persisted, and kappa-restricted plasma cells were detected in the bone marrow, although their recipient origin could not be confirmed by plasma cell-specific chimerism analysis. Daratumumab, bortezomib, and dexamethasone therapy, followed by daratumumab monotherapy, was associated with reticulocyte recovery, transfusion independence, disappearance of the monoclonal protein, and erythroid recovery in the bone marrow. Approximately 3 years and 3 months after discontinuation of daratumumab, anemia recurred with reappearance of M-protein and kappa-restricted plasma cells, and again improved after daratumumab monotherapy. This case supports the possibility that a plasma-cell-associated mechanism may contribute to PRCA in selected patients with monoclonal gammopathy and suggests that plasma cell-directed therapy may be considered before proceeding to allogeneic transplantation. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.