Daratumumab for treatment-refractory acquired idiopathic pure red cell aplasia

Abstract

Acquired pure red cell aplasia (PRCA) is a heterogenous entity, which may present in association with autoimmune diseases, lymphoproliferative disorders including large granular lymphocytic leukemia (LGL) or chronic lymphocytic leukemia (CLL), monoclonal gammopathy of undetermined significance (MGUS), thymoma, viral infections (parvovirus B19), drugs (recombinant erythropoietin), or ABO-incompatible stem cell transplantation. Accordingly, immunosuppressive agents are utilized as first line therapy and cyclosporine in combination with corticosteroids yields high response rates (66-95%). 2 Treatment considerations in refractory cases, include cyclophosphamide, alemtuzumab, antithymocyte globulin, bortezomib, rituximab, and intravenous immunoglobulin (IVIG). 1 Herein, we describe a 74-year-old female with a 10-year history of treatment-refractory idiopathic acquired PRCA with rapid and sustained response to daratumumab. At initial presentation, she developed symptomatic anemia (hemoglobin 5 g/dL, mean coruscular volume [MCV] 98% fL) requiring hospitalization. Anemia workup revealed severe reticulocytopenia, with reticulocyte percentage <0.28 and an absolute reticulocyte count of 2,800. Serology for parvovirus B19, cytomegalovirus, hepatitis B, C, and human immunodeficiency virus were negative. Monoclonal protein studies identified an IgG , 0.5 g/dL with a normal immunoglobulin free light chain ratio. Computed tomography scan of the chest showed no evidence of thymoma. Bone marrow (BM) examination revealed maturation arrest in erythroid precursors, few pro-normoblasts were seen, granulopoiesis and megakaryocytes appeared normal, and an increase in plasma cells (5%) was noted. There was neither evidence of a lymphoproliferative disorder nor myelodysplastic syndrome. Chromosome analysis and T-cell gene rearrangement studies were within normal limits. A diagnosis of idiopathic PRCA was established and the patient was initiated on cyclosporine and prednisone 60 mg daily with a 3-month taper. After 6 months of cyclosporine, given the ongoing transfusion needs, she received rituximab 375 mg/m 2 weekly for four doses without clinical response. Thereafter, a combination of anti-thymocyte globulin (ATG), cyclosporine and prednisone were administered, and 3 months later treatment was switched to alemtuzumab, followed by cyclophosphamide orally for 6 months which was discontinued due to treatment emergent neutropenia. Next, a trial of bor-

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