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Daratumumab and Darbepoetin for Refractory Warm Autoimmune Hemolytic Anemia: A Novel Duo for a Tough Case
Background
Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.
Case Presentation
A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.
Discussion
The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.
Conclusions
Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.
Background
Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.
Case Presentation
A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.
Discussion
The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.
Conclusions
Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.
Background
Warm autoimmune hemolytic anemia (wAIHA) is traditionally treated with immunosuppresimmunosuppression, and management of refractory disease is often a challenge. The anti-CD38 antibody daratumumab is emerging as a promising treatment for refractory wAIHA, as it targets autoantibody-producing plasma cells. Here, we present the first reported case of daratumumab used in conjunction with an erythropoiesisstimulating agent (ESA) to salvage refractory wAIHA in a patient with AIDS and bone marrow suppression.
Case Presentation
A middle aged man with HIV (undetectable viral load on antiretroviral treatment but CD4 persistently < 200, requiring chronic antimicrobial prophylaxis) was diagnosed with classic wAIHA in late 2021. The disease initially responded to corticosteroids, but relapsed repeatedly and eventually required IVIG, rituximab, danazol, and three immunosuppressive agents, none of which induced remission. Hemolysis worsened by fall 2024, with hemoglobin 5-6 g/dL despite high-dose corticosteroids and IVIG. Bone marrow biopsy was unrevealing, and he underwent splenectomy. However, recovery was complicated by cutaneous nocardiosis, iron overload, liver injury, and continued hemolysis. Eventually, reticulocytosis also ceased, and hemoglobin declined to 4-5 g/dL. Due to failure of standard therapies and to minimize further immunosuppression, weekly daratumumab injections were initiated, with weekly darbepoetin injections added to aid in compensatory hematopoiesis. With this combination, hemolysis indices improved, reticulocytosis picked up, and hemoglobin increased to 8-9 g/dL. However, the patient continued to struggle with infections, and he succumbed to drug-resistant bacterial sepsis in spring 2025.
Discussion
The patient had very complicated chronic and acute comorbidities, and some simplification was required in order to provide this summary. However, we hope this case adds to the literature on daratumumab as an effective new agent in refractory wAIHA, and also present a novel duo of therapies for patients who may struggle with bone marrow suppression in addition to autoimmune hemolysis. To our knowledge, this is the first reported case of the combination used in this manner.
Conclusions
Daratumumab is an effective and less immunosuppressive alternative for the treatment of heavily pretreated refractory wAIHA. Its combined use with ESA in patients with inadequate reticulocytosis should be studied further to clarify the efficacy and safety in this setting.