Daratumumab for Posttransplant Autoimmune Hemolytic Anemia

We read with great interest the recent article by Desai et al. [1], wherein the authors highlighted the emerging role of daratumumab in addressing complex immune-mediated cytopenias post allogeneic hematopoietic stem cell transplantation (HCT). The findings align with our own clinical experience, wherein we encountered a case of post HCT refractory warm autoimmune hemolytic anemia (AIHA). Our patient, a 21-year-old female, underwent allogeneic HCT for aplastic anemia from a 10/10 male matched unrelated donor, after cyclophosphamide, total body irradiation, and rabbit anti-thymocyte globulin-based conditioning regimen. Donor and recipient blood groups were matched. She remained on immunosuppressive therapy with tacrolimus, which was planned for 1 year after the transplant. She did not have any GVHD. Eleven months after transplant, while still on tacrolimus, she spontaneously developed warm AIHA(IgG positive). Secondary causes included infections such as EBV and were excluded. Initial treatment with high-dose prednisone(2 mg/kg/day) resulted in complete response and normalization of hemoglobin. Steroids were subsequently tapered gradually. However, at 0.25 mg/kg prednisone, she experienced a recurrence of AIHA with refractory hemolysis that necessitated intensive treatment with intravenous methylprednisolone 1 mg/kg IV daily, intravenous immunoglobulin (1 g/kg × 5 days), and Rituximab(375 mg/m2 weekly × 4 doses). Bone marrow biopsy performed was consistent with high cellular turnover and full donor chimerism. Given the refractory nature of her hemolysis, compassionate access to daratumumab was obtained. Following one cycle of four weekly doses, the patient demonstrated remarkable clinical improvement within 4 weeks (Figure 1) and hemoglobin stabilized at 131 g/L. She became transfusion independent approximately 4 weeks after daratumumab initiation and hemoglobin normalized within 8 weeks. There was significant correction of hemolytic markers and a negative antibody screen at the 6-month follow-up. She had mild wheezing and pruritis with her first dose, which responded to supportive care with no subsequent reactions. We were able to successfully taper steroids, without the need for further immunosuppressive therapies such as additional rituximab. Daratumumab's efficacy in the context of AIHA underscores its immunomodulatory role in depleting CD38-expressing plasma cells, thereby reducing autoantibody production [2]. This therapeutic approach has the potential to be valuable in posttransplant immune-mediated cytopenias, where standard immunosuppressive regimens often fail. While the role of daratumumab is well-established in multiple myeloma, its utility in HCT-associated immune complications, such as AIHA or red cell aplasia(PRCA), is gaining recognition as a second- or third-line agent [3, 4]. Daratumumab is also effective in post-transplant delayed red cell engraftment, which shares a similar pathophysiology, further supporting its potential use in refractory posttransplant AIHA [5]. AIHA is the most common autoimmune cytopenia after HCT, with an incidence of up to 6%, typically occurring 5–10 months after transplant [6]. Risk factors include pediatric age, unrelated or haploidentical donors, nonmalignant disorders, GVHD, infections, and CMV reactivation [7]. While several reports highlight the off-label use of daratumumab for autoimmune cytopenias in pediatric patients, data on its efficacy as monotherapy for AIHA in adults are limited [8, 9]. A recent international retrospective study of 19 adults with heavily pretreated refractory AIHA demonstrated some efficacy and safety of daratumumab monotherapy, although posttransplant patients were excluded [2]. In conclusion, our experience adds to the growing body of evidence supporting the role of daratumumab in treating refractory immune-mediated cytopenia postallogeneic HCT, including AIHA. Challenges such as cost, drug access and approval, availability of infusion clinics, and the need for close monitoring of immunosuppressive side effects remain barriers to widespread adoption. Further studies are warranted to establish standardized protocols and to define the role of daratumumab relative to other therapeutic options for post-HCT immune-mediated cytopenias, such as PRCA and AIHA. Y.A., R.V.N.: collection of data, review of literature. Y.A., M.K., A.M., R.V.N.: preparation of manuscript. The authors declare no conflicts of interest.

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