Case Report: Daratumumab for a Patient With Refractory Systemic Lupus Erythematosus and Antiphospholipid Syndrome Presenting as Thrombocytopenia

Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder, often characterized by thrombocytopenia, particularly when accompanied by antiphospholipid syndrome (APS), which is frequently associated with elevated levels of antiphospholipid antibodies (aPL) [1]. Recent research has increasingly highlighted the role of long-circulating plasma cells, which secrete pathogenic antibodies, in the pathogenesis of SLE. Daratumumab, a monoclonal antibody targeting CD38, has emerged as a promising therapeutic option for autoimmune diseases, specifically by depleting malignant plasma cells. This case report discusses a patient with refractory SLE and APS, presenting with thrombocytopenia, with the aim of evaluating the clinical outcomes and therapeutic potential of daratumumab in this context. A 54-year-old female patient presented with refractory thrombocytopenia for over a year despite being treated with high-dose steroids along with mycophenolate mofetil (MMF), cyclosporine A (CsA), and intravenous immunoglobulin (IVIG). She was diagnosed with SLE and APS 12 years ago. Previous therapies (Figure 1) failed to induce sustainable remission. Upon admission, the physical examination revealed scattered ecchymosis on both lower limbs. Laboratory tests showed a platelet count of 21 × 109/L, elevated antinuclear antibody (ANA) titers, and positive results for anti–double–stranded DNA (anti-dsDNA), anti-RO52, anti-SSA, anti-ribosomal P-protein antibodies, IgA anti-cardiolipin antibodies, IgM anti-β2 glycoprotein I antibodies, as well as IgG and IgM anti-phosphatidylserine/prothrombin antibodies. Additionally, platelet-associated antibodies, including anti-GP IIb/IIIa, anti-GP IX, and anti-GMP antibodies, were detected. Furthermore, the levels of lupus anticoagulant (LA), D-dimer, and fibrin degradation products (FDPs) were markedly elevated. These findings suggested that the thrombocytopenia may have resulted from a synergistic combination of immune-mediated platelet destruction and in vivo microthrombosis. Flow cytometry revealed a marked increase in CD38-positive plasma cells in peripheral blood. Following this, the patient received daratumumab at a dose of 4 mg/kg via intravenous infusion every 2 weeks for 1 month. After a 4-week treatment, the patient's platelet count increased from 21 × 109/L to 107 × 109/L. The SLE Disease Activity Index 2000 (SLEDAI-2 K) score decreased from 18 to 6 and remained stable over the subsequent year. Furthermore, the patient's erythrocyte sedimentation rate (ESR), C3, C4, and immunoglobulin levels normalized (Figure 1A–E). Coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), D-Dimer, fibrin degradation products (FDPs), and lupus anticoagulant (LA) returned to the normal range. Daratumumab was well-tolerated, with no adverse reactions observed (Figure 1F). In addition, the ratio of lymphocyte subsets in the patient showed some changes after treatment (Figure 1G). The results indicate a slight decrease in the ratio of B lymphocyte subsets, which is consistent with the depletion of CD38-positive plasma cells (Figure 1H). In this case, daratumumab was used for the first time at a low dose to treat thrombocytopenia secondary to refractory SLE and APS in a low dose, referred to as “mini-dara.” With “mini-dara,” thrombocytopenia caused by both immune-mediated destruction and microthrombosis was successfully corrected. Flow cytometry revealed a high proportion of CD38-positive plasma cells in peripheral blood (CD38+ plasma cell/B cell ratio of 73.64%). Following treatment with mini-dara, CD38+ plasma cells were undetectable, indicating that low-dose daratumumab effectively depleted these specific plasma cells expressing CD38. Notably, the patient maintained sustained remission during the subsequent 1-year follow-up period. CD38 (Cluster of Differentiation 38) is a multifunctional transmembrane glycoprotein that is predominantly expressed on the surface of plasma cells [2]. Daratumumab, the first monoclonal antibody targeting CD38, was initially approved for the treatment of multiple myeloma. Due to its capacity to induce plasma cell depletion, it has since been investigated for reducing pathogenic autoantibodies by targeting and depleting long-lived plasma cells, thereby offering a potential strategy for the management or treatment of refractory autoimmune disorders. Daratumumab has demonstrated efficacy in reducing venous thromboembolic events in patients with APS by lowering antiphospholipid antibody titers [3], and it also shows promise as a therapeutic option for refractory immune thrombocytopenia (ITP) through the reduction of anti-GP IIb/IIIa antibody levels [4] In the treatment of SLE, the depletion of circulating plasma cells by daratumumab underscores its therapeutic potential in targeting antibody-producing plasma cells. Additionally, SLE patients with elevated levels of interferon (IFN)-alpha show significant defects in hematopoiesis [5]. In two reported cases of SLE treated with daratumumab, the treatment effectively led to significant symptom amelioration in patients [6] and a sustained remission in the subsequent 3-year follow-up [7], which was associated with a reduction in type I IFN activity. In addition, daratumumab has demonstrated promising therapeutic potential in other antibody-mediated autoimmune diseases, such as refractory primary Sjögren disease, refractory ANCA-associated vasculitis, and myositis. Clinical reports indicate that after one or two cycles of daratumumab, patients achieved remission of clinical symptoms, with stabilization observed during follow-up periods ranging from 3 months to 3 years. Here we summarize the characteristics and outcomes of these patients (Table 1). Regarding its impact on other lymphocyte subsets, daratumumab may exert therapeutic effects through interactions with T or NK cells, in addition to its primary action on plasma cells, as indicated by these case reports. In the context of APS treatment, no significant changes were observed in B-cell and overall lymphocyte levels following daratumumab administration. However, a transient decrease in NK-cell levels was noted, which mirrors findings observed in our case. While most cases demonstrated significant disease remission after treatment, complete recovery was not achieved, which may be attributed to the course and dosage of daratumumab. Future prospective clinical trials are necessary to evaluate the safety and efficacy of daratumumab in patients with autoimmune diseases, to define optimal treatment regimens, and to identify the most suitable patient populations. Xinyu Li: writing – original draft, methodology, investigation, data curation. Xuesong Liu: writing – review and editing, formal analysis, visualization. Hanlin Yin: conceptualization, validation, writing – review and editing, corresponding author. Liangjing Lu: writing – review and editing, supervision, project administration, resources, corresponding author. We thank the patient for granting permission to publish this information. The authors declare no conflicts of interest. The authors confirm that the data supporting the findings of this study are available within the article.