Case Report: Resetting the Humoral Immune Response by Targeting Plasma Cells With Daratumumab in Anti-Phospholipid Syndrome

Abstract

IntroductionMonoclonal antibodies (mAb) targeting plasma cells are malignant gammopathy designed and approved therapies. In recent years, these antibodies have also been increasingly introduced for non-malignant conditions such as autoimmune-mediated diseases. The Anti-Phospholipid Syndrome (APS) is an immune-mediated disorder in which autoantibodies against phospholipid associated proteins could elicit the activation of the coagulation cascade in specific situations. Therefore, the mainstream treatment for APS patients is the use of anticoagulant therapy. However, there are refractory patients who would benefit from targeting the antibodies rather than their effects. Rituximab, a B-cell depleting mAb, and intravenous immunoglobulins (IVIG) have been used in APS patients without showing a clear beneficial effect or a significant drop in anti-phospholipid antibody (aPL) levels.Clinical caseWe present our first APS case treated with daratumumab, an anti-CD38 mAb, in a 21-year-old patient with APS who presented with recurrent venous thromboembolic events despite adequate anticoagulant therapy. She tested positive for lupus anticoagulant, anti-cardiolipin IgG, anti-beta-2-glycoprotein-I IgG and anti-phosphatidylserine/prothrombin IgG and IgM. She was administered one dose weekly of daratumumab for 4 weeks. The treatment showed an adequate safety profile and was well tolerated. The patient was discharged after undergoing a clinically significant improvement. After the therapy, her levels of positive aPL declined significantly and most continued to decrease during the next three months. The patient experienced a new thrombotic episode two years after the therapy associated with poor adherence to antithrombotic therapy.ConclusionsThe treatment with daratumumab showed an adequate safety profile, was well tolerated and led to a significant clinical improvement. Levels of aPL lowered on therapy and the next three months and then rose again during follow-up. Further investigation is needed to better elucidate the role and optimal timing and doses of daratumumab in treatment of refractory APS.

B-Cells and BAFF in Primary Antiphospholipid Syndrome, Targets for Therapy?

“…To date, one case report described the use of daratumumab in addition to plasmapheresis and IVIG in a patient with PAPS with recurrent thrombotic events under adequate anticoagulant treatment. After starting daratumumab, the numbers of circulating plasmablasts, and levels of IgG aCL and IgG aβ2GPI declined, starting to reappear after approximately 4 months and no recurrent thrombotic events occurred in the following two years of follow-up [70].…”

“…Various "non-criteria" manifestations including thrombocytopenia [61,62,64,65] Thrombosis recurrence [61,63,65] Catastrophic APS [61,65,66] Daratumumab Thrombosis recurrence (case report) [70] Belimumab Diffuse alveolar hemorrhage (case report) [71] Skin ulcers (case report) [71] Catastrophic APS (case report)…”

Antiphospholipid syndrome: advances in diagnosis, pathogenesis, and management

“…Other agents that might warrant further study include sirolimus, 184 adenosine receptor agonists such as dipyridamole, 154 and plasma cell depleting agents such as daratumumab. 262 Patients are also interested in further study of supplements such as CoQ10, ginger, and vitamin D that have shown promise in preclinical and mechanistic studies. 156 263 264 A review of clinicaltrials.gov in September 2022 identified antiphospholipid syndrome trials recruiting subjects for interventions targeting B cells (belimumab, telitacicept, zanubrutinib), tumor necrosis factor (certolizumab), and innate immunity (hydroxychloroquine).…”

Antiphospholipid syndrome management: a 2023 update and practical algorithm-based approach

“…A notable decline in aCL IgG and aβ2GPI IgG persisted for 108 days after the first dose of medication. Significant clinical improvement was noted after 4 weeks of treatment [96 ▪ ]. Notably, the Daratumumab in Primary Antiphospholipid Syndrome (DARE-APS) trial was recently launched.…”