Daratumumab for the treatment of refractory ANCA-associated vasculitis

Abstract

ObjectiveTreatment-refractory antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a life-threatening condition without evidence-based treatment options. One emerging treatment option for several antibody-mediated autoimmune diseases is the anti-CD38 antibody daratumumab, which depletes autoantibody-secreting plasma cells.MethodsWe treated two patients with severe life-threatening AAV with renal and pulmonary manifestation despite induction therapy with rituximab and cyclophosphamide with four to eight doses of 1800 mg daratumumab. We followed clinical and immunological responses.ResultsThe first patient with myeloperoxidase-ANCA-positive microscopic polyangiitis had resolution of pneumonitis and pleuritis and stabilisation of kidney function after daratumumab. The second patient with proteinase 3-ANCA-positive granulomatosis with polyangiitis, diffuse alveolar haemorrhage necessitating extracorporeal membrane oxygenation (ECMO) and acute kidney failure, requiring kidney replacement therapy, was weaned off ECMO, mechanical ventilation and dialysis and discharged home after daratumumab. Clinical improvement was paralleled by a strong reduction in serum ANCA levels as well as total IgG, indicating depletion of plasma cells. Apart from the depletion of CD38+natural killer cells, blood leucocyte levels were not notably influenced by daratumumab. Only mild adverse events, such as hypogammaglobulinaemia and an upper respiratory tract infection occurred.ConclusionDaratumumab was safe and effective in inducing remission in two patients with severe treatment-refractory AAV, warranting prospective clinical trials to establish safety and efficacy.

Successful Desensitization with Imlifidase and Daratumumab in a Highly Immunized, Crossmatch Positive, Blood Group-Incompatible Living-Donor Re-Transplant Recipient with Systemic Lupus Erythematosus and Antiphospholipid Syndrome

“…Catastrophic APS is a rare and live-threatening antibody-mediated disease [ 17 ] which is so far mainly treated with plasma exchange, especially in this indication, imlifidase could be a new promising approach. The concept of targeting plasma cells with daratumumab has already been described in several other indications such as SLE [ 18 ], ANCA-associated vasculitis [ 19 ], and autoantibody-driven neurological autoimmune diseases [ 20 ], while larger studies and studies on long-term effects are still missing. Here we report the combination of imlifidase and daratumumab in a multimodal treatment regimen for a patient with APS, demonstrating the profound effect of this combination on APS and SLE autoantibodies.…”

B-cell targeting with anti-CD38 daratumumab: implications for differentiation and memory responses

“…Apart from its approval for MM treatment, CD38-targeting mAb DARA is gaining attraction as a rescue therapy for autoimmune conditions with PC involvement (Table S1). Hitherto, the promising evidence for DARA as a therapeutic option in autoimmune diseases is based exclusively on individual case reports ( 47 ). How anti-CD38 therapy influences normal PCs or PC differentiation beyond depletion in cancer settings has remained virtually unexplored.…”

CD38 als innovatives therapeutisches Target zur Plasmazelldepletion bei Autoimmunerkrankungen

“…Sie beinhalten therapierefraktäre Fälle (durchschnittlich 5 verschiedene vorangegangene Therapien) bei 24 verschiedenen Autoimmunkrankheiten. Rheumatologische Indikationen mit positiven Ergebnissen umfassen ANCA-assoziierte Vaskulitis (AAV) 14 , 15 , idiopathisch-inflammatorische Myopathie (IIM) 16 , 17 sowie Sjögren-Syndrom 18 . Zusätzlich standen auch hämatologische, nephrologische und neurologische Erkrankungen im Fokus ( Tab.…”