Daratumumab, a monoclonal antibody, may merit consideration as a treatment for patients with severe refractory pulmonary and cutaneous ANCA-associated vasculitis (AAV), according to the authors of a recent case report.

B-cell depletion with anti-CD20 therapy is considered the standard of care, but some patients do not respond to it.

Research shows that long-lived plasma cells, which are unaffected by usual immunosuppressive therapies, maintain ANCA production, thereby leading to ongoing autoimmune inflammation, Torben M. Rixecker, MD, and colleagues at Saarland University Medical Center in Homburg, Germany, explained in a paper published in JAMA Internal Medicine.

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Daratumumab binds to CD38, which is highly expressed on long-lived plasma cells and overexpressed on multiple myeloma cells, according to the authors. They noted that daratumumab has shown benefit in patients with multiple myeloma and has been used to treat patients with systemic lupus erythematosus.

The case involved a man in his late 20s receiving care at Saarland University Medical Center in 2022. He initially presented with a cutaneous ulceration on his right foot and upper lobe predominant, centrilobular consolidations. During the entire course of disease, the patient did not have kidney involvement. Despite intensive immunosuppression, the patient’s disease progressed unimpeded. The patient required extracorporeal membrane oxygenation (ECMO) 67 days after hospital admission due to bronchoscopy-proven diffuse alveolar hemorrhage.

Three days after the patient started on ECMO, his physicians administered daratumumab according to protocols approved for multiple myeloma. The patient received daratumumab infusions at a dosage of 16 mg/kg once a week. The drug was added to oral cyclophosphamide, prednisolone, and avacopan. Eleven days following receipt of daratumumab, the patient’s ANCA titer became negative for the first time throughout his entire treatment course, according to the authors. As of January 2023, the patient remained in remission.

Dr Rixecker and colleagues explained that in ANCA-associated vasculitis, ANCAs are believed to contribute to the pathogenesis of the disease. “If those autoantibodies are produced by long-lived plasma cells, the immunosuppressive therapies for [ANCA-associated vasculitis] that are usually administered may be ineffective.”

The authors concluded that “the clinical course and apparent response to daratumumab suggest that therapies targeting CD38 should be further studied for patients with severe refractory pulmonary and cutaneous [ANCA-associated vasculitis].”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Rixecker TM, Lepper PM, Mang S, et al. Daratumumab for a patient with refractory antineutrophil cytoplasmic antibody-associated vasculitis. JAMA Intern Med. Published online April 10, 2023. doi:10.1001/jamainternmed.2023.0152