• Elba Pascual-Goñi, Roger Collet, Clara Tejada-Illa, Lorena Martín-Aguilar, Marta Caballero-Ávila, Cinta Lleixà, Silvana Novelli, Jordi López-Pardo, Albert Esquirol Sanfeliu, Anais Mariscal, Yolanda Álvaro Gargallo, Eugenia Martínez-Hernández, Dolores Cocho, and Luis Querol.
• Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain epascualg@santpau.cat.
• J. Neurol. Neurosurg. Psychiatr. 2024 Jun 17; 95 (7): 609611609-611.

BackgroundIntravenous immunoglobulin (IVIG) and rituximab are considered the first-line and second-line treatments for Chronic Ataxic Neuropathy and Ophthalmoplegia with IgM-paraprotein, cold Agglutinins, and anti-Disialosyl antibodies (CANOMAD), with an overall clinical response around 50%. New anti-CD38 daratumumab, targeting long-lived plasma cells, has been reported as a promising therapy for treatment-refractory antibody-mediated disorders. We report the first case of a severe refractory CANOMAD, successfully treated with daratumumab.MethodsA patient in their 70s with severe relapsing CANOMAD, refractory to IVIG, steroids, rituximab and ibrutinib developed severe tetraparesis and respiratory failure. Plasma exchange (PE) improved motor and ventilatory function; however, after 6 weeks, patient remained PE dependent. Intravenous daratumumab was initiated at 16 mg/kg weekly for 3 weeks, every 2 weeks for the second and third month, and monthly afterwards.ResultsAfter 3 weeks of starting daratumumab, PE was discontinued and, since then, the patient evolved to complete recovery. Antidisialosyl antibody titres decreased after PE and remained stable during daratumumab. Serum neurofilament light-chain levels were elevated in the exacerbation phase and normalised after daratumumab. The patient remains in clinical remission under monthly daratumumab, 12 months after initiation.ConclusionsThe first patient with aggressive treatment-refractory CANOMAD treated with daratumumab provides proof-of-principle evidence that daratumumab may be an effective treatment in IgM-related neuropathies.© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.

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