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Excellent response to anti-CD38 therapy with daratumumab in a patient with severe refractory CANOMAD
  1. Elba Pascual-Goñi1,
  2. Roger Collet1,
  3. Clara Tejada-Illa1,
  4. Lorena Martín-Aguilar1,
  5. Marta Caballero-Ávila1,
  6. Cinta Lleixà1,
  7. Silvana Novelli2,
  8. Jordi López-Pardo2,
  9. Albert Esquirol Sanfeliu2,
  10. Anais Mariscal3,
  11. Yolanda Álvaro Gargallo3,
  12. Eugenia Martínez-Hernández4,
  13. Dolores Cocho5,
  14. Luis Querol1
  1. 1 Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain
  2. 2 Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
  3. 3 Immunology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain
  4. 4 Department of Neurology, Hospital Clinic, Universitat de Barcelona, Barcelona, Spain
  5. 5 Department of Neurology, Hospital General de Granollers, Granollers, Spain
  1. Correspondence to Dr Elba Pascual-Goñi, Neurology, Hospital de la Santa Creu i Sant Pau, Barcelona 08041, Spain; epascualg{at}santpau.cat

Abstract

Background Intravenous 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.

Methods A 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.

Results After 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.

Conclusions The 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.

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Footnotes

  • Contributors EPG contributed to acquisition of data, collected the samples, analysed the data and drafted the manuscript for intellectual content. RC, CT-I and MC-A contributed to acquisition of data and revised the manuscript for intellectual content. LM-A, CL, AM and YAG helped to perform the experiments and revised the manuscript for intellectual content. EM-H, SN, JL-P, AES and DC revised the manuscript for intellectual content. LQ interpreted the data and revised the manuscript for intellectual content.

  • Funding This study was funded by GBS/CIDP Foundation International (Benson Fellowship personal grant to EPG).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.