PMID- 38341197
OWN - NLM
STAT- Publisher
LR  - 20240210
IS  - 1468-330X (Electronic)
IS  - 0022-3050 (Linking)
DP  - 2024 Feb 10
TI  - Excellent response to anti-CD38 therapy with daratumumab in a patient with severe 
      refractory CANOMAD.
LID - jnnp-2023-332443 [pii]
LID - 10.1136/jnnp-2023-332443 [doi]
AB  - 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.
CI  - (c) Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and 
      permissions. Published by BMJ.
FAU - Pascual-Goni, Elba
AU  - Pascual-Goni E
AUID- ORCID: 0000-0001-7336-4305
AD  - Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i 
      Sant Pau, Barcelona, Spain epascualg@santpau.cat.
FAU - Collet, Roger
AU  - Collet R
AD  - Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i 
      Sant Pau, Barcelona, Spain.
FAU - Tejada-Illa, Clara
AU  - Tejada-Illa C
AD  - Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i 
      Sant Pau, Barcelona, Spain.
FAU - Martin-Aguilar, Lorena
AU  - Martin-Aguilar L
AUID- ORCID: 0000-0002-1553-2224
AD  - Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i 
      Sant Pau, Barcelona, Spain.
FAU - Caballero-Avila, Marta
AU  - Caballero-Avila M
AUID- ORCID: 0000-0001-9850-8504
AD  - Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i 
      Sant Pau, Barcelona, Spain.
FAU - Lleixa, Cinta
AU  - Lleixa C
AD  - Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i 
      Sant Pau, Barcelona, Spain.
FAU - Novelli, Silvana
AU  - Novelli S
AD  - Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat 
      Autonoma de Barcelona, Barcelona, Spain.
FAU - Lopez-Pardo, Jordi
AU  - Lopez-Pardo J
AD  - Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat 
      Autonoma de Barcelona, Barcelona, Spain.
FAU - Sanfeliu, Albert Esquirol
AU  - Sanfeliu AE
AD  - Department of Haematology, Hospital de la Santa Creu i Sant Pau, Universitat 
      Autonoma de Barcelona, Barcelona, Spain.
FAU - Mariscal, Anais
AU  - Mariscal A
AD  - Immunology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma 
      de Barcelona, Barcelona, Spain.
FAU - Alvaro Gargallo, Yolanda
AU  - Alvaro Gargallo Y
AD  - Immunology Department, Hospital de la Santa Creu i Sant Pau, Universitat Autonoma 
      de Barcelona, Barcelona, Spain.
FAU - Martinez-Hernandez, Eugenia
AU  - Martinez-Hernandez E
AUID- ORCID: 0000-0002-8317-7068
AD  - Department of Neurology, Hospital Clinic, Universitat de Barcelona, Barcelona, 
      Spain.
FAU - Cocho, Dolores
AU  - Cocho D
AD  - Department of Neurology, Hospital General de Granollers, Granollers, Spain.
FAU - Querol, Luis
AU  - Querol L
AUID- ORCID: 0000-0002-4289-8264
AD  - Neuromuscular Diseases Unit, Department of Neurology, Hospital de la Santa Creu i 
      Sant Pau, Barcelona, Spain.
LA  - eng
PT  - Journal Article
DEP - 20240210
PL  - England
TA  - J Neurol Neurosurg Psychiatry
JT  - Journal of neurology, neurosurgery, and psychiatry
JID - 2985191R
SB  - IM
OTO - NOTNLM
OT  - NEUROPATHY
COIS- Competing interests: None declared.
EDAT- 2024/02/11 07:42
MHDA- 2024/02/11 07:42
CRDT- 2024/02/10 20:53
PHST- 2023/08/22 00:00 [received]
PHST- 2023/11/01 00:00 [accepted]
PHST- 2024/02/11 07:42 [medline]
PHST- 2024/02/11 07:42 [pubmed]
PHST- 2024/02/10 20:53 [entrez]
AID - jnnp-2023-332443 [pii]
AID - 10.1136/jnnp-2023-332443 [doi]
PST - aheadofprint
SO  - J Neurol Neurosurg Psychiatry. 2024 Feb 10:jnnp-2023-332443. doi: 
      10.1136/jnnp-2023-332443.