慢性球状ニューロパチーとザヌブルチニブに反応するジシアル酸抗体

To describe a patient with chronic ataxic neuropathy with disialosyl antibodies (CANDA) with clinical and neurophysiological improvement after zanubrutinib therapy.

A 62-year-old man started complaining of sensory symptoms in his hands and feet extending over time to the knees and elbows. Nerve conduction studies were consistent with diffuse sensory axonal ganglionopathy. Blood tests revealed an IgM 𝜆 paraprotein expression of Waldenström's macroglobulinemia. Anti-MAG and anti-neuronal antibodies were negative. Anti-ganglioside IgM antibodies (GD1b; GD2, GD3, GT1a, GT1b, GQ1b) were positive. Neurological examination disclosed pinprick and tactile hypoesthesia with stocking-glove distribution. The patient was responsive to intravenous immunoglobulin (IVIg) but reported end-dose fluctuations. Rituximab was started but soon discontinued for clinical worsening, so IVIg therapy was resumed.

The patient was started on zanubrutinib, a second generation Bruton's tyrosine kinase (BTK) inhibitor, while continuing IVIg with global improvement and absence of end of dose efficacy. After 15 months, besides a clinical and hematological amelioration, a dramatic neurophysiological improvement also occurred. Antibodies to IgM GM1 and GM2 were not detectable, whereas anti-disialosyl antibodies GD1a and GD1b persisted unchanged.

To the best of our knowledge, this is the first patient with Waldenström-associated CANDA with clinical, hematological, and neurophysiological benefit after zanubrutinib therapy.