Treatment of paraneoplastic neurological syndromes with antineuronal antibodies (Anti-Hu, Anti-Yo) with a combination of immunoglobulins, cyclophosphamide, and methylprednisolone

TLDR

The study assessed whether combined IVIg, cyclophosphamide, and methylprednisolone improves the clinical course of patients with paraneoplastic neurological syndrome and anti‑Hu or anti‑Yo antibodies. Seventeen patients received 1–9 cycles (mean 3.5) of IVIg 0.5 g/kg/day for 5 days, cyclophosphamide 600 mg/m² on day 1, and methylprednisolone 1 g/day for 3 days, with response evaluated by the Rankin scale and defined as improvement or stabilization for ambulatory patients and only improvement for bedridden patients. The regimen was well tolerated with no grade 3/4 toxicity; among 16 evaluable patients, none of the 7 severely disabled improved, while 3 of 9 less disabled patients achieved transient stabilization for 4, 16, and 35 months, indicating limited benefit for severely disabled PNS but potential for stabilization in less disabled cases.

Abstract

<h3>OBJECTIVES</h3> To evaluate the effect of a combination of immunoglobulins (IVIg), cyclophosphamide (CTX), and methylprednisolone (MP) on the clinical course of patients with paraneoplastic neurological syndrome (PNS) and antineuronal antibodies (Abs). <h3>METHODS</h3> Seventeen patients with paraneoplastic encephalomyelitis/sensory neuropathy (PEM/SN) with anti-Hu Abs (n=10) or cerebellar degeneration (PCD) with anti-Yo Abs (n=7) received one to nine cycles (mean 3.5) of a combination of IVIg (0.5 g/kg/day from days 1 to 5), CTX (600 mg/m2 at day 1) and MP (1g/day from day 1 to 3). The Rankin scale (RS) was used to evaluate the response. A positive response was considered as either improvement or stabilisation in patients who were still ambulatory (RS⩽3) at the onset of treatment, whereas only improvement, and not stabilisation, was considered a therapeutic benefit in bedridden patients (RS⩾4). <h3>RESULTS</h3> Tolerance was good and no patient experienced grade 3/4 toxicity (World Health Organisation). Sixteen patients were evaluable for response. Of the seven patients with RS⩾4, none improved. Of the nine patients with RS⩽3, none improved but three (two SN and one PCD) stabilised for 4, 35, and 16 months. <h3>CONCLUSIONS</h3> This study suggests that vigorous immunosuppressive treatment is not useful in severely disabled PNS patients with antineuronal Abs. In a minority of patients (mainly with SN) who are not severely disabled at the onset of treatment, a transient stabilisation is possible and deserves further evaluation.