Clinical characteristics, treatment and outcome of nivolumab-induced myasthenia gravis

Invest New Drugs. 2023 Apr;41(2):333-339. doi: 10.1007/s10637-023-01347-6. Epub 2023 Mar 29.

Abstract

Background: To investigate the clinical features of nivolumab-induced myasthenia gravis (MG) and provide evidence for the rational use of nivolumab in the clinic.

Methods: We collected case reports and case series of nivolumab-induced MG for retrospective analysis by searching Chinese and English databases from 2014 to October 31, 2022.

Results: Of the 67 patients included, the median age was 72.5 years (range 34-86), including 44 males (65.7%). MG occurred in the median 2nd treatment cycle (range, 1st-6th) after nivolumab treatment, being mild in 12 patients (17.9%) and moderate to severe in 44 patients (65.7%). Ptosis (n = 48,71.6%), diplopia (n = 34,50.7%), dyspnea (n = 30, 44.8%), limb muscle weakness (n = 30, 44.8%) and dysphagia (n = 27, 40.3%) were the most common symptoms. Fifty-six patients (83.6%) were classified as having generalized myasthenia gravis (GMG), the remaining 11 patients (16.4%) isolated ocular myasthenia gravis (OMG). Twenty-one patients (31.3%) had MG combined with myositis, 10 patients (14.9%) had myocarditis, and 9 patients (13.4%) had both myositis and myocarditis. Forty patients (59.7%) were positive for anti-acetylcholine receptor antibodies. The serum creatine kinase level was significantly increased in 37 patients (55.2%), with a median value of 4000 IU/L (219,14229). After discontinuation of nivolumab and immunosuppressive therapy, 46 patients (68.7%) finally recovered or improved their MG symptoms, while 15 patients (22.4%) did not recover. Eleven patients (16.4%) died of MG complications.

Conclusion: MG is a serious and rare adverse reaction to nivolumab. Nivolumab-induced MG should be timely and correctly identified, and immunotherapy should be given.

Keywords: Immune checkpoint inhibitors; Myasthenia gravis; Nivolumab; PD-1 inhibitor; Ptosis.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Humans
  • Male
  • Middle Aged
  • Myasthenia Gravis* / chemically induced
  • Myasthenia Gravis* / complications
  • Myasthenia Gravis* / drug therapy
  • Myocarditis* / chemically induced
  • Myocarditis* / complications
  • Myocarditis* / drug therapy
  • Myositis* / chemically induced
  • Myositis* / diagnosis
  • Myositis* / drug therapy
  • Nivolumab / adverse effects
  • Retrospective Studies
  • Treatment Outcome

Substances

  • Nivolumab