Rituximab for Immune Checkpoint Inhibitor Myasthenia Gravis

Abstract

The use of immune checkpoint inhibitors (iCPI) in the treatment of multiple cancers has gained prominence due to their high efficacy. However, neurological immune-related adverse events (irAEs) such as myasthenia gravis (MG) have been associated with iCPI therapy. Most of these neurological irAEs are rare, and in many cases, their diagnoses and management can be challenging.We present a case of a 70-year-old woman with stage IIIC melanoma who developed a new onset of gradually progressive dyspnea, diplopia, and bilateral ptosis following treatment with one cycle of nivolumab and ipilimumab (Nivo+Ipi). She was diagnosed with MG via positive serum acetylcholine receptor (AChR) antibodies. She had developed a severe dyspnea at rest, which was refractory to multiple immunesuppressive therapies including prednisone, pyridostigmine, and intravenous immunoglobulin (IVIG). Subsequently, she was treated with rituximab 375 mg/m 2 monthly every four weeks with significant improvement of her symptoms within 48 hours each time.As the implementation of immunotherapy increases in medical practice, irAEs may become more apparent. When first-line therapies are not adequate, other alternative therapies should be explored. This case of MG as an irAE shows that rituximab can provide a potential benefit to treating patients with immunotherapy-induced MG who are refractory to other standard treatments. Prospective studies are needed to further evaluate the efficacy of rituximab in the management of irAEs.

Immune-related adverse events of immune checkpoint inhibitors: a review

“…Rituximab has therapeutic effects on steroids- and immunoglobulin-refractory neuro-related adverse events induced by ICIs. The clinical symptoms and nerve conduction of patients with multiple neurological diseases ( 129 , 130 ) were significantly improved, and another patient with ICI induced myasthenia gravis ( 131 ) also benefited after rituximab treatment. In addition to the benefits of irAEs in the nervous system, rituximab also has an inhibitory effect on the reactivation of primary membranous nephropathy ( 132 ) related to ICIs, ensuring stable renal function and sustained ICI anti-tumor efficacy.…”

Current landscape and tailored management of immune-related adverse events

“…Since several irAEs were caused directly by autoantibodies, such as some hematological or neuromuscular irAEs, plasma exchange could be a feasible strategy against irAEs by removing the pathogenetic autoantibody from the circulation, especially in severe cases of myasthenia gravis or Guillain–Barré syndrome ( Touat et al, 2017 ). For instance, Verma et al showed that rituximab (targeted CD20) could be used to treat patients with immunotherapy-induced myasthenia gravis ( Verma et al, 2021 ). Clinical trials evaluating strategies to prevent irAEs are needed to institute in the future.…”

Immune checkpoint inhibitors induced side effects of the peripheral nervous system

“…classic form [21][22][23]. The value of recently licenced biologicals for the treatment of irMG like terminal complement inhibitors or neonatal Fc-receptor antagonists (FcRn) remains to be determined and has currently to be considered as an experimental therapy [14].…”

“…In severe and rapidly progressive cases, intravenous immunoglobulin (IVIG) or plasma exchange (PE) should be considered to decrease not only autoantibody load but also neutralize circulating ICIs [20]. In refractory cases, rituximab as an anti-CD20 B-cell depleting therapeutic antibody may also play a role like in the classic form [21–23]. The value of recently licenced biologicals for the treatment of irMG like terminal complement inhibitors or neonatal Fc-receptor antagonists (FcRn) remains to be determined and has currently to be considered as an experimental therapy [14].…”