Rituximab Seen to Stop Myasthenia Gravis-like Symptoms Linked to Immune Therapies in Cancer Patient

Use of rituximab can reverse myasthenia gravis-like symptoms in cancer patients being treated with immune checkpoint inhibitors like Opdivo or Yervoy, a case study reports.

The study, “Rituximab as initial therapy for the reversal of myasthenia gravis neurotoxicity caused by ipilimumab/nivolumab” was published in the journal Neuro-Oncology and presented at the 23rd Annual Scientific Meeting and Education Day of the Society for Neuro-Oncology that recently took place in New Orleans, Louisiana.

Therapies for patients with melanoma, a type of skin cancer, often include Opdivo (nivolumab) or Yervoy (ipilimumab) alone or combined. Both therapies belong to the class of immune checkpoint inhibitors and work by enhancing the immune system’s response against tumor cells.

However, previous studies have reported a risk of a myasthenia gravis-like syndrome developing in melanoma patients treated with Opdivo and/or Yervoy.

Rituximab, a monoclonal antibody that targets the CD20 protein, is approved by the U.S. Food and Drug Administration (FDA) to treat non-Hodgkin’s lymphoma, chronic lymphocytic leukemia, rheumatoid arthritis, and granulomatosis with polyangiitis. Rituximab is marketed under the brand name Rituxan (Genentech) in the U.S. and MabThera (Roche) in Europe.

The antibody is also a mainstay in therapies for a broad variety of B-cell conditions, including myasthenia gravis. When bound to CD20, the antibody reduces the number of B-cells, slowing progression of myasthenia gravis and improving disease symptoms, reducing the need for other medications.

In this case study, researchers describe a 70-year old woman with melanoma participating in a clinical trial testing the effects of Opdivo versus the combination of Opdivo and Yervoy.

She developed double vision and intermittent drooping of the upper eyelid in both eyes shortly after the first treatment cycle.

Her eye symptoms worsened and the patient developed muscle weakness. One year later, she was diagnosed with myasthenia gravis.

Lung function was also declining, but the patient refused hospital admission. She began treatment with Mestinon (pyridostigmine), a common therapy for myasthenia gravis, with the immune suppressor prednisone (sold as Deltasone, among other names) but she failed to show improvement.

One dose of rituximab administered intravenously — directly into the bloodstream — at 375 mg/m2 led to improvements in her lung function, as shown by an increase of in forced vital capacity (the maximum amount of air a person can expel from the lungs after a maximum inhalation).

The patient was discharged with a prescription of prednisone and Mestinon. But, three days after being treated with rituximab, she no longer had symptoms.

“Our study shows the importance of Rituximab as initial therapy for the reversal of MG [myasthenia gravis] like syndrome caused by Ipilimumab/Nivolumab,” the researchers concluded.