Multiple Sclerosis and other Neurological Conditions
Albert J. Thayil, DO
Resident Physician, PGY-4
Macon & Joan Brock Virginia Health Sciences Eastern Virginia Medical School at Old Dominion University
Norfolk, Virginia, United States
Naga R. Ganti, BS
Medical Student, MS-2
Macon & Joan Brock Virginia Health Sciences Eastern Virginia Medical School at Old Dominion University
Manalapan Township, New Jersey, United States
Karen Luna, MD
Resident Physician, PGY-3
Macon & Joan Brock Virginia Health Sciences Eastern Virginia Medical School at Old Dominion University
-, Virginia, United States
Nataly Montes-Chinea, MD
Attending Physician
Macon & Joan Brock Virginia Health Sciences Eastern Virginia Medical School at Old Dominion University
Norfolk, Virginia, United States
Kevin Ha, MD, PhD
Attending Physician
Macon & Joan Brock Virginia Health Sciences Eastern Virginia Medical School at Old Dominion University
-, Virginia, United States
Jim Wyant, MD
Attending Physician
Macon & Joan Brock Virginia Health Sciences Eastern Virginia Medical School at Old Dominion University
-, Virginia, United States
Albert J. Thayil
Edward Via College of Osteopathic Medicine - Carolinas Campus
Indian Land, South Carolina, United States
Nivolumab is an immune checkpoint inhibitor that uses monoclonal antibodies to target programmed cell death protein 1 (PD-1) to augment T-cell activation against tumor cells. Even though this agent has improved survival rates of cancer patients, it can also lead to autoimmune Triple M syndrome, consisting of myasthenia gravis, myocarditis, and myositis. Here we present a patient with nivolumab-induced Triple M syndrome:
A 63-year-old male with T3 N0 esophageal adenocarcinoma status-post esophagectomy, who, 26 days after receiving his first dose of nivolumab, presented with proximal muscle weakness, difficulty ambulating, dyspnea with activity, dysphagia, and chest pain. Nivolumab therapy was discontinued after the patient was found to have myocarditis. Further workup revealed positive acetylcholine receptor (AChR) antibodies and necrotizing myopathy with inflammation on the muscle biopsy. He required J-tube placement and intubation despite pyridostigmine, steroids, plasmapheresis, and intravenous immunoglobulin. During subsequent acute rehabilitation, he developed bacteremia while on ventilatory support.
Discussions:
Methotrexate therapy was offered for his neuromuscular symptoms; however, the patient declined therapy due to the risks involved with his active infection. After 54 days, he was transferred to a skilled nursing facility for continued rehabilitation and ventilatory weaning. After 3 months, he improved clinically and was transitioned to outpatient therapy. This patient had Triple M syndrome from one dose of nivolumab. Prognosis is often poor, even when the agent is discontinued and immunotherapy is added, which is why early identification is crucial in these cases. Although withdrawing immune checkpoint inhibitors may seem optimal, this can correspond with cancer progression.
Conclusions:
Shared decision-making among patients, oncologists, neurologists, and physiatrists is highly recommended when considering immune checkpoint inhibitors, which have potential neurologic adverse drug effects. A multidisciplinary approach is also required for managing its long-term complications.
