John Cuenca, MD (he/him/his)
Clinical Research Assistant
The University of Texas MD Anderson Cancer Center
Houston, Texas
Disclosure information not submitted.
Jeannee Campbell, MPAS
Physician Assistant
The University of Texas MD Anderson Cancer Center, United States
Disclosure information not submitted.
Sudhakar Tummala, MD, MBA, CMQ, FACNS
Physician
The University of Texas MD Anderson Cancer Center, United States
Disclosure information not submitted.
Gregory Botz, MD, FCCM
Physician
The University of Texas MD Anderson Cancer Center, United States
Disclosure information not submitted.
Title: Respiratory Failure due to Pembrolizumab-induced Severe Diaphragmatic Myositis: A Case Report
Case Report Body:
Introduction: Pembrolizumab is a monoclonal antibody that activates tumor-specific cytotoxic T cells by targeting the programmed cell death-1 receptor(PD-1). Immune-related (IR) adverse events such as myositis can arise due to decreased immune self-tolerance. We report a case of hypercapnic respiratory failure from pembrolizumab-induced severe myositis.
Description: A 61-year old female with a past medical history of hypertension, morbid obesity, and metastatic clear cell renal carcinoma presented to the hospital with shortness of breath, headache, and myalgia. She had received the first cycle of pembrolizumab/axitinib 2 weeks prior. She was admitted to the ICU due to malignant hypertension and acute hypercapnic respiratory failure (PaO2=64mmHg; pH=7.26; PaCO2=70mmHg). Due to elevation of CK (5,525 U/L), troponin T (651 ng/L), and a negative coronary angiography, IR myocarditis and myositis were diagnosed and treated with high-dose steroids. To treat potential myasthenia gravis(MG), she underwent plasmapheresis and low-dose pyridostigmine. The antibody assay found positive ACHr, negative MuSK, and positive striated muscle IgG autoantibodies. Nevertheless, MG treatment was stopped after the EMG showed no evidence of neuromuscular junction dysfunction, along with findings suggestive of myositis with muscle membrane instability. As the hypoventilation continued, additional immunosuppression with rituximab, infliximab, and abatacept was given. The respiratory failure worsened over the next 2 weeks, and the patient required invasive mechanical ventilation. A follow-up EMG showed absent bilateral phrenic nerve responses. In addition, an ultrasound image showed a markedly thin diaphragm. Efforts to wean the patient from the ventilator were unsuccessful. Hence, the decision to perform a tracheostomy and gastrostomy was made. After being admitted for 7 weeks, despite a relative improvement, the patient still required respiratory support and was discharged to a long-term facility.
Discussion: Severe myositis is a rare IR-toxicity of the checkpoint inhibitors that, if left untreated, can be fatal. As checkpoint inhibitors become more widely used, clinicians caring for critically ill cancer patients in the community should be aware of this unusual IR adverse event to allow for a prompt diagnostic workup and early management.