John Cuenca, MD (he/him/his)
Clinical Research Assistant
The University of Texas MD Anderson Cancer Center
Houston, Texas
Disclosure information not submitted.
Robert Wegner, MD, FASA
Assistant Professor
The University of Texas MD Anderson Cancer Center, United States
Disclosure information not submitted.
Joshua Botdorf, DO
Assistant Professor
University of Texas MD Anderson Cancer Center, Texas, United States
Disclosure information not submitted.
Cezar Iliescu, MD, FACC, FSCAI
Professor
The University of Texas MD Anderson Cancer Center, United States
Disclosure information not submitted.
Joseph Nates, MBA, MD
Professor, Deputy Chair, Director ICUs
University of Texas MD Anderson Center
Bellaire, Texas, United States
Disclosure information not submitted.
Dereddi Raja Reddy, MD, FACP FCCP
Assistant Professor, Program Director MS4 McGovern Medical School
MD Anderson Cancer Care Center
Houston, Texas
Disclosure information not submitted.
Title: Immune Checkpoint Inhibitors-induced Overlap Syndrome: A Case Series
INTRODUCTION/HYPOTHESIS: Immune checkpoints inhibitors (ICI) are essential for current oncology therapy. However, ICI can be associated with life-threatening immune-related adverse events (IRAEs). The overlap syndrome is a combination of ICI-induced myocarditis, myositis, or myasthenia gravis (MG).
Methods: A case series of 3 critically ill cancer patients with overlap syndrome. All 3 patients had normal wall motion on echocardiogram and no obstructive coronary artery disease on the heart catheterization.
Results: Case 1. A 62-year-old male with metastatic renal clear cell carcinoma treated with nivolumab/ipilimumab presented to the EC with acute respiratory failure and weakness. He had high troponin T (620), CK (499), and CKMB (61.2). EKG showed sinus tachycardia without ischemic changes. He was admitted to the ICU for suspected ICI-related overlap syndrome. Pulse-dose steroids and plasmapheresis (PLEX) were started. Due to lack of improvement, additional immunosuppression with rituximab was started. Myocardial and quadriceps biopsies showed leukocyte infiltration confirming myocarditis and myositis. After clinical improvement, he was transferred to the floor. Case 2. A 76-year-old male with metastatic prostate cancer managed with nivolumab/ipilimumab presented with dyspnea, weakness, and dysphagia. Due to his high troponin T (826) and CK (2206), he was admitted to the ICU for concerns of overlap syndrome. Steroids and PLEX were started. EMG suggested axonal and demyelinating motor and sensory peripheral neuropathy. Biopsies confirmed myocarditis and myositis. Case 3. A 72-year-old male with metastatic squamous cell carcinoma of the groin presented to the EC, after his 3rd cycle of cemiplimab, with worsening muscle weakness and dysphagia. Laboratory confirmed overlap syndrome. Despite pulse-dose steroids and PLEX, the troponins remained high. Additional treatment with IVIG, rituximab, and pyridostigmine was given. Cardiac biopsy was consistent with myocarditis. The patient couldn't be weaned off the ventilator due to poor respiratory mechanics and was discharged to a long-term facility.
Conclusion: The incidence of rare and potentially fatal IRAE toxicities is increasing with the growing use and indications of ICI therapy. ICU staff managing cancer patients should be aware of the IRAEs and their management.