Waleed Qaddumi, BS
Medical Student
The George Washington University, United States
Disclosure information not submitted.
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.
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: Hypophysitis and Pneumonitis Secondary to Checkpoint Inhibitor Combination Therapy: A Case Report
Case Report Body:
Introduction: Tumor cells evade immunosurveillance through various means, such as targeting the CTLA-4 and PD-1 pathways. Immune checkpoint inhibitors (ICIs) inhibit these pathways, thus promoting T cell proliferation and cytotoxicity. Although ICIs show promising benefits, immune-related adverse events (IRAE) have been reported. We present a case of ICI pneumonitis and hypophysitis.
Description: A 30-year-old male with acute myelogenous leukemia, currently on nivolumab/ipilimumab, presents to the ED with acute shortness of breath. On presentation, he had hypoxic respiratory failure, tachycardia, fever, and bilateral infiltrates. He required high flow oxygen therapy (HFOT) and was transferred to the ICU with suspected ICI pneumonitis. He was started on broad-spectrum antimicrobials, high-dose steroids, and infliximab. The patient’s respiratory status continued to worsen and required intubation. After ruling out other etiologies, ICI pneumonitis was diagnosed. Review of systems showed polydipsia and polyuria of 10L per day, serum Osm (326 mOsm/Kg) and urine Osm (111 mOsm/Kg) were consistent with ICI-related DI and was started on DDVAP. Hypernatremia continued to worsen, suggesting a partial nephrogenic DI. Additionally, a cosyntropin stimulation test indicated central adrenal insufficiency. Therefore, ICI hypophysitis was diagnosed. After 21 days in the ICU, he was extubated to HFOT, thus was moved to the floor. His hospital course was complicated by severe Pneumocystis jiroveci pneumonia and hepatitis. Hepatitis was due to a mixed injury of autoimmune ICI-related and hepatotoxic liver injury due to infliximab; and was managed with steroids, IVIG, and mycophenolate. After 83 days on the floor, he was weaned to room air, had improved muscular strength, recovered hepatic function, and was discharged. Unfortunately, he was readmitted after one week with fever and tachypnea. He continued to regress and passed away 3 months later from respiratory complications.
Conclusion: The applications of ICI therapies are pivotal in managing advanced cancers. ICU staff should be aware that although revolutionary, ICIs are associated with potentially life-threatening IRAEs. Similar to this patient, a multidisciplinary approach is necessary.