Harish Seethapathy1, Nifasha Rusibamayila1, Donald F Chute1, Meghan Lee2, Ian Strohbehn2, Leyre Zubiri3, Alexander T Faje4, Kerry L Reynolds3, Kenar D Jhaveri5, Meghan E Sise1. 1. Department of Internal Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA. 2. Department of Internal Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA. 3. Department of Internal Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA. 4. Department of Internal Medicine, Division of Endocrinology, Massachusetts General Hospital, Boston, MA, USA. 5. Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA.
Abstract
BACKGROUND: Hyponatremia due to endocrinopathies such as adrenal insufficiency and hypothyroidism has been reported in patients receiving immune checkpoint inhibitors (ICIs). We determined the risk and predictors of hyponatremia and other electrolyte abnormalities in a 'real-world' sample of patients receiving ICIs to treat advanced malignancies. METHODS: This was a retrospective observational study of all patients who received ICIs from a single cancer center between 2011 and 2018. Patients were followed for 12 months after initiation of ICIs or until death. Common Terminology for Cancer Adverse Events version 5.0 criteria were used to grade the severity of hyponatremia and other electrolyte abnormalities. The predictors of severe (Grade 3 or 4) hyponatremia were determined using a multivariable logistic regression model. The etiology of Grade 3 or 4 hyponatremia was determined by chart review. RESULTS: A total of 2458 patients were included. Their average age was 64 years [standard deviation (SD) 13], 58% were male and 90% were white. In the first year after starting ICIs, 62% experienced hyponatremia (sodium <134 mEq/L) and 136 (6%) experienced severe hyponatremia (<124 mEq/L). Severe hyponatremia occurred on average 164 days (SD 100) after drug initiation. Only nine cases of severe hyponatremia were due to endocrinopathies (0.3% overall incidence). Risk factors for severe hyponatremia included ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor) use, diuretic use and non-White race. Other severe electrolyte abnormalities were also commonly observed: severe hypokalemia (potassium <3.0 mEq/L) occurred in 6%, severe hyperkalemia (potassium ≥6.1 mEq/L) occurred in 0.6%, severe hypophosphatemia (phosphorus <2 mg/dL) occurred in 17% and severe hypocalcemia (corrected calcium <7.0 mg/dL) occurred in 0.2%. CONCLUSIONS: Hyponatremia is common in cancer patients receiving ICIs. However, endocrinopathies are an uncommon cause of severe hyponatremia.
BACKGROUND: Hyponatremia due to endocrinopathies such as adrenal insufficiency and hypothyroidism has been reported in patients receiving immune checkpoint inhibitors (ICIs). We determined the risk and predictors of hyponatremia and other electrolyte abnormalities in a 'real-world' sample of patients receiving ICIs to treat advanced malignancies. METHODS: This was a retrospective observational study of all patients who received ICIs from a single cancer center between 2011 and 2018. Patients were followed for 12 months after initiation of ICIs or until death. Common Terminology for Cancer Adverse Events version 5.0 criteria were used to grade the severity of hyponatremia and other electrolyte abnormalities. The predictors of severe (Grade 3 or 4) hyponatremia were determined using a multivariable logistic regression model. The etiology of Grade 3 or 4 hyponatremia was determined by chart review. RESULTS: A total of 2458 patients were included. Their average age was 64 years [standard deviation (SD) 13], 58% were male and 90% were white. In the first year after starting ICIs, 62% experienced hyponatremia (sodium <134 mEq/L) and 136 (6%) experienced severe hyponatremia (<124 mEq/L). Severe hyponatremia occurred on average 164 days (SD 100) after drug initiation. Only nine cases of severe hyponatremia were due to endocrinopathies (0.3% overall incidence). Risk factors for severe hyponatremia included ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor) use, diuretic use and non-White race. Other severe electrolyte abnormalities were also commonly observed: severe hypokalemia (potassium <3.0 mEq/L) occurred in 6%, severe hyperkalemia (potassium ≥6.1 mEq/L) occurred in 0.6%, severe hypophosphatemia (phosphorus <2 mg/dL) occurred in 17% and severe hypocalcemia (corrected calcium <7.0 mg/dL) occurred in 0.2%. CONCLUSIONS: Hyponatremia is common in cancer patients receiving ICIs. However, endocrinopathies are an uncommon cause of severe hyponatremia.
Authors: Harish Seethapathy; Sophia Zhao; Donald F Chute; Leyre Zubiri; Yaa Oppong; Ian Strohbehn; Frank B Cortazar; David E Leaf; Meghan J Mooradian; Alexandra-Chloé Villani; Ryan J Sullivan; Kerry Reynolds; Meghan E Sise Journal: Clin J Am Soc Nephrol Date: 2019-10-31 Impact factor: 8.237
Authors: Meng H Tan; Ravi Iyengar; Kara Mizokami-Stout; Sarah Yentz; Mark P MacEachern; Li Yan Shen; Bruce Redman; Roma Gianchandani Journal: Clin Diabetes Endocrinol Date: 2019-01-22
Authors: Suzanne L Topalian; F Stephen Hodi; Julie R Brahmer; Scott N Gettinger; David C Smith; David F McDermott; John D Powderly; Jeffrey A Sosman; Michael B Atkins; Philip D Leming; David R Spigel; Scott J Antonia; Alexander Drilon; Jedd D Wolchok; Richard D Carvajal; M Brent McHenry; Fareeda Hosein; Christopher T Harbison; Joseph F Grosso; Mario Sznol Journal: JAMA Oncol Date: 2019-10-01 Impact factor: 31.777
Authors: Romualdo Barroso-Sousa; William T Barry; Ana C Garrido-Castro; F Stephen Hodi; Le Min; Ian E Krop; Sara M Tolaney Journal: JAMA Oncol Date: 2018-02-01 Impact factor: 31.777