Hyponatremia and other electrolyte abnormalities in patients receiving immune checkpoint inhibitors

Nephrology Dialysis Transplantation - Tập 36 Số 12 - Trang 2241-2247 - 2021
Harish Seethapathy1, Nifasha Rusibamayila1, Donald F. Chute1, Meghan Lee2, Ian A. Strohbehn2, Leyre Zubiri3, Alexander T. Faje4, Kerry L. Reynolds3, Kenar D. Jhaveri5, Meghan E. Sise1
1Department of Internal Medicine, Division of Nephrology, Massachusetts General Hospital, Boston, MA, USA
2Department of Internal Medicine, Gastrointestinal Unit, Massachusetts General Hospital, Boston, MA, USA
3Department of Internal Medicine, Division of Hematology and Oncology, Massachusetts General Hospital, Boston, MA, USA
4Department of Internal Medicine, Division of Endocrinology, Massachusetts General Hospital, Boston, MA, USA
5Division of Kidney Diseases and Hypertension, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA

Tóm tắt

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.

Từ khóa


Tài liệu tham khảo

Ribas, 2018, Cancer immunotherapy using checkpoint blockade, Science, 359, 1350, 10.1126/science.aar4060

Topalian, 2019, Five-year survival and correlates among patients with advanced melanoma, renal cell carcinoma, or non-small cell lung cancer treated with nivolumab, JAMA Oncol, 5, 1411, 10.1001/jamaoncol.2019.2187

Wolchok, 2015, PD-1 blockers, Cell, 162, 937, 10.1016/j.cell.2015.07.045

Marquart, 2018, Estimation of the percentage of US patients with cancer who benefit from genome-driven oncology, JAMA Oncol, 4, 1093, 10.1001/jamaoncol.2018.1660

Haslam, 2020, Estimation of the percentage of US patients with cancer who are eligible for immune checkpoint inhibitor drugs, JAMA Netw Open, 3, e200423, 10.1001/jamanetworkopen.2020.0423

Larkin, 2015, Combined nivolumab and ipilimumab or monotherapy in untreated melanoma, N Engl J Med, 373, 23, 10.1056/NEJMoa1504030

Postow, 2018, Immune-related adverse events associated with immune checkpoint blockade, N Engl J Med, 378, 158, 10.1056/NEJMra1703481

Seethapathy, 2019, The incidence, causes, and risk factors of acute kidney injury in patients receiving immune checkpoint inhibitors, Clin J Am Soc Nephrol, 14, 1692, 10.2215/CJN.00990119

Cortazar, 2020, Clinical features and outcomes of immune checkpoint inhibitor-associated AKI: a multicenter study, J Am Soc Nephrol, 31, 435, 10.1681/ASN.2019070676

Cortazar, 2016, Clinicopathological features of acute kidney injury associated with immune checkpoint inhibitors, Kidney Int, 90, 638, 10.1016/j.kint.2016.04.008

Tan, 2019, Spectrum of immune checkpoint inhibitors-induced endocrinopathies in cancer patients: a scoping review of case reports, Clin Diabetes Endocrinol, 5, 1, 10.1186/s40842-018-0073-4

Barroso-Sousa, 2018, Incidence of endocrine dysfunction following the use of different immune checkpoint inhibitor regimens: a systematic review and meta-analysis, JAMA Oncol, 4, 173, 10.1001/jamaoncol.2017.3064

Zhai, 2019, Endocrine toxicity of immune checkpoint inhibitors: a real-world study leveraging US food and drug administration adverse events reporting system, J Immunother Cancer, 7, 286, 10.1186/s40425-019-0754-2

Wanchoo, 2017, Adverse renal effects of immune checkpoint inhibitors: a narrative review, Am J Nephrol, 45, 160, 10.1159/000455014

Cantini, 2020, Electrolyte disorders in advanced non-small cell lung cancer patients treated with immune check-point inhibitors: a systematic review and meta-analysis, Crit Rev Oncol Hematol, 151, 102974, 10.1016/j.critrevonc.2020.102974

Manohar, 2019, Programmed cell death protein 1 inhibitor treatment is associated with acute kidney injury and hypocalcemia: meta-analysis, Nephrol Dial Transplant, 34, 108, 10.1093/ndt/gfy105

National Cancer Institute. Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Washington, DC: US Department of Health and Human Services,

Faje, 2019, Hypophysitis secondary to nivolumab and pembrolizumab is a clinical entity distinct from ipilimumab-associated hypophysitis, Eur J Endocrinol, 181, 211, 10.1530/EJE-19-0238

Osterlind, 1986, Prognostic factors in small cell lung cancer: multivariate model based on 778 patients treated with chemotherapy with or without irradiation, Cancer Res, 46, 4189

Rawson, 1990, An overview of prognostic factors in small cell lung cancer. A report from the Subcommittee for the Management of Lung Cancer of the United Kingdom Coordinating Committee on Cancer Research, Br J Cancer, 61, 597, 10.1038/bjc.1990.133

Waikar, 2009, Mortality after hospitalization with mild, moderate, and severe hyponatremia, Am J Med, 122, 857, 10.1016/j.amjmed.2009.01.027

Doshi, 2018, Prognostic significance of pretreatment sodium levels in patients of nonsmall cell lung cancer treated with pemetrexed-platinum doublet chemotherapy, J Can Res Ther, 14, 1049, 10.4103/0973-1482.187296

Boscoe, 2006, Cost of illness of hyponatremia in the United States, Cost Eff Resour Alloc, 4, 10, 10.1186/1478-7547-4-10

Rosner, 2014, Electrolyte disorders associated with cancer, Adv Chronic Kidney Dis, 21, 7, 10.1053/j.ackd.2013.05.005

Shirali, 2016, Electrolyte and Acid–Base Disorders in Malignancy

Li, 2020, Electrolyte and acid-base disorders in cancer patients and its impact on clinical outcomes: evidence from a real-world study in China, Ren Fail, 42, 234, 10.1080/0886022X.2020.1735417

Wang, 2017, Immune-related adverse events associated with anti-PD-1/PD-L1 treatment for malignancies: a meta-analysis, Front Pharmacol, 8, 730, 10.3389/fphar.2017.00730

Brahmer, 2010, Phase I study of single-agent anti-programmed death-1 (MDX-1106) in refractory solid tumors: safety, clinical activity, pharmacodynamics, and immunologic correlates, J Clin Oncol, 28, 3167, 10.1200/JCO.2009.26.7609

Thông tin
Thông tin xuất bản

Nephrology Dialysis Transplantation

Tập 36 Số 12

2241-2247

Thông tin tác giả