Adverse Effects of Immune Checkpoint Inhibitors (Programmed Death-1 Inhibitors and Cytotoxic T-Lymphocyte-Associated Protein-4 Inhibitors): Results of a Retrospective Study

TY - JOUR

T1 - Adverse Effects of Immune Checkpoint Inhibitors (Programmed Death-1 Inhibitors and Cytotoxic T-Lymphocyte-Associated Protein-4 Inhibitors)

T2 - Results of a Retrospective Study

AU - Bajwa, Ravneet

AU - Cheema, Anmol

AU - Khan, Taimoor

AU - Amirpour, Alireza

AU - Paul, Anju

AU - Chaughtai, Saira

AU - Patel, Shrinil

AU - Patel, Tejas

AU - Bramson, Joshua

AU - Gupta, Varsha

AU - Levitt, Michael

AU - Asif, Arif

AU - Hossain, Mohammad A.

N1 - Publisher Copyright: © The authors | Journal compilation

PY - 2019

Y1 - 2019

N2 - In recent years the use of immunomodulating therapy to treat various cancers has been on the rise. Three checkpoint inhibitors have been approved by the Food and Drug Administration (ipilimumab, pembrolizumab and nivolumab). The use of these drugs comes with serious adverse events related to excessive immune activation, collectively known as immune-related adverse events (irAEs). We conducted a system-based review of 139 case reports/case series that have described these adverse events between January 2016 and April 2018, found in the PubMed database. There was a broad spectrum of presentations, doses and checkpoint inhibitors used. The most common check point inhibitor observed in our literature review was nivolumab. The most common adverse effects encountered were colitis (14/139), hepatitis (11/139), adrenocorticotropic hormone insufficiency (12/139), hypothyroidism (7/139), type 1 diabetes (22/139), acute kidney injury (16/139) and myocarditis (10/139). The treatment most commonly consisted of cessation of the immune checkpoint inhibitor, initiation of steroids and supportive therapy. This approach provided a complete resolution in a majority of cases; however, there were many that developed long-term adverse events with deaths reported in a few cases. The endocrine system was the mostly commonly affected with the development of type 1 diabetes mellitus or diabetic ketoacidosis being the most frequently reported adverse events. While immunomodulating therapy is a significant advance in the management of various malignancies, it is capable of serious adverse effects.

AB - In recent years the use of immunomodulating therapy to treat various cancers has been on the rise. Three checkpoint inhibitors have been approved by the Food and Drug Administration (ipilimumab, pembrolizumab and nivolumab). The use of these drugs comes with serious adverse events related to excessive immune activation, collectively known as immune-related adverse events (irAEs). We conducted a system-based review of 139 case reports/case series that have described these adverse events between January 2016 and April 2018, found in the PubMed database. There was a broad spectrum of presentations, doses and checkpoint inhibitors used. The most common check point inhibitor observed in our literature review was nivolumab. The most common adverse effects encountered were colitis (14/139), hepatitis (11/139), adrenocorticotropic hormone insufficiency (12/139), hypothyroidism (7/139), type 1 diabetes (22/139), acute kidney injury (16/139) and myocarditis (10/139). The treatment most commonly consisted of cessation of the immune checkpoint inhibitor, initiation of steroids and supportive therapy. This approach provided a complete resolution in a majority of cases; however, there were many that developed long-term adverse events with deaths reported in a few cases. The endocrine system was the mostly commonly affected with the development of type 1 diabetes mellitus or diabetic ketoacidosis being the most frequently reported adverse events. While immunomodulating therapy is a significant advance in the management of various malignancies, it is capable of serious adverse effects.

KW - Immunomodulating therapy

KW - Immunotherapy side effects

KW - Ipilimumab

KW - Nivolumab

KW - Pembrolizumab

KW - Programmed cell death inhibitors

UR - https://www.scopus.com/pages/publications/85074415705

U2 - 10.14740/jocmr3750

DO - 10.14740/jocmr3750

M3 - Review article

SN - 1918-3003

VL - 11

SP - 225

EP - 236

JO - Journal of Clinical Medicine Research

JF - Journal of Clinical Medicine Research

IS - 4

ER -