Adverse Effects of Immune Checkpoint Therapy in Cancer Patients Visiting the Emergency Department of a Comprehensive Cancer Center.

STUDY OBJECTIVE: Cancer immunotherapy is evolving rapidly and is transforming cancer care. During the last decade, immune checkpoint therapies have been developed to enhance the immune response; however, specific adverse effects related to autoimmunity are increasingly apparent. This study aims to fill the knowledge gap related to the spectrum of immune-related adverse effects among cancer patients visiting emergency departments (EDs). METHODS: We performed a retrospective review of patients treated with immune checkpoint therapy who visited the ED of a comprehensive cancer center between March 1, 2011, and February 29, 2016. Immune-related adverse effects from the ED visits were identified and profiled. We analyzed the association of each immune-related adverse effect with overall survival from the ED visit to death. RESULTS: We identified 1,026 visits for 628 unique patients; of these, 257 visits (25.0%) were related to one or more immune-related adverse effects. Diarrhea was the most common one leading to an ED visit. The proportions of ED visits associated with diarrhea, hypophysitis, thyroiditis, pancreatitis, or hepatitis varied significantly by immune checkpoint therapy agent. Colitis was significantly associated with better prognosis, whereas pneumonitis was significantly associated with worse survival. CONCLUSION: Cancer patients treated with ipilimumab, nivolumab, or pembrolizumab may have a spectrum of immune-related adverse effects that require emergency care. Future studies will need to update this profile as further novel immunotherapeutic agents are added.

Cocaine and Opioid-Induced Acute Liver Injury: A Rare Case Report.

Drug overdose has been a public health burden in the United States. Repeated use of cocaine and heroin may increase the risk of severe acute liver failure. We present the case of a middle-aged man with no significant past medical condition except a chronic history of drug abuse who presented to our hospital after an overdose of cocaine and heroin. Patient received Narcan by paramedics and continued treatment in the emergency room (ER). Patient has exhibited multiple organ failures, such as acute liver failure, rhabdomyolysis, acute kidney injury, and acute respiratory hypoxic hypercapnic respiratory failure likely due to respiratory center depression. The patient was placed on a non-rebreather mask then a bilevel positive airway pressure (BiPAP) machine. Patient failed the BiPAP trial, was intubated and later extubated after five days, and discharged on room air. The patient was admitted to the intensive care unit due to toxic encephalopathy. Liver enzymes were markedly elevated during admission and trended down after supportive management, Narcan, and N-acetylcysteine treatment.

Acalabrutinib-related second primary malignancies and nonmelanoma skin cancers in patients with chronic lymphocytic leukaemia (CLL): A systematic review and meta-analysis of randomised controlled trials (RCTs).

Acalabrutinib is a second generation Bruton's tyrosine kinase inhibitor and was recently approved in the treatment of chronic lymphocytic leukaemia. We undertook a systematic review and meta-analysis of randomised controlled trials to determine the risks of acalabrutinib-related second primary malignancies (SPM) and nonmelanoma skin cancers (NMSC). The incidence of SPM was 4.7% higher in the acalabrutinib arm compared to control arm with risk ratio (RR) of 1.76 (5.32 vs 3.2 per 100 person-years). Notably, NMSC was the most common SPM, and the incidence was 2.56 per 100 person-years in the acalabrutinib group versus 1.12 per 100 person-years in the control group (RR 2.43). Long-term follow-up and future studies are necessary to define the actual relationship and their risk factors.