Immune-Related Adverse Events in the Older Adult with Cancer Receiving Immune Checkpoint Inhibitor Therapy.

OBJECTIVE: Older adults with cancer (OAC) may be at elevated risk for immune-related adverse events (irAEs) during immune checkpoint inhibitor (ICI) therapy due to the normal organ function changes of aging, as well as related to a higher prevalence of comorbid conditions compared to younger patients. The importance of high-quality nursing care cannot be overstated for this population, including proactive symptom assessment, management, and coordination of care. The purpose of this paper is to describe the unique challenges faced by OAC receiving ICI drugs. METHODS: We present both a case study and the results of a single-institution retrospective study from a large, urban US National Cancer Institute- designated comprehensive cancer center. The retrospective study examined the frequency and intensity of irAEs experienced by patients aged 75 years or older who received ICI therapy between January 2016 and December 2018 for melanoma. RESULTS: We reviewed the records of 38 OAC (age range 75-92 years) with locally advanced or metastatic melanoma who received pembrolizumab, nivolumab and/or ipilimumab. Median length of therapy was 7.4 months, and median time to onset of irAEs was 81 days. Approximately half (47%) of the patients experienced Grade 1-3 irAEs, and discontinued therapy related to inability to tolerate the ICI more frequently than was reported in clinical trials (24%). CONCLUSIONS: OAC who receive ICI therapy frequently experience irAEs that may result in treatment interruption, discontinuation or long-lasting toxicity. Nurses are well positioned to provide support to this vulnerable population.

Clinical implications of drug-induced liver injury in early-phase oncology clinical trials.

BACKGROUND: Data on drug-induced liver injury (DILI) and acute liver failure (ALF) in modern phase 1 oncology trials are limited, specifically with respect to the incidence and resolution of DILI and the safety of drug rechallenge. METHODS: This study reviewed all patients who were recruited to phase 1 oncology trials between 2013 and 2017 at Memorial Sloan Kettering Cancer Center. Clinicopathologic data were extracted to characterize DILI, and attribution was assessed on the basis of data prospectively generated during the studies. Logistic regression models were used to explore factors related to DILI and DILI recurrence after drug rechallenge. RESULTS: Among 1670 cases recruited to 85 phase 1 trials, 81 (4.9%) developed DILI. The rate of DILI occurrence was similar for patients in immune-based trials and patients in targeted therapy trials (5.0% vs 4.9%), as was the median time to DILI (5.5 vs 6.5 weeks; P = .48). Two patients (0.12%) met the criteria of Hy's law, although none developed ALF. The DILI resolved in 96% of the patients. Pretreatment factors were not predictive for DILI development. Thirty-six of the 81 patients underwent a drug rechallenge, and 28% of these patients developed DILI recurrence. Peak alanine aminotransferase during the initial DILI was associated with DILI recurrence (odds ratio, 1.04; 95% confidence interval, 1.0-1.09; P = .035). CONCLUSIONS: In modern phase 1 oncology trials, DILI is uncommon, may occur at any time, and often resolves with supportive measures. Rechallenging after DILI is feasible; however, the high rate of DILI recurrence suggests that clinicians should consider the severity of the DILI episode and treatment alternatives.

Immune Checkpoint Inhibitors in Lung Cancer and Melanoma.

OBJECTIVE: To provide a synopsis of immune checkpoint inhibition in solid tumors with a focus on lung cancer and melanoma for the oncology nurse. DATA SOURCES: A literature search was conducted from 2012 to the present using key search terms including: ipilimumab, pembrolizumab, nivolumab, durvalumab, atezolizumab, immune checkpoint inhibitor, NSCLC or SCLC, melanoma, incidence, toxicity, and immune-related adverse events (irAEs). CONCLUSION: Immune checkpoint inhibition has caused a pivotal shift in the treatment of melanoma and lung cancer. Additionally, it has supported the use of immunotherapy as a modality and pillar of cancer treatment. The interdisciplinary team plays an integral role in facilitating patients' understanding of their treatment modality, symptom management, and guidance through their cancer journey. As more research continues in various tumor types to understand how immune-modulated agents can impact tumor burden, disease control, and quality of life, it is hoped that more patients will have access to these therapies. IMPLICATIONS FOR NURSING PRACTICE: Patient safety is paramount and nurses are aligned to educate, assess, and guide patients during immune checkpoint inhibitor therapy. Developing a rapport and relationship that is based on trust and open communication are vital for helping patients adhere to therapy and safely navigate symptom reporting at the onset of symptoms.

Immune Checkpoint Inhibitors: An Innovation in Immunotherapy for the Treatment and Management of Patients with Cancer.

Cancer survival rates are generally increasing in the United States. These trends have been partially attributed to improvement in therapeutic strategies. Cancer immunotherapy is an example of one of the newer strategies used to fight cancer, which primes or activates the immune system to produce antitumor effects. The first half of this review paper concisely describes the cell mechanisms that control antitumor immunity and the major immunotherapeutic strategies developed to target these mechanisms. The second half of the review discusses in greater depth immune checkpoint inhibitors that have recently demonstrated tremendous promise for the treatment of diverse solid tumor types, including melanoma, non-small cell lung cancer, and others. More specifically, the mechanisms of action, side effects, and patient and family management and education concerns are discussed to provide oncology nurses up-to-date information relevant to caring for cancer-affected patients treated with immune checkpoint inhibitors. Future directions for cancer immunotherapy are considered.

Checkpoint Inhibitors: Common Immune-Related Adverse Events and Their Management
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BACKGROUND: Immunotherapy, specifically the use of checkpoint inhibitors, offers patients with cancer an alternative to chemotherapy, targeting different pathways to destroy cancer cells. The side effects of immunotherapies, as well as their impact on normal tissue, need to be assessed and managed based on their mechanisms of action. OBJECTIVES: This article presents an overview of immune-related adverse events (AEs). 
. METHODS: Common immune-related toxicities, as well as rare and refractory toxicities, are reviewed. 
. FINDINGS: Immunotherapy treatment is an option for many patients with cancer, and nurses must understand the distinct side effect profile of these agents. Prompt identification and expert management are the cornerstones of success when dealing with immune-related AEs, and oncology nurses play a key role in improving patient care.

Understanding and Managing Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitors in Patients With Advanced Melanoma.

The immune checkpoint inhibitors ipilimumab, nivolumab, and pembrolizumab represent a substantial improvement in treating advanced melanoma but are associated with adverse events (AEs) likely related to general immunologic enhancement. To ensure that patients receive optimal benefit from these agents, prompt assessment and treatment of AEs are essential. We review the efficacy and safety profiles of these immune checkpoint inhibitors and describe guidelines for managing immune-related AEs. We also present case studies describing the management of toxicities in patients receiving immune checkpoint inhibitor therapy. These cases illustrate the importance of collecting a detailed medical history when administering immunotherapy, as this information is necessary to establish baseline, inform monitoring, and determine the etiology of symptoms. Advanced practice nurses and physician assistants are uniquely positioned to educate patients on the early recognition of AEs and have an important role in establishing appropriate monitoring and open dialogue among services.