Optimal management of immune-related toxicities associated with checkpoint inhibitors in lung cancer

Howell, Mary; Lee, Rebecca; Bowyer, Samantha; Fusi, Alberto; Lorigan, Paul

doi:10.1016/j.lungcan.2015.02.007

Cited by 44 publications

(41 citation statements)

References 49 publications

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“…Early T cell diversification after checkpoint inhibitors may therefore prove useful as an indicator of patients at risk for later IRAE development, and could serve as a new adjunct to current clinical management algorithms for IRAEs, which rely upon early recognition and intervention (17). This is especially pertinent as CTLA-4 blockade is being combined with anti-PD1 therapy (18) with significantly improved clinical outcomes, but where the vast majority of patients develop IRAEs with combination therapy (19).…”

Section: Discussionmentioning

confidence: 99%

Immune Toxicities Elicted by CTLA-4 Blockade in Cancer Patients Are Associated with Early Diversification of the T-cell Repertoire

et al. 2017

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While immune checkpoint blockade elicits efficacious responses in many cancer patients, it also produces a diverse and unpredictable number of immune-related adverse events (IRAE). Mechanisms driving IRAE are generally unknown. Because CTLA-4 blockade leads to proliferation of circulating T cells, we examined in this study whether ipilimumab treatment leads to clonal expansion of tissue-reactive T cells. Rather than narrowing the T cell repertoire to a limited number of clones, ipilimumab induced greater diversification in the T cell repertoire in IRAE patients compared to patients without IRAE. Specifically, ipiliumumab triggered increases in the numbers of clonotypes, including newly detected clones and a decline in overall T cell clonality. Initial broadening in the repertoire occurred within 2 weeks of treatment, preceding IRAE onset. IRAE patients exhibited greater diversity of CD4+ and CD8+ T cells, but showed no differences in regulatory T cell numbers relative to patients without IRAE. PSA responses to ipilimumab were also associated with increased T cell diversity. Our results show how rapid diversification in the immune repertoire immediately after checkpoint blockade can be both detrimental and beneficial for cancer patients.

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Section: Discussionmentioning

confidence: 99%

Immune Toxicities Elicted by CTLA-4 Blockade in Cancer Patients Are Associated with Early Diversification of the T-cell Repertoire

et al. 2017

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“…Both ipilimumab and pembrolizumab were administered through an intravenous infusion, and no prophylactic drugs were used. Treatment-related AEs were managed according to relevant guidelines [8,[9][10][11][12]. Blood tests, liver and kidney function tests, urine and stool examinations, adrenal gland function tests, thyroid function tests, pituitary hormone tests, and ECG were performed at the baseline and before each treatment dose.…”

Section: Methodsmentioning

confidence: 99%

Safety of immune checkpoint inhibitors in Chinese patients with melanoma

et al. 2016

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This study aimed to determine the tolerability of Chinese melanoma patients, particularly those with hepatitis B virus (HBV) infection, to immune checkpoint inhibitor therapy. Patients with metastatic melanoma who received anti-cytotoxic T lymphocyte-associated antigen-4 antibody (ipilimumab) or anti-programmed death 1 antibody (pembrolizumab) therapy at our hospital between August 2012 and July 2015 were retrospectively reviewed. Adverse events were evaluated according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 3.0. Twenty-three patients with advanced melanoma were included; nine and 10 patients received infusions of ipilimumab and pembrolizumab, respectively, whereas four patients received concurrent ipilimumab and pembrolizumab therapy. There was no cessation of treatment because of agent-related adverse events in any patient. Immune-related adverse events were observed in 44% (4/9), 60% (6/10), 100% (4/4), and 61% (14/23) of patients receiving ipilimumab, pembrolizumab, concomitant ipilimumab and pembrolizumab, and any treatment, respectively. The most frequent immune-related adverse events were endocrine disorders (39%, 9/23), liver function abnormalities (22%, 5/23), and dermatological events (17%, 4/23). There were no gastrointestinal reactions. Toxicities were usually mild and easily managed; only 13% (3/23) of patients had grade 3 adverse events and none experienced grade 4 events or treatment-related death. No additional toxicity nor severe hepatotoxicity was observed in 11 patients who had previous HBV infection. The recommended anti-cytotoxic T lymphocyte-associated antigen-4 and anti-programmed death 1 antibody doses were well tolerated by Chinese patients. Thus, immune checkpoint inhibitors appear to be effective and safe in metastatic melanoma patients, including those with pre-existing HBV infection.

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“…[23] Ipilimumab-induced diarrhea has been associated with bowel perforation and subsequent death. [24] This side effect has also been seen in patients treated with anti-PD-1 therapy. The onset of symptoms has been observed within 6–7 weeks following the initiation of ipilimumab treatment, and 6–18 weeks in patients treated with PD-1 blockade.…”

Section: Gastrointestinal Side Effectsmentioning

confidence: 97%

Immune checkpoint inhibitors: An innovation in immunotherapy for the treatment and management of patients with cancer

Dine

Gordon

Shames

et al. 2017

Asia-Pacific Journal of Oncology Nursing

175

138

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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.

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Optimal management of immune-related toxicities associated with checkpoint inhibitors in lung cancer

Cited by 44 publications

References 49 publications

Immune Toxicities Elicted by CTLA-4 Blockade in Cancer Patients Are Associated with Early Diversification of the T-cell Repertoire

Immune Toxicities Elicted by CTLA-4 Blockade in Cancer Patients Are Associated with Early Diversification of the T-cell Repertoire

Safety of immune checkpoint inhibitors in Chinese patients with melanoma

Immune checkpoint inhibitors: An innovation in immunotherapy for the treatment and management of patients with cancer

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