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  • 1
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. e21549-e21549
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. e21549-e21549
    Abstract: e21549 Background: The incorporation of ICI into the treatment of melanoma has greatly improved patient outcomes, but this benefit has come at the cost of exposing patients to immune-related adverse events (irAEs). A wide spectrum of irAE types has been described, and severity is known to vary from minor to life-threatening; however, the literature to date on the chronicity of irAEs is limited. Objectives: To characterize the long-term and permanent irAEs associated with ICI treatment in patients with melanoma, the treatment of irAEs and the association with survival outcomes. Methods: We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥6 months), transient (resolution over a period 〈 6 months), or no irAEs. Overall survival was evaluated for those patients that were treated in the metastatic setting with PD1 inhibitor monotherapy. Results: Thirty-eight patients were treated in the adjuvant setting and 123 patients were treated in the metastatic setting. A total of 279 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, 15 (9.3%) experienced long-term irAEs as their longest-lasting toxicity, 34 (21.1%) developed transient irAEs only, and 46 (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (35.5%) or skin-related (32.7%). Grade ≥3 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still on treatment for long-term or permanent irAEs 6 months or more following completion of ICI therapy, including 23 patients on thyroid replacement and 22 on oral steroids. ICI treatment was temporarily interrupted for 63 (22.6%) irAEs and permanently discontinued due to irAE in 38 (13.6%) patients. Subgroup analysis of patients who received single-agent ICI in the first-line palliative setting reveals that those with longer-duration irAEs had a significantly longer median overall survival. Conclusions: Despite the significant benefits, treatment with ICIs in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients. The risk of long-term toxicity should therefore be discussed when obtaining consent for treatment. As these treatments are being used more commonly in the adjuvant setting, the impact of survivorship and the long-term management of these toxicities is increasingly important.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 2
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Melanoma Research Vol. 33, No. 1 ( 2023-02), p. 50-57
    In: Melanoma Research, Ovid Technologies (Wolters Kluwer Health), Vol. 33, No. 1 ( 2023-02), p. 50-57
    Abstract: The aim of this study was to evaluate overall survival post-treatment discontinuation survival (OS PTD ) in advanced melanoma patients started on immunotherapy. This retrospective study included all unresectable advanced or metastatic melanoma patients who had permanent treatment discontinuation after receiving at least one cycle of palliative-intent programmed death-1 ± cytotoxic T-lymphocyte associated protein-4 inhibitor treatment from 2014 to 2019. Indications of permanent treatment discontinuation included treatment completion, toxicity or progression. OS PTD was defined as a time of permanent treatment discontinuation to the time of death. Our study ( N  = 96) had 27, 12 and 57 patients who discontinued PD-1 inhibitor treatment due to treatment completion, toxicity and progression, respectively. Median treatment durations received for the treatment completion, toxicity and progression groups were 24, 6 and 3 months, respectively. As expected those patients who had disease progression on immunotherapy had very poor survival compared to those that completed treatment or stopped due to toxicity. A multivariable Cox model excluding the patients who progressed indicated no significant OS PTD differences between the toxicity and treatment completion group (HR, 0.894; 95% CI, 0.232–3.449; P  = 0.871) who received single or dual immunotherapy. Our real-world study highlighted similar, durable survival at PD-1 inhibitor discontinuation due to either toxicity or treatment completion, despite longer treatment duration received in the completion group than toxicity group. Patients with progression on PD-1 inhibitor treatment have very poor survival. Our findings must be interpreted with caution due to its retrospective nature and small sample size.
    Type of Medium: Online Resource
    ISSN: 0960-8931
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 1095779-0
    detail.hit.zdb_id: 2030780-9
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  • 3
    In: Immunotherapy, Future Medicine Ltd, Vol. 14, No. 10 ( 2022-07), p. 765-776
    Abstract: Plain language summary Several previous studies have suggested that obesity may be correlated with improved efficacy of immunotherapy and raised the concern that obesity may be associated with increased immunotoxicity; however, other studies have not replicated these findings. The authors evaluated the records from one center of 409 patients with advanced cancer on immune checkpoint inhibitors. There was no difference with respect to adverse events, treatment response or survival between obese and nonobese patients.
    Type of Medium: Online Resource
    ISSN: 1750-743X , 1750-7448
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2022
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  • 4
    Online Resource
    Online Resource
    Future Medicine Ltd ; 2022
    In:  Immunotherapy Vol. 14, No. 1 ( 2022-01), p. 23-30
    In: Immunotherapy, Future Medicine Ltd, Vol. 14, No. 1 ( 2022-01), p. 23-30
    Abstract: Aim: To evaluate the correlation between venous thromboembolism events (VTEs) and immune checkpoint inhibitor (ICI)-based regimens. Methods: This is a retrospective study of 403 patients with advanced cancer on ICI-based regimens. Results: We report 8% VTE incidence post-ICI initiation over a median of 11.1 months of follow-up. Compared with single-agent ICI, dual-ICI was significantly correlated with higher incidence of VTE (odds ratio [OR]: 4.196, 95% CI: 1.527–11.529, p = 0.005), but chemotherapy–immuno-oncology combination was not (OR: 1.374, 95% CI: 0.285–6.632, p = 0.693). Subsequent systemic therapy post-ICI was also independently associated with higher VTE incidence (OR: 2.599, 95% CI: 1.169–5.777, p = 0.019). Conclusion: Our findings suggest potential underreporting of VTE incidence in ICI clinical trials. As dual-ICI is becoming more prevalent in cancer management, clinicians should maintain vigilance regarding VTE in patients with advanced cancer on ICI-based regimens.
    Type of Medium: Online Resource
    ISSN: 1750-743X , 1750-7448
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2022
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  • 5
    In: Melanoma Management, Future Medicine Ltd, Vol. 9, No. 1 ( 2022-03)
    Abstract: Aim: To evaluate the efficacy of dual versus single immune checkpoint inhibitors (ICI) in BRAF wild-type advanced melanoma patients. Materials & methods: A retrospective study of all advanced BRAF wild-type melanoma patients on palliative-intent ICI between 2015 and 2020 (n = 67). Results: Dual ICI had better overall survival (OS) when compared with single ICI in BRAF wild-type patients (hazard ratio: 0.204; 95% CI: 0.064–0.649; p = 0.007), but lost its statistical significance (median OSl not reached vs 20.9 months; p = 0.213; adjusted hazard ratio: 0.475; 95% CI: 0.164–1.380; p = 0.171) when only including patients treated after 2018 when dual ICI was funded in our province. Dual ICI were significantly associated with more frequent (p = 0.005) and severe (p = 0.026) immune-related adverse events, and required more immune-related adverse events-indicated systemic corticosteroid use (p  〈  0.001) compared with single ICI. Conclusion: While limited by small sample size and retrospective nature, dual ICI may have non statistically significant trend toward better OS efficacy when compared with single ICI in BRAF V600 wild-type advanced melanoma patients.
    Type of Medium: Online Resource
    ISSN: 2045-0885 , 2045-0893
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2022
    detail.hit.zdb_id: 2786852-7
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  • 6
    Online Resource
    Online Resource
    MDPI AG ; 2022
    In:  Current Oncology Vol. 29, No. 10 ( 2022-10-20), p. 7953-7963
    In: Current Oncology, MDPI AG, Vol. 29, No. 10 ( 2022-10-20), p. 7953-7963
    Abstract: ICI therapy has greatly improved patient outcomes in melanoma, but at the cost of immune-related adverse events (irAEs). Data on the chronicity of irAEs, especially in real-world settings, are currently limited. We performed a retrospective chart review of 161 adult patients with melanoma treated with at least one cycle of ICI regimen in the adjuvant or metastatic setting: 129 patients received PD-1 inhibitor monotherapy and 32 received dual immunotherapy. Patients were grouped by duration of irAE: permanent (no complete resolution), long-term (resolution over a period ≥ 6 months), transient (resolution over a period 〈 6 months), or no irAEs. A total of 283 irAEs were reported in the whole patient population. Sixty-six (41.0%) patients developed permanent irAEs, fifteen (9.3%) experienced long-term irAEs as their longest-lasting toxicity, thirty-four (21.1%) developed transient irAEs only, and forty-six (28.6%) experienced no irAEs. Permanent irAEs occurred in 21 (65.6%) patients treated with dual immunotherapy and in 45 (34.9%) patients treated with monotherapy. The majority of permanent irAEs were endocrine-related (36.0%) or skin-related (32.4%). Grade 3–4 permanent irAEs occurred in 20 (12.4%) patients and included toxicities such as adrenal insufficiency, myocarditis, and myelitis. Fifty-three (32.9%) patients were still requiring treatment for long-term or permanent irAEs 6 months or more following the completion of ICI therapy, including twenty-four patients on thyroid hormone replacement and twenty-two on oral steroids. ICI treatment was temporarily interrupted for 64 (22.6%) irAEs and permanently discontinued due to irAEs in 38 patients (13.6% of irAEs, 23.6% of patients); additionally, 4 (2.5%) patients died of irAEs. Our findings show that ICI treatment in melanoma is associated with a wide range of toxicities that can be permanent and may have long-lasting impacts on patients, which should therefore be discussed when obtaining consent for treatment.
    Type of Medium: Online Resource
    ISSN: 1718-7729
    Language: English
    Publisher: MDPI AG
    Publication Date: 2022
    detail.hit.zdb_id: 2270777-3
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  • 7
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Journal of Immunotherapy Vol. 44, No. 9 ( 2021-11), p. 362-370
    In: Journal of Immunotherapy, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. 9 ( 2021-11), p. 362-370
    Abstract: Immunotherapy has revolutionized treatment outcomes in numerous cancers. However, clinical trials have largely excluded patients with autoimmune diseases (ADs) due to the risk of AD flares or predilection for developing organ-specific inflammation. The objective of this study was to evaluate the safety and efficacy of immunotherapy in patients with cancer and preexisting ADs. A retrospective, single-center study of patients with cancer initiated on immune checkpoint inhibitors between 2012 and 2019 was conducted. The primary outcome was the development of immune-related adverse events (irAEs) with respect to the presence of AD at baseline. Associations were assessed using Kaplan-Meier curves, bivariate and multivariable analyses. Of the 417 patients included in this study, 63 patients (15%) had preexisting ADs. A total of 218 patients (53%) developed at least 1 irAE. There was no association between the presence of baseline AD on the development, grade, or number of irAEs; time to irAE or irAE recovery; systemic corticosteroid or additional immunosuppressant treatment for irAEs; permanent treatment discontinuation; or overall response rate. Two smaller cohorts were studied, melanoma and non–small cell lung cancer, and there was no effect of baseline AD on overall survival on either cohort. However, a greater proportion of patients with baseline ADs had full recovery from their irAE ( P =0.037). Furthermore, age below 65, baseline steroid use, and single-agent immunotherapy regimens were protective in terms of the development of irAEs. Our study suggests that immune checkpoint inhibitors have similar safety and efficacy profiles in patients with preexisting ADs.
    Type of Medium: Online Resource
    ISSN: 1524-9557
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 2048797-6
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  • 8
    In: Immunotherapy, Future Medicine Ltd, Vol. 14, No. 10 ( 2022-07), p. 777-787
    Abstract: Aim: To evaluate overall survival in advanced cancer patients who achieved complete response (CR) with immune checkpoint inhibitor (ICI) therapy. Methods: This retrospective study included patients with advanced unresectable or metastatic cancer who received at least one cycle of palliative-intent ICI. Best overall response was used to define response groups. Results: 21 (7%) of 322 patients achieved CR. Multivariate analysis demonstrated that CR was independently associated with better overall survival compared with disease progression (hazard ratio: 0.012; 95% CI: 0.002–0.090) and stable disease (hazard ratio: 0.063; 95% CI: 0.009–0.464) as well as a nonsignificant trend toward better overall survival compared with partial response (hazard ratio: 0.169; 95% CI: 0.023–1.252) regardless of cancer type, ICI regimen or ICI line. Conclusion: Patients who achieved CR had longer survival compared with patients who did not achieve CR.
    Type of Medium: Online Resource
    ISSN: 1750-743X , 1750-7448
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2022
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  • 9
    Online Resource
    Online Resource
    Future Medicine Ltd ; 2023
    In:  Immunotherapy Vol. 15, No. 11 ( 2023-08), p. 819-826
    In: Immunotherapy, Future Medicine Ltd, Vol. 15, No. 11 ( 2023-08), p. 819-826
    Abstract: Tweetable abstract Later time of day of the first several infusions of immune checkpoint inhibitors was associated with worse overall survival in patients with advanced melanoma.
    Type of Medium: Online Resource
    ISSN: 1750-743X , 1750-7448
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2023
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