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      Psychological Distress of Metastatic Melanoma Patients during Treatment with Immune Checkpoint Inhibitors: Results of a Prospective Study

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          A large proportion of patients with metastatic melanoma suffer from psychological distress. Early identification of these patients is important to be able to offer them adequate support. This longitudinal study aimed to investigate the extent to which the psychological distress of patients with malignant melanoma might change during their first three months of treatment with immune checkpoint inhibitors. We found a high proportion of distressed patients in a cohort of 113 patients at the beginning of immunotherapy, which decreased during therapy. A binary logistic regression analysis provided additional factors indicating an increased risk of developing distress—female gender and occurrence of adverse events correlated significantly with distress values above the threshold. The strongest factor was patients’ self-assessment. When initiating immunotherapy, it is also important to consider the needs of patients and offer them psycho-oncological support.

          Abstract

          Background: Immune checkpoint inhibitors (ICI) provide effective treatment options for advanced melanoma patients. However, they are associated with high rates of immune-related side effects. There are no data on the distress of melanoma patients during their ICI treatment. We, therefore, conducted a prospective longitudinal study to assess distress and the need for psycho-oncological support in these patients. Methods: Questionnaires were completed before initiation of ICI (T0), after 6–8 weeks (T1), and after 12–14 weeks (T2). We furthermore included the Hornheide Screening Instrument (HSI), distress thermometer (DT), and patients’ self-assessment. Binary logistic regression was performed to identify factors indicating a need for psychooncological support. Results: 36.3%/55.8% (HSI / DT) of the patients were above the threshold, indicating a need for psychooncological support at T0, and 7.8% of the patients reported practical problems. In contrast, at T2, the distress values had decreased to 29.0%/40.2% (HSI/DT), respectively. Female gender and occurrence of side effects significantly correlated to values above the threshold. The strongest factor was the patient’s self-assessment. Conclusion: With the beginning of ICI, psychooncological support should be offered. Furthermore, practical problems should be considered, e.g., transport to therapy. Female patients and patients with side effects should be given special attention, as well as the patient self-assessment.

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          Most cited references33

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          Five-Year Survival with Combined Nivolumab and Ipilimumab in Advanced Melanoma

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            Immune-Related Adverse Events Associated with Immune Checkpoint Blockade

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              Nivolumab in Previously Untreated Melanoma withoutBRAFMutation

              Nivolumab was associated with higher rates of objective response than chemotherapy in a phase 3 study involving patients with ipilimumab-refractory metastatic melanoma. The use of nivolumab in previously untreated patients with advanced melanoma has not been tested in a phase 3 controlled study. We randomly assigned 418 previously untreated patients who had metastatic melanoma without a BRAF mutation to receive nivolumab (at a dose of 3 mg per kilogram of body weight every 2 weeks and dacarbazine-matched placebo every 3 weeks) or dacarbazine (at a dose of 1000 mg per square meter of body-surface area every 3 weeks and nivolumab-matched placebo every 2 weeks). The primary end point was overall survival. At 1 year, the overall rate of survival was 72.9% (95% confidence interval [CI], 65.5 to 78.9) in the nivolumab group, as compared with 42.1% (95% CI, 33.0 to 50.9) in the dacarbazine group (hazard ratio for death, 0.42; 99.79% CI, 0.25 to 0.73; P<0.001). The median progression-free survival was 5.1 months in the nivolumab group versus 2.2 months in the dacarbazine group (hazard ratio for death or progression of disease, 0.43; 95% CI, 0.34 to 0.56; P<0.001). The objective response rate was 40.0% (95% CI, 33.3 to 47.0) in the nivolumab group versus 13.9% (95% CI, 9.5 to 19.4) in the dacarbazine group (odds ratio, 4.06; P<0.001). The survival benefit with nivolumab versus dacarbazine was observed across prespecified subgroups, including subgroups defined by status regarding the programmed death ligand 1 (PD-L1). Common adverse events associated with nivolumab included fatigue, pruritus, and nausea. Drug-related adverse events of grade 3 or 4 occurred in 11.7% of the patients treated with nivolumab and 17.6% of those treated with dacarbazine. Nivolumab was associated with significant improvements in overall survival and progression-free survival, as compared with dacarbazine, among previously untreated patients who had metastatic melanoma without a BRAF mutation. (Funded by Bristol-Myers Squibb; CheckMate 066 ClinicalTrials.gov number, NCT01721772.).
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Cancers (Basel)
                Cancers (Basel)
                cancers
                Cancers
                MDPI
                2072-6694
                27 May 2021
                June 2021
                : 13
                : 11
                : 2642
                Affiliations
                [1 ]Department of Dermatology, University Hospital Tübingen, 72076 Tübingen, Germany; wiens_lisa@ 123456web.de (L.W.); thomas.eigentler@ 123456med.uni-tuebingen.de (T.E.); claus.garbe@ 123456med.uni-tuebingen.de (C.G.)
                [2 ]Department of Psychosomatic Medicine and Psychotherapy, University Hospital Tübingen, 72076 Tübingen, Germany; Norbert.Schaeffeler@ 123456med.uni-tuebingen.de
                Author notes
                [* ]Correspondence: andrea.forschner@ 123456med.uni-tuebingen.de ; Tel.: +49-7071-29-84555
                Author information
                https://orcid.org/0000-0001-8530-780X
                https://orcid.org/0000-0002-6185-4945
                Article
                cancers-13-02642
                10.3390/cancers13112642
                8198252
                34072206
                3d79db01-00d0-4e9f-9bbe-dd1e856dae5d
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( https://creativecommons.org/licenses/by/4.0/).

                History
                : 27 April 2021
                : 25 May 2021
                Categories
                Article

                metastatic melanoma,checkpoint inhibitors,immune therapy,psychooncology,distress,his,dt,problems

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