Objective To compare psychometric functioning of the Fatigue Severity Scale (FSS) and the Modified Fatigue Impact Scale (MFIS) in a community sample of persons with multiple sclerosis (MS). Research Method A self-report survey including the FSS, MFIS, demographic and other health measures was completed by 1271 individuals with MS. Analyses evaluated the reliability and validity of the scales, assessed their dimensional structures, and estimated levels of floor and ceiling effects. Item response theory (IRT) was used to evaluate the precision of the MFIS and FSS at different levels of fatigue. Results Participants had a mean score on the FSS of 5.1 and of 44.2 on the MFIS. Cronbach’s alpha values for FSS and MFIS were all 0.93 or greater. Known-groups and discriminant validity of MFIS and FSS scores were supported by the analyses. The MFIS had low floor and ceiling effects, while the FSS had low floor and moderate ceiling effects. Unidimensionality was supported for both scales. IRT analyses indicate the FSS is less precise in measuring both low and high levels of fatigue compared to the MFIS. Conclusions Researchers and clinicians interested in measuring physical aspects of fatigue in samples whose fatigue ranges from mild to moderate can choose either instrument. For those interested in measuring both physical and cognitive aspects of fatigue, and whose sample is expected to have higher levels of fatigue, the MFIS is a better choice even though it is longer. IRT analyses suggest both scales could be shortened without a significant loss of precision.

Different mechanisms lead to immune checkpoint inhibitor (ICI) resistance. Identifying clinically useful biomarkers might improve drug selection and patients' therapy. We analyzed the soluble immune checkpoints sPD1, sPDL1, sLAG3, and sTIM3 using ELISA and their expression on circulating T cells using FACS in pre-and on-treatment blood samples of ICI treated melanoma patients. In addition, pretreatment melanoma metastases were stained for TIM3 and LAG3 expression by IHC. Results were correlated with treatment response and progression-free survival (PFS). Resistance to anti-PD1 treatment (n = 48) was associated with high pre-treatment serum levels of sLAG3 (DCR: p = .009; PFS: p = .018; ROC cutoff >148 pg/ml) but not sPD1, sPDL1 or sTIM3. In contrast, resistance to ipilimumab plus nivolumab (n = 42) was associated with high levels of sPD1 (DCR: p = .019, PFS: p = .046; ROC cutoff >167 pg/ml) but not sPDL1, sLAG3 or sTIM3. Both treatment regimens shared a profound increase of sPD1 serum levels with treatment (p < .0001). FACS analysis revealed reduced frequencies of CD3+ CD8+ PD1 + T cells (p = .028) in anti-PD1-resistant patients, whereas increased frequencies of CD3+ CD4+ LAG3 + T cells characterized patients resistant to ipilimumab plus nivolumab (p = .033). Unlike anti-PD1 monotherapy, combination blockade significantly increased proliferating T cells (CD3+ CD8+ Ki67 + T cells; p < .0001) and eosinophils (p = .001). In melanoma metastases, an increased infiltration with TIM3+ or LAG3 + T cells in the tumor microenvironment correlated with a shorter PFS under anti-PD1 treatment (TIM3: p = .019, LAG3: p = .07). Different soluble immune checkpoints characterized checkpoint inhibitor-resistant melanoma. Measuring these serum markers may have the potential to be used in clinical routine.

Aim: Autoimmune colitis is a typical and possible severe side effect among patients treated with ipilimumab. Patients & methods: We prospectively included 100 patients with metastasized melanoma under ipilimumab treatment in a radiological study of 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG PET-CT). PET evidence of pancolitis (‘PET-colitis’) was correlated with clinical variables. Results: We observed a significant correlation between PET-colitis and clinically significant diarrhoea, although PET-colitis was more frequent (49 vs 29% of patients, respectively). Neither PET-colitis nor diarrhoea was significantly correlated with response to therapy. Other immune-related adverse events, however, such as hypophysitis and hepatitis were associated with response to therapy and overall survival. Conclusion: Increased 18F-FDG uptake in the colon correlated with clinical symptoms but did not predict clinical outcome to ipilimumab.