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We present accretion disk size measurements for 15 luminous quasars at 0.7 ≤ z ≤ 1.9 derived from griz light curves from the Dark Energy Survey. We measure the disk sizes with continuum reverberation mapping using two methods, both of which are derived from the expectation that accretion disks have a radial temperature gradient and the continuum emission at a given radius is well described by a single blackbody. In the first method we measure the relative lags between the multiband light curves, which provides the relative time lag between shorter and longer wavelength variations. From this, we are only able to constrain upper limits on disk sizes, as many are consistent with no lag the 2σ level. The second method fits the model parameters for the canonical thin disk directly rather than solving for the individual time lags between the light curves. Our measurements demonstrate good agreement with the sizes predicted by this model for accretion rates between 0.3 and 1 times the Eddington rate. Given our large uncertainties, our measurements are also consistent with disk size measurements from gravitational microlensing studies of strongly lensed quasars, as well as other photometric reverberation mapping results, that find disk sizes that are a factor of a few (∼3) larger than predictions. [ABSTRACT FROM AUTHOR]

Background: The impact of immunosuppressive therapy (IST) on immune-checkpoint inhibition (ICI) is unclear., Methods: Patients with unresectable advanced melanoma (MM) treated with ICI in the years 2011-2020 were identified from the prospective multicenter German skin cancer registry ADOREG. Patients with IST within 60 days before, or within 30 days after start of ICI were compared to patients without IST. End points were disease control rate (DCR), overall survival (OS) and progression-free survival (PFS) determined by Kaplan-Meier method. Prognostic factors were evaluated in a Cox regression model., Results: Of 814 patients treated with ICI, 73 (9%) received concomitant IST, mainly steroids. Patients with brain metastases (BM) received IST more frequently (n = 34/130 patients; 26%), than patients without BM (39/684 patients; 6%). In patients without BM, IST initiated before, but not IST initiated after start of ICI was significantly associated with worse PFS (univariate hazard ratio (HR) 2.59, 95% confidence interval (95%-CI) 1.07-6.28, p = 0.035; multivariate HR 3.48, 95%-CI 1.26-9.6, p = 0.016). There was no association between IST and OS or DCR. In patients with BM, IST initiated before, but not after start of ICI was significantly associated with worse OS (univariate HR 2.06, 95%-CI 1.07-3.95, p = 0.031; multivariate HR 5.91, 95%-CI 1.74-20.14, p = 0.004). There was no association between IST and PFS or DCR., Conclusion: Patients receiving IST 60 days before start of ICI showed a tendency to an impaired therapy outcome. IST initiated within 30 days after start of ICI, mainly due to early side effects, did not affect the efficacy of ICI therapy., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Corinna Kochanek: None. Catharina Gilde: None. Lisa Zimmer: served as consultant and/or has received honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, and Sunpharma and travel support from Merck Sharp & Dohme, Bristol Myers Squibb, Pierre Fabre, Sunpharma, Sanofi and Novartis; outside the submitted work. Selma Ugurel: declares research support from Bristol Myers Squibb and Merck Serono; speakers and advisory board honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, and Novartis; and meeting and travel support from Almirall, Bristol-Myers Squibb, IGEA Clinical Biophysics, Merck Sharp & Dohme, Novartis, Pierre Fabre, and Sun Pharma; outside the submitted work. Friedegund Meier: has received travel support or/and speaker’s fees or/and advisor’s honoraria by Novartis, Roche, Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre, Sanofi and Immunocore and research funding from Novartis and Roche; outside the submitted work. Jochen Utikal: is on the advisory board or has received honoraria and travel support from Amgen, Bristol-Myers Squibb, GSK, Immunocore, LeoPharma, Merck Sharp and Dohme, Novartis, Pierre Fabre, Roche, Sanofi; outside the submitted work. Claudia Pföhler: received honoraria (speaker honoraria or honoraria as a consultant) and travel support from: Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Merck Serono, Celgene, AbbVie, Sunpharma, Pierre Fabre, UCB, Nutricia Milupa, Janssen and LEO; outside the submitted work. Rudolf Herbst: is an employee of Helios Kliniken Erfurt GmbH. Sebastian Haferkamp: declares research support from Bristol Myers Squibb speakers and advisory board honoraria from Bristol Myers Squibb, Merck Sharp & Dohme, Pierre Fabre and Novartis; outside the submitted work. Julia Welzel: has received honoraria and travel support from Almirall, Bristol Myers Squibb, Novartis, Pierre Fabre and Merck Sharp & Dohme; outside the submitted work. Pia Dücker: declares research support from Bristol Myers Squibb, Merck and Novartis. Speakers and advisory board honoraria from Bristol Myers Squibb, Roche, Sanofi-Aventis, AbbVie, Merck Sharp and Dohme and Pierre Fabre; outside the submitted work. Ulrike Leiter: reports research support from Merck Sharp and Dohme, consulting fees and honoraria from Sun Pharma, Sanofi (personal and institutional), Merck Sharp and Dohme (personal and institutional), Novartis, Roche, Almirall Hermal, support for attending meeting from Sun Pharma and participation on a Data Safety Monitoring Board or Advisory Board from Sun Pharma, Sanofi, Merck Sharp and Dohme, Novartis, Roche, Almirall Hermal; outside the submitted work. Michael Weichenthal: None. Imke von Wasielewski: Honoraria: Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Stemline, Kyowa Kirin. Consultant or Advisory Role: Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi; Travel, Accommodations. Expenses: Novartis, Bristol Myers Squibb, Merck Sharp & Dohme, Sanofi, Stemline, Kyowa Kirin; outside the submitted work. Yenny Angela: None. Ralf Gutzmer: declares research support from Novartis, Amgen, Sanofi, Merck-Serono, Admiral, SUN Pharma and Kyowa-Kirin; honoraria for lectures from Roche Pharma, Bristol-Myers Squibb, Novartis, Merck Sharp & Dohme. Almirall, Amgen, Merck-Serono, SUN Pharma, Pierre-Fabre, and Sanofi; advisory honoraria from Roche Pharma, Bristol-Myers Squibb, Novartis, Merck Sharp & Dohme, Almirall, Amgen, Pierre-Fabre, Merck-Serono, 4SC, Sun Pharma, Merck-Serono, Sanofi, and Immunocore; outside the submitted work., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aim: Immune checkpoint inhibition (ICI) triggers immune-related adverse events (irAEs). The relevance of lipase elevation remains unclear., Patients and Methods: Skin cancer patients with newly detected serum lipase elevation (at least twofold upper normal limit) or newly diagnosed type I diabetes mellitus upon ICI therapy were retrospectively collected at 14 German skin cancer centres., Results: We identified 68 patients with lipase elevation occurring after a median time of 19 (range 1-181) weeks on ICI, 15 (22%) thereof had symptoms consistent with pancreatitis. Forty-seven patients (73%) had other irAE, mainly colitis. Discontinuation (n = 24, 35%) or interruption (n = 26, 38%) of ICI resulted in decrease of lipase after reinduction of ICI lipase levels increased again in 12 of 24 patients. In 18 patients (27%), ICI was continued unchanged, and in 12 (67%) of them, lipase levels normalised. Twenty-two patients were identified with newly diagnosed type I diabetes mellitus related to ICI, and 12 (55%) thereof had also lipase elevation mainly shortly before or after the diagnosis of diabetes. Fourteen (64%) patients had other irAE, mainly thyroiditis. Irrespective of lipase elevation, patients frequently showed a rapid onset with ketoacidosis, decreased c-peptide, and strongly increased blood glucose levels., Conclusion: Increased serum lipase during ICI is often not associated with pancreatitis but with other irAE as possible cause. Therefore, it might be sufficient to regularly monitor blood glucose levels and perform further workup only in case of signs or symptoms of pancreatitis and/or exocrine pancreas insufficiency., Competing Interests: Conflict of interest statement Honoraria: R.G. (Roche, BMS, MSD, Novartis, Amgen, Merck Serono, Almirall Hermal, SUN, Sanofi, Pierre Fabre), C.P. (Roche, BMS, MSD, Novartis, Merck Serono, Celgene, AbbVie, LEO), L.Z. (Roche, BMS, MSD, Novartis, Sanofi, Pierre Fabre), K.-M.T. (Roche, BMS, MSD, Novartis, Pierre Fabre, LEO, Galderma, Candela, CSL Behring), K.C.K. (Merck sharp and Dohme, Novartis and Bristol Myers Squibb and travel support from Novartis), J.C.H. (BMS, MSD, Roche, Novartis, Sanofi), S.U. (BMS, MSD, Merck Serono, Novartis and Roche), C.B. (Roche, BMS, MSD, Novartis, Sanofi-Aventis), D.D. (MSD, Novartis, Roche, Sanofi), J.U. (Amgen, Bristol Myers Squibb, GSK, LEO Pharma, Merck Sharp and Dohme, Novartis, Pierre Fabre, Roche, Sanofi), R.H. (Roche, BMS, MSD, Novartis, Pierre Fabre), L.H. (BMS, Roche, Novartis, MSD, Amgen, CureVac, Sanofi, Pierre Fabre), C.L. (Roche, Pierre Fabre, Novartis, BMS, MSD, Merck, Almirall Hermall, Sun Pharma, Sanofi, BioNTech, Kyowa Kirin), F.M. (Novartis, Roche, BMS, MSD, Pierre Fabre), I.G. (Novartis, Roche, BMS, MSD, Sanofi), T.K.E. (Roche, Pierre Fabre, Novartis, BMS, MSD, Sanofi). Consultant or Advisory Role: R.G. (BMS, Roche, Novartis, Almirall Hermal, MSD, Amgen, SUN, Sanofi, Pierre Fabre, Merck Serono, Bayer, Pfizer), C.P. (Roche, Novartis, Merck Serono), L.Z. (MSD, BMS, Novartis, Pierre Fabre, Sanofi), K.-M.T. (Roche, BMS, MSD, Novartis, Pierre Fabre, LEO, CSL Behring) K.C.K. (BMS, MSD, Novartis, Pierre Fabre), J.C.H. (MSD, Sun Pharma, Pierre Fabre), S.U. (BMS, MSD, Merck Serono, Novartis and Roche), C.B. (Roche, BMS, MSD, Novartis, Merck Serono, Sanofi-Aventis, Pierre Fabre), D.D. (Novartis, Roche, Sanofi), J.U. (Amgen, Bristol Myers Squibb, GSK, Leo Pharma, Merck Sharp and Dohme, Novartis, Pierre Fabre, Roche, Sanofi), R.H. (Roche, BMS, Novartis, Pierre Fabre), L.H. (BMS, Roche, Novartis, MSD, Amgen, Curevac, Sanofi, Pierre Fabre), C.L. (Roche, Pierre Fabre, Novartis, BMS, MSD, Merck, Almirall Hermal, Sun Pharma, Sanofi, BioNTech, Kyowa Kirin), F.M. (Novartis, Roche, BMS, MSD, Pierre Fabre), I.G. (Novartis, Roche, BMS, MSD, Sanofi), T.K.E. (Roche, Pierre Fabre, Novartis, BMS, MSD, Sanofi). Research Funding: R.G. (Novartis, Pfizer, Johnson & Johnson, Amgen, Merck Serono, SUN Pharma, Sanofi), L.Z. (Novartis), K.C.K. (Novartis, Merck Sharp and Dohme), J.C.H. (BMS), S.U. (BMS, Merck Serono), J.U. (Apogenix, NOXXON Pharma, Elsalys Biotech, TILT Biotherapeutics, BioNTech RNA Pharmaceuticals, RHEACELL, Merck), L.H. (Novartis), F.M. (Novartis, Roche), I.G. (Roche, Pfizer, Novartis). Travel, Accommodations, Expenses: R.G. (Roche, BMS, SUN, Merck Serono, Pierre Fabre), C.P. (Roche, BMS, MSD, Novartis, Merck Serono, Celgene, AbbVie, LEO), L.Z. (BMS, Pierre Fabre, Amgen, Sanofi, Sun Pharma, Novartis), K.-M.T. (Roche, BMS, MSD, Novartis, Pierre-Fabre, LEO, Candela) K.C.K. (MSD, Novartis and Bristol Myers Squibb, Novartis), J.C.H. (Pierre Fabre, BMS), S.U. (BMS, MSD), D.D. (Amgen, BMS, MSD, Mylan, Novartis, Pierre Fabre, Roche, Sanofi), J.U. (Amgen, Bristol Myers Squibb, GSK, Leo Pharma, Merck Sharp and Dohme, Novartis, Pierre Fabre, Roche, Sanofi), C.L. (Roche, Pierre Fabre, Novartis, BMS, MSD, Merck, Almirall Hermall, Sun Pharma, Sanofi, BioNTech, Kyowa Kirin), F.M. (Novartis, Roche, BMS, MSD, Pierre Fabre), I. G. (Novartis, Roche, BMS, MSD). Stock ownership: none. Patent application/registration: none. Employment: none. No conflict of interest: C.R. and C.K. had no conflict of interest., (Copyright © 2021 Elsevier Ltd. All rights reserved.)