The side effect registry immuno-oncology (SERIO) - A tool for systematic analysis of immunotherapy-induced side effects.

Background: Immunotherapies such as immune checkpoint inhibitors (ICI) are effective in multiple tumor entities but induce a plethora of side effects. Comprehensive real-world analyses are essential to identify new signals, characterize diagnostic features, enable risk assessment, determine pathomechanisms, assess effectiveness of side effect management and compare tumor outcomes.
Methods: The international online `Side-Effect Registry Immuno-Oncology´ (SERIO; www.serio-registry.org) collects rare, complex, and severe immunotherapy-induced side effects across all tumor entities with a strong focus on ICI-induced immune-related adverse events (irAE). The relational database management system (RDMS) contains structured data on patient and tumor characteristics, type of immunotherapy, treatment of side effects, and outcome of tumor and irAE. Data are captured within 25 organ modules including new modules for immune effector cell-associated neurotoxicity syndrome (ICANS) for CAR-T-cell therapies and cytokine release syndrome (CRS) for bispecific antibodies. Information on biological samples is gathered.
Results: A total of 1398 irAE cases have been documented by 58 centers from 13 countries in patients with 17 tumor types. IrAEs were induced by nine different immunotherapies including tebentafusp and CAR-T cell therapies, and resulted, among others, in neurological (7.6%), pulmonary (4.0%), and cardiac toxicities (2.9%). 50.0% of all irAEs were graded severe or life-threatening and 23.0% of patients received second-line therapy for steroid-refractory or steroid-dependent irAE. SERIO has contributed to 44 original publications on topics ranging from irMyocarditis to irEncephalitis to long-term persistent sequelae of immunotherapy.
Conclusions: A reliable evidence base is crucial for decision-making in rare, complex or therapy-refractory irAE. SERIO can help optimize side effect management and thereby reduce morbidity and mortality induced by immunotherapy.
Competing Interests: Declaration of Competing Interest LH received speaker and consultancy fees from BiomeDx, BMS, Kyowa Kirin, Merck, MSD, Myoncare, Novartis, Pierre-Fabre, Roche, Sanofi, SUN and Therakos. The LMU received research grants or clinical study grants from Agenus, AstraZeneca Inc., BMS, Hoffmann-La Roche AG, Huya Bioscience, Immunocore, IO Biotech, Merck, Merck Sharp & Dome GmbH, Miltenyi Biomedicine GmbH, Novartis, Pfizer, Pierre Fabre, Regeneron, Replimune, and Sanofi Aventis. AF received honoraria for presentations and travel support from: BMS, Novartis, Pierre-Fabre. AF reports on participation on Advisory Boards of MSD, BMS, Novartis, Pierre-Fabre, Immunocore and institutional research grants from BMS Stiftung Immunonkologie for other financial or non-financial interests. AH reports grants and personal fees from Amgen, grants and personal fees from BMS, grants and personal fees from MerckPfizer, grants and personal fees from MSD/Merck, grants and personal fees from Philogen, grants and personal fees from Pierre Fabre, grants and personal fees from Regeneron, grants and personal fees from Roche, grants and personal fees from Sanofi-Genzyme, grants and personal fees from Novartis Pharma, grants and personal fees from Eisai, personal fees from Immunocore, grants and personal fees from Replimune, personal fees from Seagen, personal fees from IO Biotech, personal fees from Dermagnostix, personal fees from Incyte, grants and personal fees from NeraCare, personal fees from Highlight Therapeutics, grants from Huya Biosciences, personal fees from Kyowa Kirin, personal fees from Iovance, outside the submitted work. CL received honoraria (lectures, presentations, speakers bureaus, manuscript writing or educational events) and travel support from: BMS, MSD Merck, Pierre-Fabre, Biontech, Almirall Hermal, Sun Pharma, KyowaKirin, Immunocore, Sanofi, Novartis. CP received honoraria (speaker honoraria or honoraria as a consultant) and travel support from: Novartis, BMS, MSD, Merck Serono, MSD, Celgene, AbbVie, Sunpharma, Pierre Fabre, UCB, Nutricia Milupa, Janssen and LEO outside the submitted work. CR reports personal consulting fees from BMS, Roche, MSD, Sanofi, Pierre Fabre, Sunpharma, Pfizer, Regeneron. CR received honoraria (lectures, presentations, speakers bureaus, manuscript writing or educational events) from Pierre Fabre, Sanofi, BMS. CR reports personal fees (participation on a Data Safety Monitoring Board or Advisory Board) from Ultimovacs and Regeneron. CR reports stocks/stock options: Ribonexus. DS reports grants, personal fees, non-financial support and other from Novartis, BMS, Amgen, MSD & Array/Pfizer; personal fees and from 4SC, Agenus, Array BioPharma, Astra Zeneca, BioAlta, CureVac, Daiichi Sanyko, Erasma, Haystack, Immatics, Immunocore, InFlarX, Merck Serono, Pierre Fabre, PamGene, Philogen, Neracare NoviGenix, Ultimovacs, Sandoz/Hexal, Sanofi, Seagen, Sun Pharma, Regeneron, and Replimune. GMcA reports on grants or contracts from BMS, Genentech-Roche, Merck to his institution. DT reports consultancy, speaker fees or travel grants: BMS, Roche, Novartis, Sanofi, Recordati, Kyowa Kirin, Sun Pharma and Pierre Fabre. GMcA reports on participation on Data Safety Monitoring or Advisory Board from Pierre Fabre and Pfizer (no payments) and on National Breast Cancer Foundation Board (Australia) (no payments). GVL is consultant advisor for Agenus, Amgen, Array Biopharma, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Evaxion, Hexal AG (Sandoz Company), Highlight Therapeutics S.L., Innovent Biologics USA, Merck Sharpe & Dohme, Novartis, OncoSec, PHMR Ltd, Pierre Fabre, Provectus, Qbiotics, Regeneron. HG reports on grants or contracts from BMS, Roche, MSD Oncology, Amgen, Novartis, Iovance Biotherapeutics to her institution. HG received consulting fees from BMS, MSD Oncology, Pierre Fabre, Sanofi/ Regeneron. HG received speakers honoraria from BMS, MSD Oncology, Pierre-Fabre, Sanofi/ Regeneron. HG received travel support from MSD, Amgen, Pfizer. JH received scientific grants from BMS, Sanofi, Sunpharma and consulting fees (for advisory boards) from GSK, MSD, Pierre Fabre, Onkowiessen, Sunpharma. JH received honoraria (talks) from Amgen, BMS, GSK, Immunocore, MSD, Novartis, Pierre Fabre, Sanofi, Sunpharma. JH received meeting/travel support from BMS, Iovance, Sunpharma. JH reports on participation on a Data Safety Monitoring Board from Nekvax. LZ declares speakers and advisory board honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Sanofi, Sunpharma, research support from Novartis and travel support from Merck Sharp & Dohme, Bristol-Myers Squibb, Pierre Fabre, Sanofi, Sunpharma and Novartis; outside the submitted work. MS reports on research support from Amgen, BMS/Celgene, Gilead/Kite, Janssen, Miltenyi, Novartis, Roche, Seattle Genetics, Takeda. MS reports on participation on Advisory Boards of Astra Zeneca, Avencell, Ichnos, Incyte, Janssen, Molecular Partners. MS received honoraria (speaker’s bureau) from: Amgen, BMS/Celgene, Janssen, Gilead/Kite, Novartis, Pfizer, Takeda. PA reports on grants and contracts from BMS, Roche-Genentech, Pfizer, Sanofi. PA received consulting fees from Bristol Myers Squibb, Roche-Genentech, Merck, Sharp & Dohme, Novartis, Merck Serono, PierreFabre, Sun Pharma, Sanofi, Sandoz, Italfarmaco, Nektar, Pfizer, Lunaphore, Medicenna. Bio-Al Health, ValoTx, Replimmune, Bayer. PA received travel support from Pfizer, BIO-AI Health, Replimmune. PA reports on participation on a Data Safety Monitoring or Advisory Board from BMS, Roche-Genentech, Merck, Sharp & Dohme, Novartis, AstraZeneca, BoehringerIngelheim, Eisai, Regeneron, Daiichi Sankyo, Oncosec, Nouscom, Seagen, iTeos, Erasca. RD has intermittent, project focused consulting and/or advisory relationships with Novartis, Merck Sharp & Dhome (MSD), Bristol-Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, T3 Pharma, MaxiVAX SA, Pfizer, Simcere and touchIME outside the submitted work. RG received honoraria for advice and lectures from BristolMyers Squibb, Roche Pharma, MerckSharpDohme, Novartis, Merck-Serono, Amgen, Almirall Hermal, Pierre-Fabre, Sun Pharma, Immunocore, 4SC, Delcath, Sanofi/Regeneron. Ralf Gutzmer received travel support from SUN Pharma, Boehringer Ingelheim and PierreFabre. Ralf Gutzmer received research grants from Novartis, Sanofi/Regeneron, Merck Serono, Amgen, SUN Pharma, KyowaKirin, Admiral Hermal. RK received meeting and travel support from SunPharma, Novartis, Pierre-Fabre. SG reports on clinical trials honoraria to institution from MSD, BMS, Sanofi, Pfizer, BioNTech, EORTC, I-O Biotech, Astra Zeneca, and Regeneron. SG received consulting fees from MSD and BMS and an Online Ticket for ASCO from BMS. TE received speaker and consultancy fees from BMS, Curevac, Merck, MSD, Novartis, Pierre-Fabre, Sanofi, Almiral Hermal, and SUN. TN reports on grants or contracts from NIH, BMS, Astra Zeneca to his institution. TN received consulting fees from Genentech, BMS, Roche, Sanofi, Roivant, Race Oncology. TN participated on Data Safety Monitoring Board/ Advisory Board from Genentech. TR declared speaker’s honoraria and travel grants from Therakos and SUN. AR, CE, MK, VM have declared no conflicts of interest. BR received support from BMS, Merck and Astrazeneca. BR received honoraria (for lectures, presentations, speakers bureaus, manuscript writing or educational events) from BMS, Merck and Astrazeneca. BR reports on participation on a Data Safety Monitoring Board or Advisory Board from BMS, Merck and Astrazeneca. All remaining authors have declared no conflicts of interest.
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