{ "abstract": "Background Immune checkpoint therapies (ICTs) can trigger life-threatening immune-related adverse events (irAEs) such as myocarditis, myositis, and myasthenia gravis (MG), with mortality approaching 50%, often requiring ICT discontinuation. 1 High-dose corticosteroids are first-line but carry risks including infection, hyperglycemia, delirium, and osteoporosis. While T-cell and macrophage infiltrates are well described, emerging evidence implicates B-cell involvement in irAE pathogenesis.2 3 Myocarditis and overlap syndromes may represent distinct immunologic phenotypes, offering opportunities for targeted intervention. In the absence of validated alternatives to steroids, we implemented an Early Targeted Biologics (ETB) algorithm combining corticosteroids with plasmapheresis (autoantibody/ICT clearance), rituximab (anti-CD20 for B-cell depletion), and infliximab (anti-TNF-a for T-cell and potential myeloid suppression). We hypothesized ETB would improve outcomes in ir-myositis, ir-myocarditis, and/or MG compared to routine care.Methods This single-center retrospective cohort study included patients with renal, urothelial, or prostate cancer hospitalized for ir-myositis, ir-myocarditis, and/or MG between December 2014 and April 2025. Diagnoses followed published criteria integrating clinical presentation, creatine kinase or troponin, acetylcholine receptor antibody, electrodiagnostic studies (EKG, EMG), cardiac MRI, and biopsy when available. 4 5Patients received ETB or routine care (steroids ± immunosuppressants per provider discretion). Clinical endpoints included anticancer therapy resumption, hospital length of stay (LOS), ICU admission, time to physiologic steroid dose (≤ 10 mg/day prednisone), major adverse cardiac events (MACE), 6-month infection rate, and 30-day rehospitalization.6 7 Continuous variables were compared using Mann-Whitney U tests; categorical variables using Fisher’s exact or Chi-squared tests.Results Forty-nine patients were included (ETB n = 34; routine n = 15), with comparable age, sex, cancer type, and ICT ( table 1). Male predominance reflected cancer epidemiology. irAEs included isolated myositis (34.7%), myocarditis (20.4%), MG (16.3%), and overlap syndromes (≥2 diagnoses; 28.6%). ETB reduced median LOS to 11 days (IQR 10.0 – 15.8) vs 25 days (IQR 11.5 – 36.5; p= 0.013), with fewer ICU admissions (17.6% vs 66.7%; p=0.002) and higher anticancer therapy resumption (58.8% vs 13.3%; p=0.005) (figure 1). MACE incidence trended lower in ETB (5.9% vs. 26.7%; p= 0.06). Median time to physiologic steroid taper was numerically shorter in ETB (32 vs 59.5 days; p= 0.16). Thirty-day rehospitalization (32.4% vs 26.7%; p=0.75) and 6-month infection rates (45.2% vs 54.5%; p=0.73) were similar.Conclusions ETB was associated with shorter LOS, fewer ICU admissions, and higher rates of anticancer therapy resumption without increased infections. Prospective multicenter studies are warranted to validate these findings, refine therapeutic algorithms, and identify predictive biomarkers for irAE management.References Wang DY, Salem JE, Cohen JV, Chandra S, Menzer C, Ye F, Johnson DB. Fatal toxic effects associated with immune checkpoint inhibitors: a systematic review and meta-analysis. JAMA Oncol. 2018;4(12),1721–1728. doi:10.1001/jamaoncol.2018.3923Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Moslehi JJ. Fulminant myocarditis with combination immune checkpoint blockade. N Engl J Med. 2016;375(18):1749–1755. doi:10.1056/NEJMoa1609214Siddiqui BA, Durand J-B, Gao J, Wang J, Aparicio A, Campbell MT, Subudhi SK. Clinical and immunological analyses of immune checkpoint inhibitor-associated neuromuscular (NM) toxicities. Journal of Clinical Oncology. 2019;37(15_suppl), e14118-e14118. doi:10.1200/JCO.2019.37.15_suppl.e14118Bonaca MP, Olenchock BA, Salem JE, Wiviott SD, Ederhy S, Cohen A, Moslehi J. Myocarditis in the setting of cancer therapeutics: proposed case definitions for emerging clinical syndromes in cardio-oncology. Circulation. 2019;140(2):80–91. doi:10.1161/CIRCULATIONAHA.118.034497Plomp L, Chassepot H, Psimaras D, Maisonobe T, Mensi E, Leonard-Louis S, Allenbach, Y. Features of myositis and myasthenia gravis in patients treated with immune checkpoint inhibitors: a multicentric, retrospective cohort study. Lancet Reg Health Eur. 2025;50, 101192. doi:10.1016/j.lanepe.2024.101192Molina GE, Zubiri L, Cohen JV, Durbin SM, Petrillo L, Allen IM, Reynolds KL. Temporal trends and outcomes among patients admitted for immune-related adverse events: a single-center retrospective cohort study from 2011 to 2018. Oncologist. 2021;26(6):514–522. doi:10.1002/onco.13740Galloway JB, Hyrich KL, Mercer LK, Dixon WG, Fu B, Ustianowski AP, British Society for Rheumatology Biologics, R. Anti-TNF therapy is associated with an increased risk of serious infections in patients with rheumatoid arthritis especially in the first 6 months of treatment: updated results from the british society for rheumatology biologics register with special emphasis on risks in the elderly. Rheumatology (Oxford). 2011;50(1):124–131. doi:10.1093/rheumatology/keq242Abstract 1057 Table 1Baseline characteristics of patients with ir-myositis, ir-myocarditis, and/or MG treated with routine care versus ETBICT, immune checkpoint therapy; PD-1, programmed death 1; CTLA-4, cytotoxic T lymphocyte-associated protein-4; * p-value <0.05Abstract 1057 Figure 1Clinical outcomes of patients with ir-myositis, ir-myocarditis, and/or MG receiving ETB compared to routine care. ETB significantly reduced hospital length of stay and ICU admissions and increased anticancer therapy resumption. MACE incidence and time to physiologic steroid taper were lower with ETB but not statistically significant. * p < 0.05, ** p < 0.005", "authors": [ { "affiliations": [ "Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Lily Chen" }, { "affiliations": [ "Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Keila C Ostos-Mendoza" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Omar Alhalabi" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Ana Aparicio" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "John C Araujo" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Matthew T Campbell" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Paul G Corn" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Monica Desai" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Jianjun Gao" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Sangeeta Goswami" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Andrew W Hahn" }, { "affiliations": [ "Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Bagi Jana" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Eric Jonasch" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Craig A Kovitz" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "John K Lin" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Pavlos M Msaouel" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Patrick Pilie" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Amishi Y Shah" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Padmanee Sharma" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Arlene O Siefker-Radtke" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Nizar M Tannir" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Amado J Zurita" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Jianbo Wang" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Anishia Rawther-Karedath" }, { "affiliations": [ "Department of Clinical Pharmacy Programs, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Emily Wang" }, { "affiliations": [ "Department of Stem Cell Transplantation and Cellular Therapy, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Chitra Hosing" }, { "affiliations": [ "Department of Interventional Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Rahul A Sheth" }, { "affiliations": [ "Department of Rheumatology and Clinical Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Huifang Lu" }, { "affiliations": [ "Department of Neuro-Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Ashley Aaroe" }, { "affiliations": [ "Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Christopher Logothetis" }, { "affiliations": [ "Department of Cardiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Nicolas Palaskas" }, { "affiliations": [ "The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Bilal A Siddiqui" }, { "affiliations": [ "The University of Texas MD Anderson Cancer Center, Houston, TX, USA" ], "name": "Sumit K Subudhi" } ], "title": "1057 Early targeted biologics are associated with improved clinical outcomes in immune-related myocarditis, myositis, and myasthenia gravis", "uid": "512f2629-5153-51c1-9895-33bebbee191f" }