{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T13:17:50Z","timestamp":1778591870516,"version":"3.51.4"},"reference-count":30,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Using real-world data, this study evaluates the use of ADCs over a decade across six University of California (UC) medical centers, focusing on the incidence of neutropenia-related adverse effects and associated clinical outcomes. Methods: A real-world retrospective study utilizing UC Health Data Warehouse records of patients receiving at least one dose of the ten most-used ADCs at one of the 6 UC hospitals between 2012 and 2024. The outcomes evaluated in this study were grade 3+ neutropenia and febrile neutropenia (FN) during any treatment cycle, and healthcare utilization outcomes including G-CSF prophylaxis, hospital and ICU admission, and mortality. Multivariate logistic regression was conducted to identify predictors for neutropenia-related events after the first dose of ADC. Results: Data from 3511 patients (mean \u00b1 SD age: 56.7 \u00b1 17.6 years) were analyzed. The most commonly observed cancer types were breast cancer (43.4%), lymphoid, hematopoietic (41.8%), and urinary tract cancer (13.4%). The top three most commonly prescribed ADCs were fam-trastuzumab deruxtecan (22.6%), ado-trastuzumab emtansine (19.4%), and brentuximab vedotin (18.1%). Their respective all-cycle rates of FN were 5.4%, 1.2%, and 10.4%, while grade 3+ neutropenia rates were 16.4%, 5.1%, and 40.1%. Gemtuzumab ozogamicin and inotuzumab ozogamicin were associated with the highest rates of FN (both 18.1%), and inotuzumab ozogamicin was associated with the highest rates of hospital admissions (27.1%), ICU admissions (3.8%), and deaths (5.2%). Anemia and immunodeficiency disorders were identified as predictors for first-dose FN among patients receiving ADCs. Conclusions: Real-world data from this large multi-center cohort showed substantial variation in neutropenia-related events across ADCs. As ADC use continues to grow, these findings highlight the need for vigilant monitoring and proactive supportive care.<\/jats:p>","DOI":"10.3390\/cancers18101563","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:33:37Z","timestamp":1778589217000},"page":"1563","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Incidence\u00a0of Clinically Significant Neutropenia and Complications Related to Antibody-Drug Conjugates: A Real-World Study at the University of California"],"prefix":"10.3390","volume":"18","author":[{"given":"Tiffany","family":"Jan","sequence":"first","affiliation":[{"name":"School of Pharmacy & Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA"},{"name":"UC Irvine Health, Orange, CA 92868, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miranda","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy & Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-5525-6651","authenticated-orcid":false,"given":"Fan-Ying","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Pharmacy & Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Kuderer","sequence":"additional","affiliation":[{"name":"Division of Hematology, Department of Medicine, University of Washington Medical Center, Seattle, WA 98195, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4391-4219","authenticated-orcid":false,"given":"Alexandre","family":"Chan","sequence":"additional","affiliation":[{"name":"School of Pharmacy & Pharmaceutical Sciences, University of California, Irvine, CA 92697, USA"},{"name":"UC Irvine Health, Orange, CA 92868, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1038\/s41392-022-00947-7","article-title":"Antibody drug conjugate: The \u201cbiological missile\u201d for targeted cancer therapy","volume":"7","author":"Fu","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1186\/s13045-025-01704-3","article-title":"Antibody-Drug Conjugates (ADCs): Current and future biopharmaceuticals","volume":"18","author":"Wang","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Corti, C., Giugliano, F., Nicol\u00f2, E., Ascione, L., and Curigliano, G. (2021). Antibody-Drug Conjugates for the Treatment of Breast Cancer. Cancers, 13.","DOI":"10.3390\/cancers13122898"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Zhang, F., and Li, S. (2025). Antibody-drug conjugates as game changers in bladder cancer: Current progress and future directions. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1591191"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"107078","DOI":"10.1016\/j.leukres.2023.107078","article-title":"Antibody-drug conjugate [ADC] treatment of leukaemia","volume":"131","author":"Hassan","year":"2023","journal-title":"Leuk. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2230618","DOI":"10.1080\/19420862.2023.2230618","article-title":"Therapeutic index improvement of antibody-drug conjugates","volume":"15","author":"Gerber","year":"2023","journal-title":"MAbs"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gogia, P., Ashraf, H., Bhasin, S., and Xu, Y. (2023). Antibody-Drug Conjugates: A Review of Approved Drugs and Their Clinical Level of Evidence. Cancers, 15.","DOI":"10.3390\/cancers15153886"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1186\/s13045-025-01752-9","article-title":"Overcoming resistance to antibody-drug conjugates: From mechanistic insights to cutting-edge strategies","volume":"18","author":"Zhou","year":"2025","journal-title":"J. Hematol. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1002\/cncr.34507","article-title":"Treatment-related adverse events of antibody-drug conjugates in clinical trials: A systematic review and meta-analysis","volume":"129","author":"Zhu","year":"2023","journal-title":"Cancer"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"102113","DOI":"10.1016\/j.eclinm.2023.102113","article-title":"Toxicity profile of antibody-drug conjugates in breast cancer: Practical considerations","volume":"62","author":"Verrazzo","year":"2023","journal-title":"EClinicalMedicine"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Rao, M., Wu, L., Chen, H., Wu, X., Wang, H., Chen, Y., and Chen, C. (2025). Hematological toxicity of anti-tumor antibody-drug conjugates: A retrospective pharmacovigilance study using the FDA adverse event reporting system. PLoS ONE, 20.","DOI":"10.1371\/journal.pone.0334513"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1080\/14740338.2025.2449991","article-title":"Hematological toxicities in antibody-drug conjugates related with breast cancer: A pharmacovigilance study using FDA adverse event reporting system database","volume":"25","author":"Wang","year":"2026","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gui, X., Zhao, J., Ding, L., Chai, J., Lai, H., Cai, Y., Luo, S., Zeng, Y., Wu, W., and Chen, H. (2023). Assessing real-world safety concerns of Sacituzumab govitecan: A disproportionality analysis using spontaneous reports in the FDA adverse event reporting system. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1276976"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"100095","DOI":"10.1016\/j.esmorw.2024.100095","article-title":"Real-world safety and effectiveness data of trastuzumab deruxtecan and sacituzumab govitecan in breast cancer: A Hellenic Cooperative Oncology Group study","volume":"7","author":"Fountzilas","year":"2025","journal-title":"ESMO Real. World Data Digit. Oncol."},{"key":"ref_15","unstructured":"UCLA Clinical and Translational Science Institute (2025, May 29). UC Health Data Warehouse (UCHDW). Published 15 January 2025. Available online: https:\/\/ctsi.ucla.edu\/uc-health-data-warehouse-uchdw."},{"key":"ref_16","first-page":"2787","article-title":"Hospitalizations, outcomes, and management costs of febrile neutropenia in patients from a managed care population","volume":"25","author":"Kawatkar","year":"2017","journal-title":"Support Care Cancer"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"3257","DOI":"10.1182\/blood.V126.23.3257.3257","article-title":"Risk of Febrile Neutropenia (FN) in Select Myelosuppressive Chemotherapy Regimens","volume":"126","author":"Family","year":"2015","journal-title":"Blood"},{"key":"ref_18","unstructured":"US Department of Health and Human Services (2024, August 01). Common Terminology Criteria for Adverse Events (CTCAE) Common Terminology Criteria for Adverse Events (CTCAE) V5.0, Available online: https:\/\/ctep.cancer.gov\/protocoldevelopment\/electronic_applications\/docs\/CTCAE_v5_Quick_Reference_5x7.pdf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1093\/annonc\/mdm525","article-title":"Cost of neutropenic complications of chemotherapy","volume":"19","author":"Weycker","year":"2008","journal-title":"Ann. Oncol."},{"key":"ref_20","unstructured":"(2025, January 05). NCCN Clinical Practice Guidelines in Oncology. Hematopoietic Growth Factors. Version 2.2025 [Internet]. Available online: https:\/\/www.nccn.org\/professionals\/physician_gls\/pdf\/growthfactors.pdf."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1007\/s10637-017-0520-6","article-title":"Clinical toxicity of antibody-drug conjugates: A meta-analysis of payloads","volume":"36","author":"Masters","year":"2018","journal-title":"Investig. New Drugs"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"635","DOI":"10.1002\/onco.13715","article-title":"Effects of Ado-Trastuzumab Emtansine and Fam-Trastuzumab Deruxtecan on Metastatic Breast Cancer Harboring HER2 Amplification and the L755S Mutation","volume":"26","author":"Mukohara","year":"2021","journal-title":"Oncologist"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1002\/cncr.21326","article-title":"Final report of the efficacy and safety of gemtuzumab ozogamicin (Mylotarg) in patients with CD33-positive acute myeloid leukemia in first recurrence","volume":"104","author":"Larson","year":"2005","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1056\/NEJMoa1509277","article-title":"Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia","volume":"375","author":"Kantarjian","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"116","DOI":"10.4103\/0974-2727.163126","article-title":"Febrile Neutropenia in Hematological Malignancies: Clinical and Microbiological Profile and Outcome in High Risk Patients","volume":"7","author":"Lakshmaiah","year":"2015","journal-title":"J. Lab. Physicians"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"103309","DOI":"10.1016\/j.eclinm.2025.103309","article-title":"Prevention of sacituzumab govitecan-related neutropenia and diarrhea in patients with HER2-negative advanced breast cancer (PRIMED): An open-label, single-arm, phase 2 trial","volume":"85","author":"Gion","year":"2025","journal-title":"EClinicalMedicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1159\/000540354","article-title":"Enfortumab Vedotin-Induced Febrile Neutropenia and Hyperglycemia Successfully Treated with Multidisciplinary Treatment Including Continuous Hemodialysis Filtration and Insulin Injection in a Patient with Chemo-Resistant Metastatic Urothelial Carcinoma: A Case Report","volume":"17","author":"Otsuka","year":"2024","journal-title":"Case Rep. Oncol."},{"key":"ref_28","first-page":"124","article-title":"Overview of antibody-drug conjugates nonclinical and clinical toxicities and related contributing factors","volume":"8","author":"Cheng","year":"2025","journal-title":"Antib. Ther."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"pkad069","DOI":"10.1093\/jncics\/pkad069","article-title":"Toxicity profiles of antibody-drug conjugates for anticancer treatment: A systematic review and meta-analysis","volume":"7","author":"Suzuki","year":"2023","journal-title":"JNCI Cancer Spectr."},{"key":"ref_30","first-page":"243","article-title":"Primary prophylaxis with G-CSF may improve outcomes in patients with newly diagnosed advanced-stage Hodgkin lymphoma treated with brentuximab vedotin plus chemotherapy","volume":"191","author":"Straus","year":"2020","journal-title":"Br. J. Haematol."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/10\/1563\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T12:54:26Z","timestamp":1778590466000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/10\/1563"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,12]]},"references-count":30,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["cancers18101563"],"URL":"https:\/\/doi.org\/10.3390\/cancers18101563","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,12]]}}}