Incidence of Clinically Significant Neutropenia and Complications Related to Antibody-Drug Conjugates: A Real-World Study at the University of California

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 ± SD age: 56.7 ± 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.