Frailty matters: Association of mFI-5 Index with odds of mortality, hospitalization, and toxicities with ADCs, BiTE, and CAR T-cell therapies in real-world data.

Abstract

11002 Background: Targeted-delivery biopharmaceuticals such as antibody–drug conjugates (ADCs) or BiTE cell therapy are increasingly used in oncology. Recent meta-analyses demonstrate similar survival benefits of ADCs in younger and older patients across tumor types; however, baseline frailty predicts increased mortality, toxicity and hospitalization among patients receiving systemic anticancer therapy. While NCCN guidelines recommend frailty assessment for older adults prior to surgery, no such guidance exists for systemic treatments. Methods: We conducted a retrospective cohort study using TriNetX, a federated real-world data network with anonymized EHRs from hundreds of healthcare organizations. We included 46,674 patients with solid tumors, breast and bladder (solid ca) and 15,213 patients with hematologic cancers such as lymphoma, leukemia (heme ca) who initiated ADCs, BiTE-cell therapy, or CAR T-cell therapy. Cohort entry was defined as the first use of the drug class (index date). Toxicities, i.e. cardiotoxicity or cytopenia were outcomes if occurred within 30 days of index; patients without these events or with other outcomes served as comparators. Baseline frailty was measured using the modified Frailty Index-5 (mFI-5), derived from ICD-10 codes for hypertension (I10), care dependency (Z74), diabetes (E08–E13), COPD (J44), and heart failure (I50). Logistic regression estimated associations between frailty and each outcome, with p-values adjusted using the Benjamini–Hochberg false discovery rate. Mortality at pre-specified time points and hospitalization were fitted with a Cox proportional hazards model with frailty category as the primary exposure, controlling for age, and stratifying by cancer group and treatment. Results: In heme ca and solid ca, higher mFI-5 relative to mFI=0 was associated with significantly increased odds of toxicities with ADCs, including nausea, thrombocytopenia, anemia, cardiotoxicity, diarrhea, lung disease, and neutropenia (all p<0.001). In heme ca, higher mFI-5 was associated with significantly higher odds of toxicities, including anemia and cardiotoxicity (all p<0.001) with BiTE therapy and CAR T-cell. Results indicate a strong relationship between frailty severity and mortality risk (Table 1) and hospitalization after controlling for age and accounting for differences in baseline hazard across cancer groups and treatment strata. Conclusions: Assessing frailty severity through mFI-5 before initiating targeted systemic therapy in hematologic and solid tumors may help identify patients at increased risk of poor survival odds, adverse effects and facilitate shared treatment decision-making. Hazard ratio of mortality relative to mFI=0. mFI-5 score Hazard ratio of mortality with 95% CI 1 1.41 [1.34-1.47] 2 1.79 [ 1.69-1.9] 3 2.45 [2.24-2.69] 4+ 2.51 [2.11-2.97]