Frailty Score Shows Link to Toxicity, Mortality Risk With Novel Cancer Therapies

Higher scores on the modified Frailty Index-5 (mFI-5) were significantly associated with greater odds of early toxicities and worse survival outcomes in patients with cancer receiving novel targeted therapies — including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and CAR T-cell therapy — according to data from a large real-world retrospective analysis presented at the 2026 ASCO Annual Meeting.

“Evaluating frailty through mFI-5 before initiating systemic therapy may identify patients [at risk for toxicity and survival odds,” Monali K. Vasekar, MD, Penn State College of Medicine, Hershey, Pennsylvania, said during a presentation of the data. “Assessing mFI-5 can help facilitate shared decision-making, and future clinical trial designs should incorporate frailty indices such as mFI-5 for prospective validation.”

The study evaluated more than 61,000 patients using the TriNetX database.

What does the mFI-5 index show following cancer treatment with novel therapies?

For oncology nurses caring for patients who may be candidates for these increasingly common novel therapies, the findings may reshape how pre-treatment frailty screening is approached and highlight the nursing team's role in identifying patients at heightened risk before therapy begins.

Investigators found that assessing mFI-5 — a five-item frailty index derived from ICD-10 diagnostic codes — prior to initiating targeted systemic therapy may help identify patients at increased risk of poor outcomes and inform shared treatment decision-making.

The mFI-5 is scored based on the presence or absence of 5 comorbidities captured in electronic health records: hypertension, heart failure, care dependency, chronic obstructive pulmonary disease (COPD), and diabetes mellitus. Each comorbidity present contributes 1 point to the score, ranging from 0 to 5. In this analysis, patients with mFI-5 scores of 1 or higher demonstrated significantly higher hazard ratios for both 1-year mortality and hospitalization compared with patients with a score of 0, with risk increasing in a dose-dependent fashion across all frailty severity levels.

What should oncology nurses know about the efficacy and outcomes findings of the frailty index?

Among the 46,674 patients with solid tumors and 15,213 patients with hematologic malignancies included in the analysis, the association between mFI-5 score and clinical outcomes appeared to be consistent.

For mortality, hazard ratios compared with mFI-5 of 0 ranged from 1.41 (95% CI, 1.34–1.47) at mFI-5 of 1 to 2.51 (95% CI, 2.11–2.97) at mFI-5 of 4 or higher. For 1-year hospitalization, hazard ratios ranged from 1.29 (95% CI, 1.26–1.33) at mFI-5 of 1 to 2.19 (95% CI, 1.93–2.48) at mFI-5 of 4 or higher — findings that remained consistent after controlling for age and stratifying by cancer group and treatment type.

Survival curves demonstrated a clear and progressive separation by frailty group over time. Patients with a frailty score of 0 maintained the highest adjusted survival probability across the full follow-up period, while patients with scores of 3 and 4 experienced substantially steeper declines.

The study cohort skewed toward lower frailty burden at baseline — 71.8% of solid tumor patients and 50.3% of hematologic malignancy patients had an mFI-5 score of 0 — yet even among patients with scores of 1 to 2, meaningful increases in toxicity, mortality, and hospitalization risk were observed.

For nurses involved in patient education and pre-treatment counseling, these data may help guide conversations about treatment expectations and the importance of baseline functional status assessment before novel therapies are initiated.

What toxicities did frail patients experience and what should nurses monitor?

In patients with solid tumors receiving ADC therapy, higher mFI-5 scores were associated with significantly increased odds of multiple toxicities within 30 days of treatment initiation, including nausea, diarrhea, lung disease, neuropathy, neutropenia, and liver toxicity. Odds ratios for nausea in solid tumor patients receiving ADCs ranged from 2.60 (95% CI, 2.43–2.78) at mFI-5 of 1 to 2.93 (95% CI, 2.02–4.25) at mFI-5 of 4 or higher. For lung disease — a particularly important toxicity given the interstitial lung disease risk profile of ADCs such as T-DXd — odds ratios escalated, reaching 15.63 (95% CI, 7.74–31.58) at the highest frailty scores.

In patients with hematologic malignancies receiving BiTE or CAR T-cell therapies, higher mFI-5 scores were associated with significantly higher odds of anemia, diarrhea, lung disease, neuropathy, neutropenia, and liver toxicity, with odds ratios for lung disease at mFI-5 of 4 reaching 7.95 (95% CI, 3.75–16.88). Cardiotoxicity and anemia were also prominent.

For oncology nursing teams monitoring patients in the early post-treatment period, these findings underscore the need for heightened surveillance of hematologic, gastrointestinal, pulmonary, and cardiac adverse events — especially in patients who enter treatment with any degree of baseline frailty.

What safety monitoring and frailty-informed care coordination practices should nurses prioritize?

The investigators emphasized that frailty is a dynamic and modifiable state, meaning that baseline mFI-5 assessment may create an opportunity for targeted pre-treatment intervention. Future studies may explore physical activity and exercise, nutritional optimization, psychosocial support, comorbidity management, lifestyle modifications and prehabilitation as strategies to mitigate frailty burden before therapy begins and potentially improve treatment tolerance and outcomes.

The study's limitations include its retrospective EHR design, which supports prognostic associations rather than causal conclusions; use of ICD-10 codes to define frailty and toxicities, which may under-capture clinically present frailty or adverse events; and imprecision in death timing derived from EHR activity.

Vasekar concluded that future clinical trial designs for ADC, BiTE, and CAR T-cell therapies should prospectively incorporate frailty indices such as mFI-5 to better characterize outcomes across the full spectrum of patient fitness.

Reference:

1. Strong AL, Petucci J, Fitzgerald B, Morales T, Honavar V, Vasekar MK. 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. J Clin Oncol. 2026;44(suppl 16:11002. doi:10.1200/JCO.2026.44.16_suppl.11002.