Time toxicity in ALL: Quantifying home days among adults with acute lymphoblastic leukemia Free

Background: Treatment-related time toxicity, the burden of time to receive medical care, is increasingly recognized as an important patient-centered outcome in oncology. Adults with acute lymphoblastic leukemia (ALL) experience a high burden of care delivery. This “time toxicity” has not been adequately quantified to inform treatment decision-making and supportive care. To address this gap, we sought to quantify the time toxicity in ALL and compare time toxicity based on disease characteristics, treatment regimen, and treatment response.

Methods: We conducted a retrospective cohort analysis of adult (18+) ALL patients treated at the University of North Carolina from 2007-2024. Data collected included demographics, disease characteristics, treatment, response, and date of last follow up. Administrative data was used to classify each day from diagnosis to cutoff as a “home day” or a day receiving medical care (“time toxicity”). The primary outcome was the proportion of home days of total days at relevant time points (120 days [d], 1 year [y]). Cutoff was defined as death, data censor, date of last follow-up, or loss to follow-up (confirmed or suspected due to no encounters within 12 months). Patients were included if administrative records were complete. The Kaplan Meier method and Cox proportional Hazards models were used for survival estimates. Kruskal Wallis tests were used for detecting differences in days at home across groups.

Results: A total of 354 patients were screened. After removing patients due to incomplete records, 136 patients (72 Philadelphia chromosome [Ph] negative [-neg], 57 Ph+, 7 T-ALL) were included in the final dataset. The mean age was 55 (range 18 – 93); 59% were male, 41% female; 63% were white, 16% were Black, 21% were other; 16% were Hispanic. Ph-neg patients received a pediatric-inspired (PI) regimen (40, 56%), HyperCVAD (22, 31%), mini-CVD with or without inotuzumab (8, 11%), or other (2, 3%). Most patients with Ph+ALL received HyperCVAD with a tyrosine kinase inhibitor [TKI] (43, 77%). Other regimens were TKI+steroids alone (9, 16%), PI regimen + TKI (3, 5%), and Blinatumomab+TKI (1, 2%). Remission was achieved after first-line therapy in 89.7% of patients (Ph-neg 89% with 26% MRD-negative, Ph+ 94% with 19% MRD-negative, T-ALL 57% with 28% MRD-negative). Median overall survival was 38.4 months [m] (Ph-neg 42.8 m, Ph+ Not reached, T-ALL 22.1 m). There was no survival difference between patients receiving HyperCVAD v. PI regimens (HR 0.79, p=0.64).

The median number of overall home days for all patients was 312 (IQR: 145-632). There was no significant difference in total home days by disease type. The proportion of days at home (PDH) by interval was 0.60_120d and 0.74_1y. In Ph-neg, there was no difference in overall home days with HyperCVAD v. PI regimens (median 358 v. 320, p=0.66); however, median days at home was significantly less at 120 days (63 v. 74, p=0.049) for adults receiving HyperCVAD; median days at home at 1 year was similar between regimens (239 v. 254, p=0.62). PDH in Ph+ALL was 0.63_120d and 0.77_1y. PDH in T-ALL was 0.61_120d and 0.71_1y. Days at home were not significantly different by remission status to first-line therapy at 120 days or 1 year.

Discussion: This is the first study to quantify the time burdens suffered by adults with ALL. Time toxicity for adults with ALL is very high—over 25% of total days in the first year are sacrificed to receive care—despite remission rates to first-line therapy approaching 90%. Time toxicity was similar across disease types. Patients with Ph-neg ALL receiving HyperCVAD had increased time toxicity in the first 4 months compared to those receiving pediatric-inspired regimens, though this became balanced at 1 year. These data can inform expectation setting as part of treatment decision-making and form the basis for future studies. Interventions to reduce time toxicity for adults with ALL are needed. The recent introduction of chemotherapy-free regimens (e.g. blinatumomab and/or inotuzumab) may substantially reduce time toxicity and increase time at home for patients with ALL. Future studies are needed to demonstrate these benefits.