A Prospective Geriatric Assessment (GA) Study Predicting Toxicities in Older Adults (OA) with Non-Hodgkin Lymphoma (NHL): Timed up and Go Test (TUG) Time Emerges As a Functional Vital Sign
Authors: Torka Pallawi , Drill Esther , Ganesan Nivetha , Truong Regina , Qiu Annie , Ramos Amador Walter , Oliveros Mayan , Boardman Alexander P. , Caron Philip , David Kevin A. , Epstein-Peterson Zachary D. , Falchi Lorenzo , Ghione Paola , Horwitz Steven , Intlekofer Andrew M. , Johnson William T. , Kumar Anita , Lue Jennifer Kimberly , Luttwak Efrat , Moskowitz Alison , Noy Ariela , Owens Colette , Palomba Maria Lia , Steiner Raphael E. , Stuver Robert , Vardhana Santosha A. , Zelenetz Andrew D. , Salles Gilles , Hamlin Paul A. 
Published: December 2024

Introduction
Sixty percent of newly diagnosed NHL patients (pts) are ≥60 years (yrs). Toxicity (tox) is more common in older adults (OA), and those who experience it derive less benefit from treatment. We conducted a prospective study to determine if a geriatric assessment (GA) or its component measures predict tox in OA with NHL and if changes in GA during and after treatment correlate with tox. The timed up and go (TUG) test measures how long it takes a pt to stand up, walk 10 feet, turn, walk back, and sit down again. We previously reported that TUG time was independently associated with severe tox (STox) in OA with NHL treated with chemotherapy (chemo) (Torka et al, ASH 2023). In this abstract, we report the quantitative effect of baseline TUG time and correlation between changes in TUG time during therapy on likelihood of STox with each cycle of chemo.
Methods
Pts ≥ 60 yrs with NHL starting a new chemo regimen were included. GA was performed before pre-phase therapy (for a subset of pts), before chemo initiation, before each cycle and 1 month after last chemo. A full panel of GA instruments was utilized to assess physical function, cognition, depression, nutrition, polypharmacy, and social support as previously reported (Torka et. Al, ASH 2023).
Therapeutic regimens were at the discretion of the physician, characterized prior to initiation as curative intent or palliative. The primary endpoint was STox, defined as any of the following: 1) Hospitalization during or within 30 days post chemotherapy, 2) Dose delay or reduction to a dose intensity ≤80% of the planned dose intensity, 3) Discontinuation of chemo due to tox, 4) Death. Secondary tox endpoints were Grade 3 or higher (3+) non-hematologic tox and Grade 4 or higher (4+) hematologic tox.
Results
A total of 194 pts were enrolled, one pt was missing baseline data, but was included in endpoint analysis. Median age was 74 yrs (range 60-93 yrs), 39% were women, majority had diffuse large B cell lymphoma (DLBCL) (72%), advanced stage disease (77%) and received R-CHOP (72%). Median activity of daily living (ADL) score was 85 (range 0-100) and median instrumental ADL (IADL) score was 14 (range 4-14). The median TUG time was 10 seconds (sec) (range 3.2-50 in able pts), and 30% pts had an abnormal TUG test (defined as ≥ 12 sec). Majority of pts (60%) had a normal nutritional status.
STox occurred in 57% pts, 25% had grade 3+ non-hematologic tox and 38% had grade 4+ hematologic tox. Toxicity events happened in every cycle, and many patients experienced multiple toxicity events across cycles. The 5-year progression free survival (PFS) was 85% (CI 79%, 91%) and 5-year overall survival (OS) was 77% (CI 71%, 84%). Pts experiencing STox were older (76 vs 71 yrs, p=0.005), more likely to be ADL dependent (p=0.019), IADL dependent (p=0.014), have lower patient reported KPS (p&lt;0.001), poor nutritional status (p=0.029) and abnormal TUG at baseline (p&lt;0.001).
Increasing baseline TUG was linearly associated with recurrent STox during chemo. For pts with no Stox (n=83), median TUG was 8.8 sec (IQR 7.6, 10.8); for pts with 1-3 STox events (n=96), median TUG was 10 sec (IQR 8 -15.7); and for pts with STox during 4+ cycles (n=14, p&lt;0.001) median TUG was 15 sec (IQR 10.4-24.1). For each 1-sec increase in baseline TUG score, the odds of a STox event throughout all cycles were increased by a factor of 1.1 (p=0.008), equating to an 11% increase in the odds of having STox with each 1-sec increase. By example, a 5-sec and 10-sec increase would increase STox odds by a factor of 1.7 and 2.8, respectively. A logistic longitudinal mixed effects model showed that change in TUG time between cycles was not significant in predicting STox, but rather it was the TUG score itself which had the effect at any given cycle, and the effect was similar to that of the TUG baseline score analysis. A higher TUG time was also associated with increased G3+ non heme (p=0.01), G4+ heme toxicities (p=0.001), lower PFS (p=0.001) and OS (p=0.005).
Conclusions
An abnormal TUG time (≥12 sec) at baseline and prior to each cycle of chemo is associated with STox in OA with NHL, with each 1-sec increase in TUG score increasing the odds of a STox event by 11%. A TUG time is a simple and effective tool, easy to perform in clinic, that may inform toxicity assessment through treatment. Prospective validation of this tool will facilitate future implementation into daily practice.