Vulnerable Elders Survey (VES-13) and Longitudinal Analysis of Quality of Life in Indolent Non-Hodgkin Lymphoma: A Multi-Institutional Prospective Cohort Study

Background: Indolent non-Hodgkin lymphomas (iNHL) are incurable and disproportionately affect adults age >65 in whom frailty and functional impairment can impact disease management. The Vulnerable Elders Survey (VES-13) is a 13-item screening tool that incorporates age, self-rated health, physical function limitations, and functional disabilities to identify vulnerable older community-dwelling adults. Adults with a VES-13 score of >3 have a fourfold increased risk of death or functional decline over 2 years as compared to adults with a score <3 (Saliba et al, JAGS 2001). Our team previously showed that VES-13 >3 was associated with a higher risk of 1-year mortality in NHL (OR 3.26, 95% CI 2.15-4.96, Fama et al, ASH 2019), including in adults age <65. In this study, we determined whether VES-13 scores >3 were associated with quality of life (QOL) changes in adults with iNHL across the age spectrum.

Methods: We used the Lymphoma Epidemiology of Outcomes (LEO) Cohort Study to identify adults enrolled from 2015-2020 with grade 1-3A follicular and marginal zone lymphoma (FL, MZL) who completed the VES-13 at enrollment and QOL surveys at enrollment and follow-up. The LEO Cohort Study enrolls participants within 6 months of diagnosis and collects information on disease status, QOL, health behaviors, and patient-reported functional assessment. For this analysis we included QOL measured using the Functional Assessment of Cancer Therapy-General (FACT-G) at years 1 and 2 post-enrollment. The FACT-G total score was the sum of 4 subscales (range): physical (PWB, 0-28), social/family (SFWB, 0-28), emotional (EWB, 0-24), and functional (FWB, 0-28) well-being. A higher FACT-G total score (range 0-108) indicated better overall QOL. VES-13 scores ranged from 0 (lowest risk for death or decline) to 10+ (highest risk). Generalized linear mixed models evaluated changes in QOL from baseline based on VES-13 score >3 (vulnerable) vs <3 (non-vulnerable), within groups by age at enrollment >65 and <65.

Results: Our study included 1,186 participants: 42% age >65, 54% female, 84% non-Hispanic White, 10% Hispanic, 3.3% Black, and 1.4% Asian/Pacific Islander. Most (68%) were diagnosed with FL. FLIPI was high risk for 20%, and MALT-IPI was high risk for 23%. In the VES-13 <3 group, the mean (SD) baseline FACT-G total score was 86.5 (12.0), PWB 21.0 (3.5), SFWB 24.3 (4.3), EWB 18.8 (3.7), and FWB 22.3 (4.9). In the VES-13 >3 group, the mean (SD) baseline FACT-G total score was 70.4 (16.5), PWB 15.4 (5.6), SFWB 22.3 (5.5), EWB 17.5 (4.5), and FWB 15.3 (6.4); all significantly lower than the VES-13 >3 group (all p<0.01).

In adults <65, 63 (9%) had a VES-13 >3, which was associated with a significant improvement from baseline in PWB at years 1 and 2 when compared to VES-13 <3 (changes in baseline PWB were 2.1, 2.9 for VES-13 >3 vs 0.2, 0.1 for VES-13 <3, all p<0.05). Similarly, we observed improvement in FWB from baseline at years 1 and 2 in the VES-13 >3 vs <3 group (2.4, 2.9 vs 0.4, -0.1, respectively all p<0.05). The VES-13 >3 group had a decline in their EWB at 1 year vs the VES <3 group (-0.5 vs 1.2, respectively, p=0.003). At year 2, total FACT-G improved from baseline in the VES-13 >3 group (5.6 for VES-13 >3 vs -0.5 for VES-13 <3, p=0.002). SFWB changes from baseline did not differ between groups.

In adults >65, 83 (17%) had a VES-13 >3, which was associated with a significant improvement from baseline PWB (1.3, 1.5 for VES-13 >3 vs. 0.1, -0.1 for VES-13 <3), FWB (3.3, 2.2 for VES-13 >3 vs. 0.5, 0.1 for VES-13 <3), and total FACT-G score (5.2, 3.4 for VES-13 >3 vs. 1.0, -0.4 for VES-13 <3) when compared to VES-13 <3 at years 1 and 2 (all p<0.05). SFWB and EWB changes from baseline did not differ between groups.

While there was improvement from baseline PWB and FWB in the VES-13 >3 group, QOL scores across all subscales remained below the VES-13 <3 group in the study period for both age groups. Statistical significance was maintained in models adjusted for baseline characteristics, including initial treatment strategy (observation, systemic, vs local) for both age groups.

Conclusion: Although the vulnerable group reported worse QOL throughout the study period compared to the non-vulnerable group, survivors in the vulnerable group saw greater improvement in their physical and functional well-being at 1- and 2-years post-diagnosis. Additional analyses are underway to identify drivers of improvement in physical and functional well-being in vulnerable adults diagnosed with iNHL.

Tsang:Novartis: Other: Advisory Board; AVEO: Other: Prior holder of stock options in a privately-held company; AstraZeneca: Other: Advisory Board; Poseida Therapeutics: Current holder of stock options in a privately-held company. Casulo:Bristol Myers Squibb: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Gilead Sciences, Secura Bio: Research Funding; AbbVie: Consultancy, Honoraria; Genmab: Research Funding; Verastem: Research Funding. Rosenthal:RMEI, Curio Science, Targeted Oncology, OncLiveU: Other: Educational Workshop Speaker Role. Chihara:SymBio pharmaceutical: Honoraria; MorPhosys: Research Funding; BMS: Research Funding; Ono pharmaceutical: Research Funding; Genmab: Research Funding; BeiGene: Honoraria. Maurer:AstraZeneca: Membership on an entity's Board of Directors or advisory committees; GenMab: Research Funding; Roche/Genentech: Research Funding; BMS: Consultancy, Research Funding. Feldman:Seattle Genetics: Research Funding; Zeno Pharmaceuticals: Patents & Royalties. Major:Roche/Genentech: Consultancy; Incyte: Research Funding. Hilal:BeiGene: Consultancy, Research Funding. Wang:Eli Lilly, LOXO Oncology, TG Therapeutics, Incyte, InnoCare, Kite, Jansen, BeiGene, AstraZeneca, Genmab, AbbVie: Other: Advisory Board; InnoCare, AbbVie: Consultancy; Incyte, InnoCare, LOXO Oncology, Eli Lilly, MorphoSys, Novartis, Genentech, Genmab, AbbVie, BeiGene, Merck: Research Funding; Kite: Honoraria. Parikh:AstraZeneca: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Merck: Consultancy, Research Funding; AbbVie: Consultancy; Amgen: Consultancy; BeiGene: Consultancy; Kite: Consultancy; MingSight: Consultancy; Novalgen Limited: Consultancy; Pharmacyclics: Consultancy. Munoz:Targeted Oncology, OncView, Curio, Genzyme, and Physicians' Education Resource: Honoraria; Bayer, Gilead/Kite, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium, Novartis, BeiGene: Research Funding; Pharmacyclics/Abbvie, Bayer, Gilead/Kite, Beigene, Pfizer, Janssen, Celgene/BMS, Kyowa, Alexion, Fosunkite, Seattle Genetics, Karyopharm, Aurobindo, Verastem, Genmab, Genzyme, Genentech/Roche, ADC Therapeutics, Epizyme, Beigene, Novartis, Morphosys/Incyte: Consultancy. Thanarajasingam:Novartis: Other: Advisory Board (one time - completed, no personal remuneration); SeaGen: Other: Advisory Board (one time - completed, no personal remuneration). Nastoupil:Daiichi Sankyo: Honoraria, Research Funding; Genmab: Honoraria, Research Funding; Denovo Biopharma: Honoraria; Genentech: Honoraria, Research Funding; Incyte Corporation: Honoraria; Merck: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Caribou Biosciences: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Abbvie, BMS, Caribou Biosciences, Genentech, Genmab, Gilead/Kite, Janssen, Incyte, Ipsen, Merck, Novartis, Regeneron, Takeda: Consultancy; Takeda: Consultancy, Honoraria, Research Funding; Gilead Sciences/Kite Pharma: Honoraria, Research Funding; AbbVie: Honoraria; ADC Therapeutics: Honoraria; Regeneron: Consultancy, Honoraria; BMS, Caribou Biosciences, Daiichi Sankyo, Genentech, Genmab, Gilead/Kite, Janssen, Incyte, Ipsen, Merck, Novartis, Takeda: Research Funding; Abbvie, BMS, Caribou Biosciences, Daiichi Sankyo, Genentech, Genmab, Gilead/Kite, Janssen, Incyte, Ipsen, Novartis, Takeda: Honoraria. Nowakowski:Ryvu Therapeutics: Consultancy; Curis: Consultancy, Research Funding; Incyte Corporation: Consultancy; MEI Pharma: Consultancy; Fate Therapeutics: Consultancy; Debiopharm: Consultancy; Genentech: Consultancy; Blueprint Medicines Corporation: Consultancy; Zai Laboratory: Consultancy; Karyopharm Therapeutics: Consultancy; MorphoSys AG: Consultancy, Research Funding; Daiichi Sankyo: Consultancy; Kymera Therapeutics: Consultancy; Celgene Corporation: Consultancy, Research Funding; F. Hoffmann-La Roche Limited: Consultancy; Selvita Inc: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Segen: Consultancy; Constellation Pharmaceuticals: Consultancy; Bantam Pharmaceutical, LLC: Consultancy; AbbVie Inc.: Consultancy; ADC Therapeutics: Consultancy; TG Therapeutics Inc: Consultancy. Cohen:Lilly: Consultancy, Research Funding; Nurix: Research Funding; Kite/Gilead: Consultancy; Hutchmed: Consultancy, Research Funding; Genentech: Research Funding; Janssen: Consultancy; Astra Zeneca: Consultancy, Research Funding; Takeda: Research Funding; Beigene: Consultancy. Habermann:Lilly: Other: Data Monitoring Committee. Strouse:Poseida: Research Funding; Seagen: Research Funding; Pfizer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Research Funding; Bristol Meyer Squibb: Research Funding. Lossos:ADCT: Research Funding; Not specified: Patents & Royalties; University of Miami: Current Employment. Kahl:Novartis: Consultancy; Merck: Consultancy; Genentech: Consultancy; Roche: Consultancy, Research Funding; AbbVie: Consultancy; AstraZeneca: Consultancy, Research Funding; Kite: Consultancy; Lilly: Consultancy; BeiGene: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy; ADCT: Consultancy. Martin:AbbVie, AstraZeneca, Beigene, Daiichi Sankyo, Genentech, Janssen, Merck, Pepromene: Consultancy. Flowers:Pharmacyclics / Janssen: Consultancy; Cellectis: Research Funding; Pfizer: Research Funding; Adaptimmune: Research Funding; Gilead: Consultancy, Research Funding; Morphosys: Research Funding; Burroughs Wellcome Fund: Research Funding; Janssen Pharmaceuticals: Research Funding; TG Therapeutics: Research Funding; Xencor: Research Funding; BeiGene: Consultancy; Takeda: Research Funding; Eastern Cooperative Oncology Group: Research Funding; Seagen: Consultancy; Iovance: Research Funding; Novartis: Research Funding; Acerta: Research Funding; Spectrum: Consultancy; Bayer: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Foresight Diagnostics: Consultancy, Current holder of stock options in a privately-held company; Denovo Biopharma: Consultancy; Nektar: Research Funding; Ziopharm National Cancer Institute: Research Funding; Kite: Research Funding; Guardant: Research Funding; Pharmacyclics: Research Funding; Allogene: Research Funding; Karyopharm: Consultancy; Sanofi: Research Funding; N-Power Medicine: Consultancy, Current holder of stock options in a privately-held company; 4D: Research Funding; Amgen: Research Funding; BostonGene: Research Funding; Genmab: Consultancy; Genentech/Roche: Consultancy, Research Funding; Cancer Prevention and Research Institute of Texas: CPRIT Scholar in Cancer Research: Research Funding; EMD Serono: Research Funding; AstraZeneca: Consultancy; Bio Ascend: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy, Research Funding. Cerhan:Genentech: Research Funding; BMS: Research Funding; Protagonist Therapeutics: Other: SMC; GenMab: Research Funding.