Health-related quality of life trajectories of patients with aggressive B-cell lymphomas treated with CAR T-cell therapy: Results from a prospective observational study

Abstract Background Chimeric antigen receptor (CAR) T-cell therapy has substantially improved survival for patients with aggressive B-Cell lymphomas and a wealth of efficacy and safety data are now available. However, limited evidence exists regarding health-related quality of life (HRQoL) trajectories of these patients, and this is particularly true for those treated outside controlled clinical trial settings. Objective The primary objective of this analysis was to prospectively assess HRQoL profiles of patients with aggressive B-Cell lymphomas treated with CAR T-Cell therapy up to 12 months. A secondary objective was to explore short term HRQoL improvements by treatment response. Methods This was a multicenter prospective, observational GIMEMA study including patients across 13 centers in Italy. Eligible patients were ≥18 years old with a confirmed diagnosis of aggressive B-cell lymphomas, scheduled to undergo CAR T-cell therapy and with a baseline HRQoL assessment completed. HRQoL and fatigue were assessed with the well-validated EORTC QLQ-C30 and the QLQ-NHL-HG29 and the FACIT-F, respectively. The PROMIS Ability to Participate in Social Roles and the Activities (social function) and the PROMIS Cognitive Function were also used. Mean score changes were estimated using a linear mixed-effects model with repeated measures and analyzed with a growth curve analysis. Mean score trajectories were modeled with fixed effects of the following covariates: age, sex, time of visit and random error to account for the within subject's design. For the purpose of this analysis, we reported data up to 12 months. The “time of visit” variable was considered as continuous, to study if there was a distinguishable temporal trend of the scale over time. A sensitivity analysis was conducted to assess whether HRQoL compliance over time was associated with any baseline characteristics or CRS/ICANS reported at day+10 after infusion. An exploratory analysis was also conducted to quantify the proportion of responders and non-responders reporting early (from 1 month to 3 months post-infusion) HRQoL clinically meaningful improvements. Responders were defined as patients who achieved a complete or partial remission at 3 months. Results Overall, 170 patients were enrolled between June 2022 and February 2024. The median age was 61.1 years and 31.2% were female. HRQoL compliance was 100% and 87% at baseline and 1 months, 75% at 3 and 6 months, and 69% at 9 and 12 months. One-month post-infusion, EORTC QLQ-C30 scales showed statistically and clinically meaningful deteriorations in the following scales: physical (Δ=11.7; p=<.001) and role (Δ=9.4; p=<.001) functioning, fatigue (Δ=12.4; p=<.001). Likewise, also fatigue by the FACIT-F (Δ=4.3; p=<.001) showed a statistically and clinically meaningful deterioration. Interestingly, no decline in cognitive functioning was observed. However, after one-month post infusion, substantial improvements were observed in 13 out of the 15 scales of the EORTC QLQ-C30. Amongst functional aspects, the scale with greater improvement up to 12 months was role functioning (Δ=22.3; p=<.001), while amongst symptoms, fatigue (Δ=19.6; p=<.001) had the greatest improvement over time. Differences over time across scales of the QLQ-NHL-HG29 were not substantial. No associations were found between HRQoL compliance completion over time and baseline characteristics or early (day+10) CRS or ICANS supporting the reliability of our longitudinal model estimates. The percentage of patients with early clinically meaningful improvements in selected HRQoL domains was generally higher in responding patients. For example, clinically meaningful improvements in physical functioning (EORTC QLQ-C30) were observed in 71.8% and 28.6% of responders and non-responders, respectively. Likewise, the percentage of patients with a clinically meaningful improvement in social function (PROMIS) was higher in responders (60%) relative to non-responders (33.3%). Conclusion Substantial HRQoL impairments are observed one-month post CAR T-cell infusion, however, this was not the case for cognitive functioning. However, starting from one-month post infusion, marked changes were observed up to 12 months with clinically meaningful improvements in key health domains, including fatigue. Also, our data suggests that patients who achieve an early response may report greater improvements in HRQoL compared to non-responders.