Patient-reported outcomes and quality of life over time in relapsed/refractory diffuse B-cell lymphoma (DLBCL) patients treated with CAR T-cells therapy in clinical practice

Abstract Background In the context of potential lymphoma curability with the improvement of life expectancy after CAR T-cells, the question of the impact on Patient Reported Outcomes (PROs) and Health-Related Quality of Life (HRQoL) is a major emerging question. Although an improved HRQoL in DLBCL patients following CAR T-cell infusion had been reported in clinical trials, knowledges of PROs and HRQoL remain limited in real-life setting, leading some difficulties to integrate HRQoL patient experiences into standard clinical practice. This retrospective study aims to evaluate PROs and HRQoL over time in R/R DLBCL patients treated with commercial CAR T-cells therapy in third line therapy and after with specific time points and different scales. Methods QOLD-CART is a real world study assessing PROs and HRQoL in R/R DLBCL patients in a single French tertiary Hematology Department. CRS and ICANS (grading according to the consensus criteria from the American Society for Transplantation and Cellular Therapy ASCT), > grade 3 cytopenia, infections, use of tocilizumab, corticosteroids and intensive care unit admission were extracted from electronic medical records. To assess all dimensions of HRQoL, 3 distincts validated questionnaires (EORTC QLQC30, Fact-Lym, EQ-5D-5L) were self administered before lymphodepletion chemotherapy (baseline), at 3 and 6 months after CAR T-cells infusion. The median follow-up was calculated using the reverse Kaplan-Meier method. Progression free survival (PFS) was measured from the date of CAR T-cell infusion to the first documented disease progression, relapse or death from any cause. Overall survival (OS) was measured from the date of CAR T-cell infusion to the death from any cause. The Brief Illness Perception questionnaire (BIPQ) and the Beliefs about Medicines questionnaire(BMQ) were also used to evaluate patient's perception of their illness and their medications respectively. The study was approved by the French Data Protection Committee (n°2020-A03525634). Results Fifty-five consecutive R/R DLBCL patients (sex ratio M/F 2.2, median age 65 [21-82] years) infused with tisagenleucleucel (n=16, 29%) or axicabtagene ciloleucel (n=39, 71%) after 2 lines of therapy were included in QOLD CART study from March 2021 to August 2023. With a median follow-up of 19 months [1.37 - 36.9], the 1-year PFS rate was 61% (95%CI, 0,49-0,75) and the 1-year OS was 74% (95%CI, 0,63-0,87) for the 55 included patients. Fifty-five, 45 and 37 HRQoL questionnaire were completed at baseline, month 3 and 6. Comparison with the reference level of the general french population showed a systematic statistically and clinically altered mean score HRQoL at baseline measured by EORTC QLQ-C30Global Health Status (GHS) (56.0 ± 22.6 vs 68.2 ± 20.1, p=0.0004, MID>10), EQ-5D-5L VAS (54.1 ± 21.8 vs 73.4 ± 22.2, p=10-7, MID>8) and FACT-G (67.8 ± 18 vs 80.1 ± 18.1, p=10-5 MID>7). A global improvement of HRQoL at 3 and 6 months was observed with all scales. Mean change was statistically and clinically significant at month 6 for EORTC QLQ-C30 GHS (p=0.027, MID>10), FACT-Lym total score (p=0.033, MID>7), and EQ-5D-5L VAS (p=0.0012, MID>8). HRQoL reached the values of the general population at month 3 with all scales, with non-significant mean score differences of 3.3±5.05 (EORTC QLQ-C30 GHS, p=0.51), 2.9±3.08 (FACT-G score, p=0.35) and 7,1±4.27 (EQ-5D-5L VAS, p=0.11). The univariate analysis reported better HRQoL at baseline in patients with age > 65 ans (p=0.045), ECOG = 0 (p=0.007), without education beyond high school (p=0.04). A lower mean HRQoL was found for patients treated with bridging therapy (p=0.04), or with polypharmacy (taking > 10 daily drugs)(p=0.01). The occurrence of CRS grade 2-4 (31.5%), ICANS (33.3%), severe infection (61.1%) or intensive care hospitalization (18.5%) were associated with HRQoL impairment at M3 and recovery of certain HRQoL domains at 6 months. However fatigue and GH status remain impaired, and need further evaluation. Patients’ perception of the usefulness of treatment on BMQ increased from baseline to M6 (p=0.004) and the number of patients who perceived the disease as very threatening on BIPQ decreased from 20 to 5. Conclusion This real-life study using 3 distinct questionnaires that CAR T-cells therapy showed improvements of PRO, HRQoL and perception of illness and treatments in DLBCL patients. This study demonstrated faisability of HRQoL evaluation in general clinical practices.