Patient-reported outcomes in patients with hematologic malignancies treated with CAR T-cell therapy in Europe

Abstract

Patient-reported outcomes (PROs) give direct insights into the treatment's impact on patient's life and complement clinical outcomes. However, since the advent of chimeric antigen receptor T-cell therapy (CAR-T), PROs have been underreported. Particularly, little is known about long-term health-related quality of life (HRQoL) and dimensions such as mental- and social well-being, working life, and financial burden. Therefore, we evaluated multidimensional PROs in a cross-sectional study among European patients who received CAR-T for hematologic malignancies. Patients completed validated questionnaires (EQ-5D-5L/EORTC-QLQ-C30/PCL-5/modified-iPCQ) and ad hoc items on treatment experiences, unmet care needs, and HRQoL. The survey was available online (January-October 2023) in 7 languages. Outcomes were compared with the European general population, a matched CAR-T-naive cohort with hematologic malignancies and across subgroups, using established thresholds for clinically important differences/problems and regression models. From 10 European countries, 389 patients participated (>1 year post-CAR-T: 56%). Mean EQ-VAS was 73.1 (standard deviation, 18.5). HRQoL was similar or better than reference cohorts, except for role-, social-, and cognitive-functioning. Physical-functioning problems were most frequently reported (41%), particularly by women, older individuals, and those who experienced neurotoxicity. The latter subgroup also reported more cognitive- and social-functioning problems. Anxiety regarding disease recurrence (76%), infections (66%) and long-term side effects (59%) was common. Among working-age patients, 72% could continue paid work after CAR-T. Younger patients (32%) reported more financial difficulties than older patients (9%). This study shows favorable general HRQoL after CAR-T compared with reference cohorts. However, a notable proportion of patients experienced problems in physical-, mental- and social well-being. We identified high-risk subgroups and care needs that should be addressed during follow-up.

Graphical abstract

Figure 1.

EORTC QLQ-C30 mean domain scores (standard deviation) of the European CAR-T patients compared with a matched cohort of European patients with high-grade NHL and the European general population.^, EORTC QLQ-C30 mean domain scores are presented as a bar chart for all subscales (A) and for the functioning subscales also as a spider plot (B) EORTC QLQ-C30 domain scores were measured with the EORTC QLQ-C30 version 3.0 questionnaire. Domain scores range from 0 to 100. For QL and functioning subscales, higher scores indicate better functioning, whereas higher scores in the symptom subscales indicate higher burden. ^aNot matched for age, sex, or country. ^bA threshold for clinically relevant difference in mean domain score for emotional functioning and the summary score was not available; therefore, we used one-third of the SD of the CAR-T cohort mean domain score for emotional functioning and summary score as thresholds.

Figure 2.

Forest plots of the odds ratios with 95% confidence intervals of the multivariable logistic regression models evaluating the impact of different factors on the prevalence of clinically important problems in the functioning subscales (A) and the symptom subscales^a (B).^aStatistical significance testing using multivariable models was not conducted for constipation and appetite loss due to the limited number of events.

Figure 3.

Proportion of patients experiencing anxiety (in orange) at time of filling in the survey regarding disease recurrence/progression (A); long-term AEs (B); getting an infection (C); and getting COVID-19 in particular (D); and impact of this anxiety on their everyday life (in blue).

Figure 4.

Impact of the different CAR-T treatment phases on everyday life and reasons for a substantial impact on everyday life.^aN = 0, N_R = 389; median: 13 to <19 months (IQR, 4 to <7 months - >2 to 3 years); ^bN = 0, N_R = 385^∗; median: 13 to < 19 months (IQR, 4 to <7 months - >2 to 3 years); ^cN = 8, N_R = 381; median: 13 to <19 months (IQR, 4 to <7 months - >2 to 3 years); ^dN = 99, N_R = 282; median: 19 to 24 months (IQR, 13 to <19 months - >2 to 3 years); ^eN = 63, N_R = 219; median: >2 to 3 years (IQR, 13 to <19 months - >2 to 3 years); ^fN = 219. LD CHEMO, lymphodepleting chemotherapy.

Figure 5.

Return to work in the total European CAR-T cohort (A) and the working-age population (B). (A) Return to work in the total European CAR-T cohort. ^aAt time of filling in the survey. ^bA total of n = 33 respondents replied “not yet, but I will do so in the near future (ie, you will start within 3 months with paid work or you are currently applying for paid work)” to the question if they did start/continue paid work after receiving CAR-T therapy. ^cA total of 10 patients initially continued/started paid work after receiving CAR-T therapy but subsequently also stopped doing paid work because of (early) retirement (n = 5) or other reasons (n = 3; relapse, excessive fatigue, started studying again); reason unknown (n = 2). (B) Return to work in the working-age CAR-T population. ^aAt time of filling in the survey. ^bA total of n = 30 respondents replied “not yet, but I will do so in the near future (ie, you will start within 3 months with paid work or you are currently applying for paid work)” to the question if they did start/continue paid work after receiving CAR-T therapy. ^cA total of 6 patients initially continued/started paid work after receiving CAR-T therapy but subsequently also stopped doing paid work because of (early) retirement (n = 1) or other reasons (n = 3; relapse, excessive fatigue, started studying again); reason unknown (n = 2).