Patient-Reported Outcomes after Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Patients with Relapsed/Refractory Large B-Cell Lymphomas

Introduction: Chimeric antigen receptor T-cell (CAR-T) therapy has shown clinical efficacy in refractory and relapsed large B-cell lymphomas, but is associated with serious acute toxicities such as cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). As part of a larger study evaluating baseline biomarkers in prospective patients receiving CAR-T therapy at the Juravinski Hospital and Cancer Centre, we are reporting preliminary data on patient-reported health-related quality of life (HRQoL). Objective: To measure longitudinal HRQoL in patients receiving CAR-T therapy. We expected HRQoL to worsen in the first 30 days, but improve long term.

Methods: A prospective cohort observational study was conducted. Patients with relapsed or refractory large B-cell lymphoma, who were eligible for CAR-T therapy, tisagenlecleucel, were consecutively approached to participate. Demographic data and disease characteristics were collected. Patients received lymphodepleting chemotherapy on days -5 to -3. CAR-T cells were infused on Day 0. CRS and ICANS were assessed using ASTCT criteria. HRQoL was measured using FACT-Lym (Hlubocky et al., Leuk. Lymphoma 2013); a validated 42-item questionnaire answered by the patient on a 5-point Likert scale on days 0 (baseline), day 30, and months 3, 6 and 12. FACT-Lym includes FACT-G (physical, social, emotional and functional well-being domains), plus a lymphoma specific subscale (Lym-S). A score of 0 represents worst HRQoL and higher scores indicate an improvement (score range, 0-168). FACT-Lym Trial Outcome Index (TOI) is a combination of physical and functional well-being and Lym-S. Minimal important differences have been estimated using anchor (performance status and disease progression) and distribution methods for FACT-Lym (Carter et al., Blood 2008).

Results: Among 34 patients registered to the study between January 2020 and June 2021, two did not receive their infusion due to progressive disease. Baseline demographics and disease characteristics are described in Table 1. Twenty-one (21/32, 65.7%) patients required bridging therapy prior to CAR-T infusion. Of the 32 patients who received CAR-T infusion, 22 (68.8%) received an outpatient CAR-T infusion; 18/22 (81.8%) were admitted to hospital. 26/32 (81.2%) developed any grade CRS; 6/32 (18.8%) developed grade 3 or 4 CRS. 6/32 (18.8%) developed grade 1 or 2 ICANS and no one developed grade 3 or 4 ICANS. Ten patients died and one withdrew. The remaining 23 patients were followed for one year. Ethics approval for the FACT-Lym questionnaire administration was pending when the first four patients were recruited. Of the 28 patients approached to complete the FACT-lym questionnaire, 26 (92.9%) completed a baseline and at least one follow-up. Fifteen (15/26, 57.7%) completed the 12-month questionnaire. Two remain on study protocol. Attrition was due to death in six patients, two were unknown, and one was due to withdrawal. The median (IQR) FACT-Lym score at baseline was 129 (106, 146), then worsened at day 30, 117.5 (97, 142), and unexpectedly did not improve beyond baseline by month 3, 128 (108, 156). Scores improved by month 6, 136 (114, 154) and month 12, 141.5 (100, 158). Figure 1 illustrates median change from baseline for FACT-Lym total scores and domains. Median change in FACT-Lym total scores at month 12 and FACT-TOI score at months 6 and 12 surpassed a minimal important difference.

Conclusions: After initial worsening of HRQoL in patients who received CAR-T therapy, improvements were seen at 6 and 12 months. Future analyses will explore associations between HRQoL and baseline markers, toxicity and treatment response. These results will help enrich our understanding of the patient CAR-T experience and aid in complex and shared decision-making.

Balitsky:BMS: Consultancy, Honoraria; Novartis: Honoraria. Pond:Takeda: Honoraria; Merck, Astra-Zeneca, Profound Medical: Consultancy; Roche Canada: Current Employment, Other: Family member currently employed; Roche Ltd.: Other: Family member owns stock. Foley:Novartis: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; BMS: Consultancy, Honoraria, Speakers Bureau.