Health-Related Quality of Life after Axi-Cel As a Second-Line Therapy in Patients with High-Risk Relapsed/Refractory Large B-Cell Lymphoma Who Are Ineligible for Autologous Stem Cell Transplantation: Results of the Alycante Phase II Trial

Introduction: The ALYCANTE phase II trial, a LYSA study (ClinicalTrials.gov number NCT04531046), aimed to evaluate the investigator-assessed complete metabolic response at 3 months from the axi-cel infusion as a primary endpoint in patients with high-risk relapsed/refractory large B-cell lymphoma who are ineligible for autologous stem cell transplantation (Houot et al, Nature Medicine 2023). This study showed a significant improvement in complete metabolic response rate at 3 months based on historical controls (primary endpoint). However, there is little data on health-related quality of life (HRQoL) in this population of frail patients treated with CAR T-cells. The present study reports the HRQoL results as a secondary endpoint. Methods: HRQoL was assessed using the EORTC QLQ-C30 cancer-specific questionnaire, the QLQ-NHL-HG29 high grade non-Hodgkin lymphoma module, and the EQ-5D-5L generic questionnaire at baseline, immediately before lymphodepletion, and at 1, 3, 6, 12, 24 and 36 months after CAR-T cell infusion. HRQoL scores were reported using mean and 95% confidence interval (95% CI) at baseline and at 3 months after infusion. Proportion of patients with deteriorated, stable and improved HRQoL at 3 months was reported for each HRQoL score. Adjusted mean change in HRQoL level using mixed model for repeated measure (MMRM) was described at each follow-up time up to 12 months and compared to baseline with a 95% CI. Clinically relevant change was defined as a change of at least 10 points for the QLQ-C30 and QLQ-NHL-HG29, 7 points for the EQ-5D-5L visual analogue scale (VAS), and 0.06 points for the EQ-5D-5L utility score. Unadjusted comparisons between ALYCANTE and ZUMA-7 phase III trial (Axi-cel arm) results were done as exploratory analysis at similar timepoints. Three dimensions (EORTC QLQ-C30 global health status, physical functioning and EQ-5D-5L VAS) were prespecified for the MMRM analyses. Results: Among the 62 patients included in the ALYCANTE trial, 61 patients (98%) completed baseline and at least one post-baseline HRQoL evaluation. Patients presented a lower symptomatic level (lower HRQoL score) at 3 months compared to baseline with a clinically significant difference (greater than the clinical threshold of 10 points) for pain (mean = 11.9 [95% CI 5.4;18.4] at 3 months vs 25.1 [95% CI 17.7;32.6] at baseline), emotional impact (mean = 12.9 [95% CI 8.6;17.2] vs 23.8 [95% CI 17.9;29.6]) and worries/fears about health and functioning (mean = 22.1 [95% CI 16.8;27.3] vs 33.0 [95% CI 27.2;38.8]). At 1 month post-infusion, we observed a clinically and statistically significant deterioration (greater than the clinical threshold) in HRQoL for 4/22 dimensions and stable states (i.e. within the pre-defined clinical threshold) for the other 18/22 dimensions compared to baseline. Regarding the three prespecified dimensions, patients presented a significant deterioration for physical functioning (adjusted mean = -14.2 [95% CI -19.7;-8.7]) and stable states for global health status (-5.9 [95% CI -10.3;-1.5]) and VAS (0.4 [95% CI -4.0;4.7]) compared to baseline. At 3 months post-infusion, 45% of patients (N=18) and 73% of patients (N=30) presented a stable global health status and physical functioning, respectively, and 58% of patients (N=22) experienced an improvement in VAS compared to baseline. At 12 months, we observed a clinically and statistically significant improvement in HRQoL for 3/22 dimensions, including VAS (15.4 [95% CI 10.2;20.6]), and stable states in all other dimensions. In the exploratory analyses, baseline HRQoL level was similar between ALYCANTE and ZUMA-7, except for VAS (meanALYCANTE = 63.5 [95% CI 58.7;68.3] vs meanZUMA-7 = 72.4 [95% CI 69.5;75.2], with a difference exceeding the 7 points) in favor of ZUMA-7 patients and utility score (meanALYCANTE = 0.87 [95% CI 0.82;0.92] vs meanZUMA-7 = 0.80 [95% CI 0.77;0.84], with a difference exceeding the 0.06 points) in favor of ALYCANTE patients. Regarding the MMRM analysis for the three prespecified dimensions, similar results were observed over time between ALYCANTE and ZUMA-7. Conclusions: Transplant-ineligible patients with high-risk relapsed/refractory large B-cell lymphoma treated with Axi-cel in second-line experienced an initial deterioration of HRQoL at 1 month after CAR-T cell infusion in a few dimensions, followed by either a return to the baseline score (stability) or an improvement after 3 months.