Patient-reported outcomes (PROs) with lisocabtagene maraleucel (liso-cel) in patients with third line or later (3L+) R/R MZL from the Phase 2 TRANSCEND FL study

Abstract

Abstract Introduction: The CAR T cell therapy liso-cel showed promising efficacy and safety in patients with 3L+ R/R MZL in TRANSCEND FL (NCT04245839), a global, phase 2, open-label, single-arm, multicohort, pivotal study (Palomba ML, et al. Hematol Oncol 2025). Here, we present corresponding data for PROs. Methods: Adults with R/R MZL after ≥2 prior lines of therapy (3L+), including those previously treated with a combination of an anti-CD20 antibody and alkylating agent, or who had relapsed disease after HSCT, were enrolled. After leukapheresis, lymphodepleting chemotherapy (LDC), and optional bridging therapy, patients received 1 infusion of liso-cel (100×106 CAR+ T cells). Patients completed the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-30 items (EORTC QLQ-C30), Functional Assessment of Cancer Therapy-Lymphoma “Additional Concerns” Subscale (FACT-LymS), and EQ-5D-5L on the following schedule: pretreatment (≤7 days before LDC; baseline); before infusion on day of liso-cel infusion (Day 1); on Days 15 and 29, and Months 2, 3, 6, 9, 12, 18, and 24 after infusion; and at end of study assessment. Results focus on 8 key PRO scales: 6 primary domains from the EORTC QLQ-C30 (global health status/quality of life [QOL], physical functioning, role functioning, cognitive functioning, fatigue, and pain), the FACT-LymS subscale assessing lymphoma-specific symptoms, and the EQ-5D-5L visual analog score (VAS). Unless otherwise stated, analyses were performed in all liso-cel–treated patients with assessments at baseline and ≥1 postbaseline visit. Linear mixed-effects models for repeated measures were used to calculate least squares (LS) mean change from baseline to Month 18 visit, with responses available for ≥30 patients. The proportion of patients with clinically meaningful changes from baseline were summarized using published thresholds for “meaningful within-patient change.” Time to confirmed improvement in PROs was assessed in all PRO-evaluable liso-cel–treated patients who had potential for meaningful within-patient change as assessed by the Kaplan-Meier method. Results: Among 67 liso-cel–treated patients with 3L+ R/R MZL, 60 were evaluable for EORTC QLQ-C30 analysis (median age, 63 years; 57% male; 55% White). Disease subtypes included extranodal (23%), nodal (48%), and splenic (28%) MZL. Assessment completion rates were >80% across visits up to Month 18 visit. At baseline, mean scores across primary EORTC QLQ-C30 domains were comparable to or slightly above general population norms in Europe and the US. LS mean changes from baseline showed an initial deterioration in EORTC QLQ-C30 primary domains between Day 1 and Day 15, followed by improvements between Day 15 and Month 2 in 5 domains (all except cognitive functioning, which remained stable throughout, reflecting consistently higher scores than the mean general population norms in Europe and the US). These improvements were generally maintained or further enhanced beyond Month 3, with mean scores at Month 18 remaining above baseline values. Additionally, 4 primary domains (global health status/QOL, physical functioning, role functioning, and fatigue) exceeded the threshold for clinically meaningful improvement. Patients demonstrated improvement in lymphoma specific symptoms as assessed by FACT-LymS starting at Day 15, reaching clinically meaningful improvement by Month 2 and remaining improved through Month 18. Patients showed improvement in the EQ-5D-5L VAS as early as Day 15 reaching the minimum threshold to be considered clinically meaningful at Month 6 and remaining improved through Month 12. Across all PROs, the majority of patients (58%–94%, depending on domain and visit) experienced either improvement or no change in primary domains from Day 29 onward. Median time to confirmed improvement was within 4 months for EORTC QLQ-C30 domains and FACT-LymS. Conclusions: In TRANSCEND FL, most patients with 3L+ R/R MZL experienced clinically meaningful improvements in PROs after liso-cel treatment, including symptom relief, enhanced functioning, and improved QOL. The study represents one of the biggest efforts to characterize PROs in patients with 3L+ R/R MZL and provides valuable insights into the patient experience following treatment with liso-cel. The PRO results complement the clinical efficacy and safety profile of liso-cel in 3L+ R/R MZL, reinforcing its potential to become standard of care in this setting.