Health-related quality of life (HRQoL) in patients with relapsed/refractory follicular lymphoma treated with epcoritamab in combination with rituximab plus lenalidomide (E+R2): Primary results of the EPCORE FL-1 trial

Abstract

Abstract Introduction: Relapsed/refractory follicular lymphoma (R/R FL) is an indolent disease characterized by multiple relapses, with some patients experiencing more progressive disease and poor prognosis. Standard of care treatments are chemotherapy-based, which have shown to cause deterioration in quality of life (QoL). While R2 is the only chemotherapy-free option for R/R FL, there is an unmet need for novel treatments that offer improved efficacy while enabling patients to preserve their QoL. EPCORE FL-1 (NCT05409066) is a randomized, global phase 3 study evaluating the efficacy and safety of 12-month fixed duration E+R2 (E dose of 48 mg) vs R2 in R/R FL patients. The objective of this analysis was to assess the impact of E+R2 vs R2 on the HRQoL using a validated patient-reported outcomes (PRO) instrument. Methods: Patients completed the Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) during treatment, at the end of treatment for any reason, and in post-treatment and survival follow-up. Linear mixed-effect regression models were run for the FACT-Lym lymphoma subscale (LymS), treatment outcome index (TOI), and total score. The model included baseline score, trial stratification factors (disease status, geographic region), treatment arm, visit, and interaction between treatment arm and visit. The lower bounds of minimally important difference (MID) thresholds based on published literature (Carter et al. Blood. 2008;112:2376) defined clinically meaningful within-group changes (LymS, 2.9-5.4; TOI, 5.5-11; total, 6.5-11.2). Observed mean changes were measured throughout treatment for individual items that assessed the extent to which patients were bothered by treatment-related side effects using the FACT-Lym item GP5 (“I am bothered by side effects of treatment”) and six lymphoma symptoms (ie, fever, night sweats, body pain, weight loss, lack of energy, and tiring easily). Results: In this analysis (data cutoff Jan 10, 2025), patients were randomized 1:1 to receive E+R2 (N=243) or R2 alone (N=245). Complete response was achieved in 75% of patients treated with E+R2 compared with 43% with R2. Grade 3/4 adverse events were reported in 88% compared with 62%. Completion rates were high for all questionnaires at baseline/C1D1 (>87%) and were over 75% for most on-treatment visits (C2D1-C12D1) across both treatment arms. Baseline scores (mean [SD]) for the FACT-Lym LymS, TOI, and total scores were similar between treatment groups: 46.8 (8.02), 88.7 (14.87), 128.2 (19.97) for E+R2 and 46.1 (8.45), 86.5 (16.24), 125.2 (21.52) for R2, respectively. These scores were greater than 75% of the total range, demonstrating relatively low symptom burden and good QoL at baseline. The linear mixed-effect model results for scores which included functional domains (ie, total score and TOI) showed a small decrease in the first few treatment cycles (C2-C4) for those in E+R2 compared with R2 (with highest mean difference at C2D1 of -2.89 [95% CI: -5.93, 0.15] and -2.71 [95% CI: -5.06, -0.36], respectively), that recovered by C5D1. For total score and TOI, the mean difference at C12D1 was 0.20 (95% CI: -4.18, 4.58) and -0.46 (95% CI: -3.81, 2.88), respectively. The MID threshold for clinically meaningful difference in scores was not met at any time point for either arm. Similar results were also reported in the GP5 where patients reported slightly more bothersome effects from treatment-related side effects for E+R2 in the early treatment cycles; however, scores returned to baseline and were similar to R2 throughout the rest of treatment duration. For the LymS, a disease symptom score, the mean change from baseline at C12D1 for E+R2 was 2.14 (95% CI: 0.92, 3.35) vs R2 of 1.70 (95% CI: 0.34, 3.05), with a mean difference of 0.44 (95% CI: -1.25, 2.13). For the LymS score and the individual items related to lymphoma symptoms, both treatment arms showed no worsening of symptoms throughout treatment.Conclusions: In the EPCORE FL-1 study, patients with R/R FL had relatively low symptom burden and high QoL at baseline. Despite the higher Grade 3/4 adverse events, patients treated with E+R2 maintained their high QoL compared with those treated with R2 alone, complementing the improved efficacy benefits observed in the trial. These data show that the E+R2 regimen has the potential to be a best-in-class, novel chemotherapy-free standard of care in R/R FL and is associated with a manageable safety profile and maintains QoL.