The clinical trials landscape in follicular lymphoma: A systematic review.

Abstract

e23016 Background: Follicular lymphoma (FL) is an incurable B-cell lymphoma, with advances in therapy leading to a median overall survival (OS) exceeding fifteen years. However, prolonged survival presents challenges in clinical trial design, particularly in endpoints that meaningfully capture OS. Notably, progression-free survival (PFS), a commonly used surrogate, has shown only a weak association with OS in FL. To ensure clinical trials address both longevity and well-being, it is crucial to incorporate endpoints that reflect patients' ability to live longer, healthier lives. This systematic review evaluates ongoing randomized trials in FL, focusing on the integration of QoL and survival endpoints. Methods: A systematic review was conducted on ongoing Phase III FL clinical trials registered on ClinicalTrials.gov. Key data extracted include primary and secondary endpoints and QoL measures. Trials were categorized based on investigational product, and treatment duration. Results: A total of 28 trials were identified, with PFS as the most common primary endpoint (79% of trials), followed by response rates, including ORR and CR (18%). Alternative surrogate survival endpoints, including progression-of-disease within 24 months (POD24), complete response at 30 months (CR30), and minimal residual disease (MRD) was included as an endpoint in 4%, 14%, and 7% of trials respectively. QoL measures were incorporated in 50% of trials. Trials were evenly distributed between first-line (50%) and relapsed/refractory (50%) treatment settings. The most frequently investigated therapeutic category was bispecific antibodies (32%), followed by monoclonal antibodies (21%) and chimeric antigen receptor (CAR) T-cell therapy (18%). Treatment duration was time-limited in 85.7% of trials, while 14.3% involved indefinite treatment plans. Conclusions: Current FL clinical trials exhibit variability in endpoint selection, with PFS frequently used as the primary endpoint despite its weak association with OS. Surrogate survival outcomes such as CR30, POD24, and MRD status remain of uncertain value in FL and continue to be explored. QoL measures are included in 50% of trials, highlighting opportunities for further improvement in addressing patient-centered outcomes. The emergence of CAR T-cell therapy and bispecific antibodies holds promise for further improving OS in FL, underscoring the need for ongoing research into validated surrogates and QoL to guide treatment decisions effectively. Summary of trial characteristics. Variable Trials, n (%) Treatment Status First-line 14 (50) Relapsed/Refractory 14 (50) Primary endpoint OS 1 (3.57) PFS 22 (78.6) Response rates 5 (17.9) Secondary endpoints POD24 1 (3.57) CR30 4 (14.3) MRD 2 (7.14) Quality of life data Collected 14 (50)