End points and Outcomes in Follicular Lymphoma: What should we measure, how, and why?

Abstract

Overall survival (OS) and quality of life (QoL) are clinically relevant outcomes/endpoints during examination of therapies. However, with median OS approaching 20 years for patients with follicular lymphoma (FL), it is often not feasible to use OS as a primary endpoint in clinical studies. While validated tools for assessing QoL in patient with lymphoma exist, QoL data are rarely the sole basis for drug approvals in FL. Therefore, other survival endpoints, surrogates, and intermediate clinical endpoints have all been used to measure outcomes in FL trials. In this review, we discuss the strengths and limitations of these commonly used traditional endpoints in FL trials and examine the current gaps, including delayed availability of results and suboptimal sensitivity in distinguishing difference in therapeutic effects. To help address the gaps identified, well-validated surrogates, such as complete remission 30 months after starting frontline immunochemotherapy (CR30), may be used as the primary or co-primary endpoint in confirmatory randomized trials. Emerging intermediate endpoints like minimal residual disease, may be useful in early phase trials and in guiding accelerated approvals after appropriate validation. As patient preference plays a crucial role in treatment decisions in FL, it is critical to include QoL as an important secondary trial endpoint and to measure non-medical burdens, including time and financial toxicities. Endpoints that are clinically relevant, timely, and patient-centered may identify new drugs that help patients with FL live longer and better lives.