Evaluation of Minimal Residual Disease as a Surrogate for Progression-Free Survival in Hematology Oncology Trials: A Meta-Analytic Review

TL;DR

This meta-analytic review assesses whether minimal residual disease (MRD) can reliably serve as a surrogate endpoint for progression-free survival in hematology oncology trials, potentially enabling earlier drug approvals.

Contribution

It provides a comprehensive evaluation of MRD's surrogacy potential across various hematologic cancers, focusing on its correlation with clinical outcomes.

Findings

MRD shows promising correlation with PFS and OS in certain hematologic cancers.

The study highlights the potential of MRD to accelerate drug approval processes.

Evidence supports further validation of MRD as a surrogate endpoint.

Abstract

Traditional health authority approval for oncology drugs is based on a clinical benefit endpoint, or a valid surrogate. In 1992 the FDA created the Accelerated Approval pathway to allow for earlier approval of therapies in serious conditions with an unmet medical need. This is accomplished typically by granting accelerated approval based on a surrogate endpoint that can be measured earlier than a traditional approval endpoint. Minimal residual disease (MRD) is a sensitive measure of residual cancer cells in hematology oncology after treatment, and is increasingly considered as a secondary or exploratory endpoint due to its prognostic potential for traditional clinical trial endpoints such as progression-free survival (PFS) and overall survival (OS). This work aims to evaluate MRD's surrogacy potential across several hematologic cancer indications while keeping the focus on follicular lymphoma (FL), using data from published studies. We examine individual-level and trial-level correlations extracted from previously published studies to elucidate the potential role of MRD in accelerating the drug approval process in hematology oncology trials.