Beyond maximum grade: advancing the measurement and analysis of adverse events in malignant haematology trials in the modern era.

Abstract

As the therapeutic landscape in haematological malignancies has evolved from traditional chemotherapies to novel biological, targeted, and cellular therapies, adverse event profiles have accordingly shifted with emerging and newly described chronic, cumulative, and delayed symptomatic adverse events. The current standard of toxicity reporting in clinical trials, centred on maximum-grade adverse events, is wholly inadequate for characterising the tolerability of therapies in the modern era. As such, the science of adverse event measurement, analysis, and reporting in clinical trials needs to evolve with our ever-growing repertoire of therapeutics to facilitate more comprehensive and accurate toxicity assessment for treatment decision making. In this first paper in the Adverse Event Reporting Series, a follow-up of a 2018 Lancet Haematology Commission, we review advances in the reporting of newly described adverse events and toxicity domains in haematological malignancies, emerging clinical trial designs to more accurately identify optimal dosing strategies through enhanced adverse event measurement, and novel analytic and visualisation tools to facilitate interpretation of trial adverse event data.