Toxicity Under-Reporting in Early-Phase Plasma Cell Dyscrasia Clinical Trial Abstracts

Information regarding treatment toxicity obtained from phase I clinical trials is crucial to inform drug development and patient care, yet no mandatory standards exist for adverse event (AE) reporting within early-phase studies, nor any uniform criteria that define tolerability. Management of plasma cell dyscrasias has changed dramatically in recent years, because of development of novel therapies, which may have unexpected and potentially severe side effects. Outcomes-based reporting is therefore critical to ensure the safety of new treatment regimens in plasma cell dyscrasia (PCD) and all other cancer diagnoses. We sought to assess the current practices in toxicity reporting in phase I PCD abstracts.

Toxicity reporting was analyzed in 250 plasma cell dyscrasia phase I trial abstracts from the American Society of Hematology, ASCO, or the European Hematology Association annual conferences between 2019 and 24.

Significant variation in reporting was seen. Only 70.4% of abstracts reported all-grade toxicity, 80% grade ≥3 toxicity, and 36.8% reported deaths. We observed statistically significant differences in reporting of toxicity grades, deaths, severe AEs, and AEs of special interest according to study sponsor type (industry versus investigator-initiated), timing of analysis (interim versus other), and type of investigational agent. Minimizing language was identified in 77.6% of abstracts. Only 27.3% of these reported all-grade toxicity, of which 66% had an AE rate of ≥90%. Within studies using minimizing language, deaths occurred in up to 15% of patients and treatment discontinuations in up to 28%.

Toxicity reporting in phase I PCD studies demonstrates marked heterogeneity. Minimizing language is used in the majority of abstracts despite significant toxicity. Minimum standards for toxicity reporting in early phase hemato-oncology clinical trial abstracts are urgently required to improve accuracy and transparency.