Clearer standardized reporting of toxicity outcomes in phase 1 lymphoma trials is required for improved transparency and communication in drug development, according to a study published at the 66th American Society of Hematology (ASH) Annual Meeting and Exposition.
The study found that phase 1 trial abstracts reported toxicity outcomes inconsistently in terms of toxicity rates and grades. Furthermore, the toxicity reports were frequently incomplete and tended to overuse minimizing terms such as “tolerable,” “safe,” “manageable,” and “acceptable.”
“Adequate, complete reporting of toxicity outcomes is paramount,” the researchers, led by Marsali Maclean, MD, of the Department of Clinical Haematology at Austin Health in Melbourne, Australia, wrote. “Despite this, presentation of phase 1 trial toxicity is highly variable, and minimizing language is frequently used, with no criteria for what should be reported or what defines ‘acceptable’ toxicity.”
The study analyzed toxicity results from 326 phase1 lymphoma trial abstracts published at international conferences (147 from ASH, 84 from EHA, 52 from ASCO, and 43 from ICML) between 2022–2024. Most (95%) of the trials enrolled relapsed or refractory disease; 81% studied B-cell non-Hodgkin lymphoma, 27% diffuse large B-cell lymphoma, 8% Hodgkin lymphoma and 11% T-cell lymphoma. The most common investigational products (IP) were small molecule inhibitors (42%), bispecific antibodies (20%), and cellular therapies (12%).
The abstracts were evaluated to determine whether they reported the following outcomes: all-grade adverse events (64%); grade 3 or higher adverse events (63%); both all-grade and grade 3 or higher adverse events (42%); adverse events of special interest (38%); deaths (43%); and serious adverse events (20%).
Cell therapy studies reported all-grade adverse events, grade 3 or higher adverse events, and serious adverse events at lower rates compared with all other investigational products (10% vs 70%, P<0.001; 34% vs 67%, P<0.001; and 3% vs 38%, P<0.001, respectively). However, cell therapy and bispecific antibody studies more frequently specified adverse events of special interest compared with other investigational products (64% vs 24%, P<0.001). The most commonly reported adverse events of special interest were cytokine release syndrome (30%) and immune effector cell-associated neurotoxicity syndrome (22%).
The researchers also found that 87% of abstracts described safety using minimizing terms such as “tolerable,” “safe,” “manageable,” and “acceptable.”
“Minimizing terms were used almost universally, despite often high rates of toxicity, dose discontinuation and even deaths,” the researchers wrote. “Clearer standardized reporting is required for improved transparency and communication in drug development.”
Reference
Maclean M, Waters N, Smith C. Toxicity outcomes in phase 1 lymphoma trials: variable reporting with high use of minimising language in published abstracts at international conferences. Abstract #2267. Presented at the American Society of Hematology Annual Meeting and Exposition; San Diego, California.
