Beyond approval: Lymphoma drugs and real-world representation (2015–2025) Free

Clinical trial generalizability remains an unmet goal in oncology clinical research. Generalizability refers to the ability to infer the average treatment effect from a sample to the entire target population. Issues associated with a lack of data generalizability is particularly evident when evaluating Federal Drug Administration (FDA) drug approvals for hematology and hematologic malignancies in the United States of America (U.S.) The DRIVE ranking score measures the relative racial/ethnic representation of participants in clinical trials, thereby aiming to strengthen the generalizability of clinical research (Birhiray and Birhiray, 2022). To further assess the representativeness of drugs in hematology/oncology from 2015 to 2025, we reviewed the FDA's “Oncology (Cancer)/Hematologic Malignancies Approval Notifications” webpage and assigned a DRIVE score to each drug approved for the treatment of lymphoma. We have previously defined a minimum DRIVE score of 3 (Minority enrollment reaches 41–60% of expected levels based on disease prevalence, with at least two (2) groups† reaching 60% of its proportional target) as the benchmark for clinical excellence and relevance based on racial representation.

Between August 17th, 2015, and July 2nd, 2025, we identified 53 hematological FDA drug approvals and used the DRIVE calculator to evaluate the generalizability for their targeted treatment populations. Each study was examined for the inclusion of demographic data and reporting of the racial/ethnic composition of its participants. Following this review, a DRIVE score ranging from 0(x,*) to 5, lowest to highest proportion of racial/ethnic minority enrollment, respectively, was assigned to each study, with out-of-scope studies excluded from this analysis. Out-of-scope studies are those whose demographics are entirely pediatric, or all testing locations were outside of the U.S.. Demographic information was recorded as it was available at the time of this abstract's submission, based on the National Cancer Institute (NCI) clinical trial results section and related articles.

A total of 6 lymphoma clinical trials met the criteria for clinical trial excellence, revealing an overwhelming lack of generalizability within FDA drug approvals. The list of scores and how many studies received them is as follows: 9 studies received a score of 0x, 1 received a 0, 29 received a 0*, 7 received a 1, 1 received a 2, 4 received a 3, 2 received a 4, and no studies achieved a score of 5.

Our findings reveal that between 2015 and 2025, 6 out of 53 clinical trials associated with FDA approvals met the minimum criteria for clinical trial excellence. These trials are/were: acalabrutinib with bendamustine and rituximab, lisocabragene maraleucel, axicabtagene ciloleucel, mosunetuzumab, asparaginase erwinia chrysanthemi, and tisagenlecleucel. While these drugs have received FDA approval, 88.7% do not accurately represent the intended patient populations. These approvals exacerbate disparities, particularly among minoritized populations, and leave critical gaps in understanding potential adverse reactions, side effects, and efficacy. Historical migration patterns, systemic inequities, and biological factors such as genetic polymorphisms and microbiome diversity all contribute to varied treatment responses among different racial and ethnic groups. However, current trial designs often fail to account for these differences, resulting in regulatory approvals based on non-generalizable data. With this analysis, we aim to highlight to researchers that FDA approval does not automatically indicate safety or efficacy for all patients. There is a need to minimize therapeutic misrepresentation, which we define as the assumption that approved drugs with promising clinical trial data have demonstrated effectiveness across all patient populations. Additionally, a clearer understanding of the DRIVE Score Ranking and its purpose can help researchers identify which drugs are supported by generalizable and transportable data, ultimately guiding more inclusive and equitable clinical research practices. For these reasons, we advocate that only trials meeting the minimum standards for clinical trial excellence should be used for FDA approvals to ensure equitable benefits for all patients.