Analyzing Rates of Exclusion Among Patients Living with HIV in U.S.-Based Non-Hodgkin Lymphoma Clinical Trials from 2014-2024

Introduction: Human Immunodeficiency Virus (HIV) is a major risk factor for and associated with various aggressive non-Hodgkin B-cell lymphomas (NHL) with an increased relative risk of up to 200-fold among persons living with HIV (PLWH) compared to the general population. Despite this, PLWH are often excluded from clinical trials given concern for drug-drug interactions with anti-retroviral therapy (ART) and immunosuppression. In 2017, the National Comprehensive Care Network (NCCN), the National Cancer Institute (NCI), and the American Society of Clinical Oncology (ASCO)-HIV Working Group advocated for the inclusion of PLWH in all clinical trials. We previously estimated that PLWH were included in approximately one-third of lymphoma-related trials prior to 2018. Herein we analyze the inclusion of PLWH in NHL-related clinical trials after the initial ASCO-HIV Working Group recommendations.

Methods: We identified all U.S.-based clinical trials with the keyword “lymphoma” with start dates between 1/1/2014-4/1/2025 using the publicly available National Institute of Health Clinic Trial Database (https://www.clinicaltrials.gov/). We extracted data including clinical trial number, study title, study status, conditions treated, sponsor, collaborators, phase, enrollment number, funder type (i.e., NIH, Industry, or other), start date, time frame (pre-2018 versus post-2018), and CAR-T related study (i.e., yes or no). Each study was individually reviewed and all studies which enrolled adult patients with B-cell NHL subtypes were included in this analysis. We characterized all excluded studies (i.e. pediatric, transplant, solid tumor, non-NHL lymphoma, etc.). Studies that did not specifically delineate whether PLWH were excluded were labeled as being inclusive. Univariate and multivariate analyses were conducted using R software. Purposeful selection of univariate variables with P<0.20 were included in a multivariate regression model.

Results: 1,346 clinical trials were captured during the initial search, of which 58% (n=784) met criteria for inclusion in this analysis. PLWH were potentially eligible to participate in 48% of included studies (n=373). Common reasons for exclusion included leukemia-related (n=219, 36%), transplant-related (n=148, 26%), T-cell lymphoma (n=81, 14%), and pediatric-related trials (n=26, 5%). Most studies were actively recruiting (n=377, 48%) or completed (n=180, 23%) and strictly funded by industry (n=369, 47%). Few studies were solely funded by the NIH (n=69, 9%). Studies were most commonly in phase 1 (n=303, 39%) or phase 2 (n=245, 31%) and included aggressive subtypes of non-Hodgkin’s lymphoma (n=637, 81%). 380 studies were conducted after 2018; of these 56% (n=211) were inclusive of PLWH in comparison to only 40% (n=162) of studies pre-2018. Study size (p=0.017), start date (p<0.001), funding source (p<0.05), and CAR-T trials (p=0.17) met criteria for inclusion in multivariate analysis. After multivariate adjustment, studies initiated post-2018 (p<0.001), those funded by NIH (p<0.001) and other funding sources (p<0.001) were more likely inclusive of PLWH. In addition, CAR-T trials were more common post-2018 (p<0.001).

Conclusion: Nearly half of all U.S. based B-cell NHL clinical trials now include PLWH. The establishment of the ASCO-HIV Working Group in 2017 and subsequent NCCN guidelines may have contributed to this significant increase, along with advocacy from key stakeholders such as the NCI. Although there has been much research demonstrating the safety and efficacy of cytotoxic chemotherapy among PLWH, given the increased use of immunotherapy and targeted therapies, additional research demonstrating the safety profile of these agents is warranted among PLWH. PLWH have a significantly elevated risk of developing aggressive B-cell NHL; efforts to foster inclusion in clinical trials will better enable access to novel therapies, mitigate health disparities, and help reduce stigma among patients, providers, and researchers.