Promising Developments: Trends of Patient-Reported Outcomes in Diffuse Large B Cell Lymphoma Clinical Trials
Authors: Batra Nitya , Sukaina Mahnoor , Mishra Rahul , Kumar Madhan Srinivasan , Harisingani Avi , Deshmukh Sameer , Garg Tulika , Walia Kamalpreet Singh , Ansar Sadia , Kaur Suhana Preet , Khosla Atulya Aman , Jatwani Karan , Chisti Mohammad Muhsin , Faisal Muhammad Salman 
Published: December 2024

Background: The therapeutic landscape for diffuse large B cell lymphoma (DLBCL) is rapidly expanding, with numerous treatment options available, each variably affecting patients' quality of life. Patient-reported outcomes (PROs) offer valuable insights into these impacts, enhancing patient-centered care. Despite their importance, PROs are infrequently and inconsistently reported in clinical trials. We aimed to evaluate trends in the usage of PROs for patients with DLBCL as a measure of endpoints across global clinical trial databases.

Methods: We searched the Clinicaltrials.gov database for phase III and IV trials involving adult DLBCL patients from 1989 to 2024. A comprehensive search was conducted from clinical trial databases from the US, European Union, Australia/New-Zealand, and WHO International Trial Registry. The data extraction included primary and secondary endpoints, PROs, PRO parameters, and clinical trial duration. Descriptive statistics were used to summarize the data.

Results: A total of n=253 trials were reviewed out of which 58.4% studies (n=148) of studies were completed and 24.5% (n=62) are ongoing. Only 11.9% (n=30) of trials included PROs out of which 63.3% (n=19/30) were completed with 17/30 having available publications, and 33.3% (n=11/30) were ongoing. 97% (n=29) reported PROs as one of their secondary outcome measures and 1 study included PROs as their primary outcome measures. Among completed PRO reporting trials with available demographic data, 52.5%(n=2240/4643) were males, and 63.66% (n=779/1218) patients were Caucasian. The International Prognostic Index (IPI) score ranged from 0-2 in 46.75 % (n=2095/4481) and from 3-5 in 36.5% (n=1634/4481) patients. Of published studies, 73.3% (n=11/15) enrolled patients in first-line treatment, 20% (n=3/15) in second-line, and 7% (n=1/15) in third-line. 47% (n=8/17) of the trials investigated chemotherapy, 23.5% (n=2) targeted therapy, 5.8% (n=1) CAR-T and 11.7% (n=2) studied supportive interventions. From 1989-2004 no trials included PROs, between 2005 to 2009 20% (n=6/30) reported PROs, 2010-2014 33.3% (n=10/30), 2015-2019 26.6%(n=8/30) and 20% (n=6/30) in 2020-2024 had PROs as endpoints. 34 different parameters related to quality of life, depression, pain, fatigue, functional status and neuropathy were utilized to measure PROs. European Organisation for Research and Treatment of Cancer Quality of Life Core Questionnaire (EORTC QLQ C30) and Functional Assessment of Cancer Therapy-Lymphoma (FACT-Lym) were most frequently utilized in 30% (n=9) of the studies.

Conclusions: To our knowledge, this is the first study offering valuable insights into the trends of PRO usage in DLBCL from 1989 to 2024. While PROs are increasingly being incorporated as secondary outcome measures in DLBCL clinical trials, their overall usage remains limited. This can possibly be attributed to the significant heterogeneity in measuring PROs by thirty-four different scales as per our reporting. There is a significant unmet need for standardized and validated tools for PROs in DLBCL which can be used for better understanding of patient experience on these novel therapies.