Abstract
Introduction
Incidence of non-Hodgkin lymphoma (NHL) in adolescent and young adults (AYAs) has increased over the last 25 years. Diffuse large B-cell lymphoma (DLBCL), Burkitt lymphoma, anaplastic large cell lymphoma, lymphoblastic lymphoma, and primary mediastinal B-cell lymphoma are the most common subtypes in patients between the ages of 15 and 19; follicular lymphoma has increased incidence in AYAs who are at least 20 years old.1 Additionally, AYAs with non-Hodgkin lymphoma have increased relapse rates and increased mortality compared to both their childhood and adult counterparts.2 Clinical trials of novel agents often exclude subjects under the age of 18. Because of this, we hypothesized that treatment in adult centers may be associated with increased availability of clinical trials studying novel agents in these at-risk patients.
Methods
A keyword search of "Non-Hodgkin Lymphoma" in the database maintained by ClinicalTrials.govwas performed on May 1, 2016. Age groups, sample size, information on the studied agents, and lymphoma subtypes were collected, as well as whether study sites were members of the Children's Oncology Group. Seventeen categories of novel agents were identified; data was collected on any novel agent contained within a trial protocol.
Results
Of the 726 trials in the initial data set, 404 trials were included in our analysis; studies were excluded from the analysis if the study regimen did not contain a novel pharmacologic agent, or if they focused solely on a transplant conditioning regimen. Sixty-one studies (15%) of novel agents were open to enrollment for subjects under the age of 18 (Table 1). Twenty-five (25) of these trials of these utilized cellular therapy (CAR-T cells, donor lymphocytes, and cytotoxic T lymphocytes). Trials of tyrosine kinase inhibitors (7), novel small molecules (7), monoclonal antibodies (5) were the next-most common agents utilized in clinical trials with the remaining agent classes further detailed in Table 2.
Of the 343 trials that were limited to patients who were at least 18 years old, 227 (66%) trials allowed the enrollment of subjects with DLBCL, Burkitt lymphoma, anaplastic large cell lymphoma, lymphoblastic lymphoma, follicular lymphoma, and primary mediastinal B cell lymphoma.
All agent classes were represented in trials open to patients who were at least 18 years old; however, three agent classes were excluded from clinical trials in the under-18 subset: BiTE immunotherapy, PI3K inhibitors, and pleiomorphic pathway modifiers. Additionally, 178 of 343 trials (51%) included in the analysis that excluded patients under 18 years old had at least one study site which was a member of the Children's Oncology Group.
Conclusions
Adolescent and young adult patients with non-Hodgkin lymphoma have higher relapse rates and lower survival rates than both their pediatric and older adult counterparts. The vast majority of trials study novel agents in the NHL subtypes that most commonly affect the adolescent and young adult population. Half of the trials that exclude patients under 18 years old take place at Children's Oncology Group member sites. While this suggests that adolescent and young adult patients treated at Children's Oncology Group member sites may have access to trials studying novel agents, the extent to which AYAs are being enrolled in these trials requires further study.
[1]Hochberg, J., Waxman, I.M., Kelly, K.M., Morris, E. & Cairo, M.S. (2009) Adolescent NHL and Hodgkin lymphoma: state of the science. Br J Haematol, 144, 24-40.
[2] Bleyer A, O'Leary M, Barr R, Ries LAG (eds): Cancer Epidemiology in Older Adolescents and Young Adults 15 to 29 Years of Age, Including SEER Incidence and Survival: 1975-2000. National Cancer Institute, NIH Pub. No. 06-5767. Bethesda, MD 2006.
Table 1 Age Groups in Clinical Trials for Non-Hodgkin Lymphoma. Table 1. Age Groups in Clinical Trials for Non-Hodgkin Lymphoma. Table 2 Clinical trial enrollment and COG availability by agent class Table 2. Clinical trial enrollment and COG availability by agent class
Disclosures
No relevant conflicts of interest to declare.
Childhood, adolescent and young adult non-Hodgkin lymphoma: state of the science
