Adolescents With Hodgkin Lymphoma Have Worse Outcomes Than Children

Take-aways:

• Among patients with Hodgkin lymphoma (HL) enrolled in Children’s Oncology Group trials, adolescents over the age of 15 had worse event-free survival (EFS) than children under 15.
• Adolescents were also at a higher risk of adverse events and death compared with children.
• The researchers concluded that prospective studies are needed to examine tumor and host biology, and to evaluate novel therapies for HL across age groups.

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In a retrospective analysis published in The Lancet Haematology, researchers examined survival rates by age in patients with Hodgkin lymphoma (HL) receiving response-adapted therapy on Children’s Oncology Group (COG) trials.

The average 5-year event-free survival (EFS) rate for patients with HL was nearly 85% as of 2018, and overall survival (OS) exceeds 95% in most cases. “Despite continued progress, population-based studies report worse outcomes in patients aged 15-39 years compared with patients in younger and older age groups,” wrote the authors, led by Justine M. Kahn, MD, of Columbia University Irving Medical Center in New York. “Proposed hypotheses for these disparities include age-associated differences in healthcare access, clinical trial enrollment, survivorship care, and the unique psychosocial needs of adolescents.”

To examine age-based disparities in survival, Dr. Kahn and coauthors retrospectively reviewed outcomes in patients who were diagnosed with classical HL between the ages of 1 and 21 years and enrolled in 1 of 3 phase III COG trials in the US and Canada from September 23, 2002 to January 19, 2012. The trials were defined by risk group according to Ann Arbor stage, B-symptoms, and bulk as follows:

• low-risk (AHOD0431; NCT00302003)
• intermediate-risk (AHOD0031; NCT00025259)
• high-risk (AHOD0831; NCT01026220)

The median age of the 1,907 patients included in the analysis was 15.3 years. A total of 196 patients (10.3%) had mixed cellularity histology, while 1,711 (89.7%) had non-mixed cellularity histology.

Primary endpoints included EFS (death, relapse, or subsequent neoplasm) and OS by age (<15 years vs. 15-21 years). EFS was measured from the date of enrollment to date of first relapse, subsequent malignant neoplasm, or death. OS was measured from enrollment to date of death.

Median follow-up was 7.4 years. Patients age 15 or older had a median follow-up of 6.6 years, while the median follow-up for younger patients was 8.2 years. The pooled 5-year EFS and OS rates across all age groups were 83% and 97%, respectively.

An unadjusted analysis found significantly worse 5-year EFS among older patients compared with younger patients (80% vs. 86%; hazard ratio [HR], 1.38; 95% CI 1.11-1.71; P = .0038). Additionally, 5-year OS was significantly worse in older patients versus younger (96% vs. 99%; HR, 2.50; 95% CI 1.41-4.45; P = .0012). Associations between age and survival remained significant across multivariable models.

Overall, patients age 15 or older also had an increased risk of experiencing an event and increased risk of death, compared with younger patients. A total of 340 on-study events occurred, including 303 relapses, 26 subsequent malignant neoplasms, and 11 deaths. The researchers observed no significant difference in subsequent malignant neoplasm by age (P = .96).

Older patients with non-mixed cellularity histology had a significantly higher risk of experiencing an event than younger patients with the same histology. In patients with mixed cellularity, older patients had significantly worse 5-year EFS, compared with younger patients.

“Findings from this work support the additional hypotheses that HL in adolescents might be biologically distinct from similar histopathological entities in children and that differences in drug exposure, chemotherapy sensitivity, or salvage treatment options might also be involved,” the authors wrote.

Disclosures: This research was supported by the National Institutes of Health, St. Baldrick’s Foundation, and the Lymphoma Research Foundation. The study authors reported no relevant conflicts of interest.

Reference

Kahn JM, Pei Q, Friedman DL, et al. Survival by age in paediatric and adolescent patients with Hodgkin lymphoma: a retrospective pooled analysis of children’s oncology group trials. Lancet Haematol. 2022;9(1):e49-e57.