In a phase II trial reported in the Journal of Clinical Oncology, Burke et al found that dose-adjusted etoposide, doxorubicin, and cyclophosphamide with vincristine and prednisone plus rituximab (DA-EPOCH-R) did not improve event-free survival vs historical controls in children and adolescents with newly diagnosed primary mediastinal large B-cell lymphoma.

As stated by the investigators, “DA-EPOCH-R has been shown to deliver excellent survival for adults with [primary mediastinal large B-cell lymphoma] without the use of radiotherapy. No international prospective evaluation of this regimen has previously been reported in children and adolescents.”

Study Details

The study, conducted by the European Intergroup for Childhood Non-Hodgkin Lymphoma and the Children’s Oncology Group, enrolled patients aged 6 months to 18 years from sites in nine countries between April 2012 and April 2016. A total of 46 evaluable patients (median age = 15.4 years, interquartile range [IQR] = 14–16 years) received six courses of DA-EPOCH-R with granulocyte colony–stimulating factor and dose escalation of doxorubicin, etoposide, and cyclophosphamide according to pre-established rules. The primary endpoint was event-free survival.

Event-Free Survival

Median follow-up was 59.0 months (IQR = 52.6–69.2 months). Complete remission was achieved in 39 patients (85%). A total of 14 event-free survival events were observed, consisting of 8 disease relapses or progressions (including 3 parenchymal CNS relapses), 4 residual lymphoma, and 2 second malignancies. Event-free survival at 4 years was 69.6% (95% confidence interval [CI] = 55.2%–80.9%); the rate did not differ from the rate of 67% observed in a historical cohort (P = .59).

Data were available to assess adherence to dose-escalation rules for 42 patients. Among 12 who did not receive a stipulated dose escalation in at least one course of treatment, 4-year event-free survival was 58.3% (95% CI = 32.0%–80.7%), compared with 76.7% (95% CI = 59.1%–88.2%) in the remaining 30 patients (P = .15)

Overall survival at 4 years was 84.8% (95% CI = 71.8%–92.4%). Among the seven deaths, six were related to primary mediastinal large B-cell lymphoma and one was due to second malignancy.

Adverse Events

Grade 4 neutropenia occurred in 106 (42%) of 251 courses and grade 4 thrombocytopenia in 8 (3%) of 252 courses. Nonhematologic adverse events of grade ≥ 3 or cardiac adverse events of grade ≥ 2 occurred in 47 (17%) of 276 courses and 30 (65%) of 46 patients (65%). Grade ≥ 2 cardiac events occurred in four patients (9%). The most common adverse event was febrile neutropenia, with 29 episodes occurring during 276 courses (10.5%) in 21 patients (46%). Grade ≥ 3 infection occurred in eight patients (17%). No toxicity-related deaths were reported.

The investigators concluded, “DA-EPOCH-R did not improve the event-free survival compared with a historical control in this first prospective multisite international study of children and adolescents with [primary mediastinal large B-cell lymphoma]. Further studies are required to determine the optimum therapy for children and adolescents with this lymphoma.”

G.A. Amos Burke, MB ChB, PhD, of the Department of Paediatric Haematology, Oncology and Palliative Care, Addenbrooke’s Hospital, Cambridge, UK, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by the Clinical Research Hospital Program of the French Ministry of Health, Enfants Cancers Santé, U.S. National Cancer Institute National Clinical Trials Network, Cancer Research UK, and UK National Institute for Health Research Clinical Research Network. For full disclosures of the study authors, visit ascopubs.org.