TOPLINE:

In a phase 2 single-arm trial, an 8-week dose-dense modified Stanford V chemotherapy regimen allowed most evaluable pediatric patients with low-risk Hodgkin lymphoma to avoid radiation therapy. Among 72 evaluable patients, 76.4% achieved a complete response after 8 weeks of chemotherapy and did not require radiotherapy, with 100% overall survival at 5 years.

METHODOLOGY:

• Although combined modality therapy in children with classic Hodgkin lymphoma is associated with 5-year survival rates of more than 95%, treatment-related toxicity can shorten lifespan and cause chronic morbidity. In the current analysis, researchers assessed whether patients could forgo radiotherapy and maintain outcomes.
• Researchers conducted a phase 2, multicenter, single-arm trial that enrolled 85 patients (median age, 14.4 years) with previously untreated stage IA or IIA Hodgkin lymphoma without mediastinal bulk or extranodal extension and with fewer than three involved sites.
• Patients received a modified 8-week Stanford V regimen wherein vinblastine (6 mg/m²) and doxorubicin (25 mg/m²) were administered on days 1 and 15, vincristine (1.4 mg/m²) and bleomycin (5 units/m²) on days 8 and 22, mechlorethamine (6 mg/m²) on day 1, etoposide (120 mg/m²) on day 15, and prednisone (40 mg/m²) every other day.
• Response was assessed with PET and anatomic imaging (CT or MRI). Modified, tailored-field radiotherapy was administered only to sites with partial response or stable disease.
• The primary objective was to increase the complete response rate after 8 weeks of chemotherapy by at least 20% (from 44% to 64%) compared with the rate observed in a previous trial; the secondary outcomes were acute hematologic toxicities, event-free survival (EFS), and overall survival. The median follow-up duration was 6.9 years.

TAKEAWAY:

• In the overall cohort of 85 patients, 5-year EFS was 87.4% and overall survival was 98.7%. Among 72 patients evaluated for the primary objective, 76.4% (55 of 72) achieved complete response at all sites after 8 weeks of chemotherapy and avoided radiotherapy. The 5-year EFS rate was 88.7%, and the overall survival rate was 100.0% among these patients.
• Overall, 16 patients who didn’t achieve a complete response after chemotherapy received tailored involved site radiotherapy (25.5 Gy). In this group, 5-year EFS was 80.7%, and 5-year overall survival was 93.3%.
• In a post hoc analysis of patients with classic Hodgkin lymphoma treated with mechlorethamine only (n = 45), 76.6% achieved complete response, with 5-year EFS of 93.0% and 5-year overall survival of 100%. Substituting cyclophosphamide for mechlorethamine was associated with markedly worse outcomes: 5-year EFS was 67.3% vs 92.2% with cyclophosphamide vs mechlorethamine (P = .003).
• Grade 3-4 neutropenia was the most common acute toxicity, affecting 47% of patients, followed by lymphopenia (24.7%) and anemia (8.2%); late toxicities were infrequent and mostly mild (hypothyroidism in 6.8% of patients and pulmonary function abnormalities in 13.5% of patients).

IN PRACTICE:

A dose-dense modified Stanford V regimen “reduced the proportion of pediatric patients with low-risk [Hodgkin lymphoma] requiring [radiotherapy],” the study authors wrote, but also emphasized that “results should be interpreted with caution given the modest sample size and historical comparison group.”

This trial “demonstrates that more effective systemic therapy can reduce the need for [radiotherapy] while maintaining excellent outcomes,” said Jaclyn Rosenzweig and Lisa Giulino-Roth, Weill Cornell Medicine, New York City, in an accompanying editorial. “The ideal chemotherapy backbone to achieve this, however, remains an unanswered question.”

SOURCE:

The study, led by Jamie E. Flerlage, MD, University of Rochester Medical Center, Rochester, New York, and Angela M. Feraco, MD, Dana-Faber Cancer Institute, Boston, was published online in Blood, alongside an editorial.

LIMITATIONS:

The study limitations included single-arm design, small sample size, use of a historical comparison group, and inclusion of both classic Hodgkin lymphoma and nodular lymphocyte-predominant Hodgkin lymphoma. Additionally, mechlorethamine is no longer available, limiting direct applicability of the exact regimen.

DISCLOSURES:

The study received support from the National Cancer Institute of the National Institutes of Health and the American Lebanese Syrian Associated Charities. The authors reported having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.