Abstract P094

Dose-dense chemotherapy enables elimination of radiotherapy for a majority of patients with low-risk pediatric Hodgkin lymphoma: a report on HOD08 from the Pediatric Hodgkin Consortium

PURPOSE: To increase complete response (CR) rates by ≥20% (to a goal of ≥64%) using modified Stanford V chemotherapy (8 weeks) compared to 8 weeks of VAMP (vinblastine, doxorubicin, methotrexate, and prednisone) chemotherapy in children with low-risk Hodgkin lymphoma (HL).

METHODS: HOD08 (NCT00846742) was a Phase II, multicenter, investigator-initiated single-arm trial for patients ≤ 21 years of age with previously untreated stage IA or IIA HL without mediastinal bulk or extranodal disease extension and <3 sites of disease. Patients received a modified Stanford V regimen: two 28-day cycles (8 weeks) of chemotherapy (vinblastine 6 mg/m2 intravenous (IV) on days 1 and 15, doxorubicin 25 mg/m2 IV on days 1 and 15, vincristine 1.4 mg/m2 IV on days 8 and 22 (max dose 2 mg), bleomycin 5 units/m2 IV on days 8 and 22, mechlorethamine 6 mg/m2 IV on day 1, etoposide 120 mg/m2 IV on day 15, and prednisone 40 mg/m2/day orally every other day, max dose 60 mg/day). Due to an unanticipated drug shortage, cyclophosphamide was substituted for mechlorethamine in 16 patients. Tailored field radiotherapy (25.5 Gy RT) was administered to sites of disease not in CR (defined as negative PET and ≥75% reduction in the product of 2 perpendicular dimensions by imaging) after 2 cycles of chemotherapy. The primary objective was to increase the CR rate after 8 weeks Stanford V chemotherapy by ≥20% (to a goal of 64%) compared to VAMP-treated patients on HOD99 (NCT00145600). CR rates were compared using Fisher’s exact test and 5-year event-free (EFS) and overall survival (OS) rates calculated via Kaplan-Meier estimation.

RESULTS: Among 85 enrolled patients, 66 (77.6%) achieved a CR and did not receive RT compared to 47 of 88 patients (53.4%) on HOD99 (p=0.001). HOD08 5-year EFS and OS were 87.4% (95% CI 80.4-95.0%) and 98.7% (95% CI 96.2-100%). HOD99 5-year EFS and OS were 88.6% (95% CI 82.2%-95.5%) and 100%. Of 59 patients with classical HL, 45 received mechlorethamine per protocol, while 14 received cyclophosphamide substitution. For mechlorethamine vs. cyclophosphamide treatment, 5-year EFS was 93.0% (95% CI 85.6-100%) vs. 62.3% (95% CI: 40.9-94.9%; p=0.003) and OS 100% vs 92.3% (95% CI: 78.9-100%, p=0.07).

CONCLUSION: The modified 8-week Stanford V regimen successfully increased CR rates and thus reduced the proportion of low-risk pediatric HL patients who received RT compared to HOD99 while maintaining excellent 5-year outcomes. Cyclophosphamide substitution lacked efficacy.