Data presented at the 2022 ASCO Annual Meeting by Sharon M. Castellino, MD, MSc, Emory University and Children's Healthcare of Atlanta, GA, demonstrated the superior efficacy of brentuximab vedotin plus doxorubicin, vincristine, etoposide, prednisone and cyclophosphamide (AVE-PC) to that of AVE-PC with bleomycin (ABVE-PC) for pediatric patients with previously untreated, high–risk Hodgkin lymphoma (HL).

“Brentuximab vedotin is approved for adults with advanced stage HL but its use has not been established in children or adolescents,” wrote Dr Castellino et al, who conducted a phase 3, open-label trial comparing the safety and efficacy of brentuximab vedotin plus AVE-PC to the standard pediatric dose intensive regimen ABVE-PC.

A total of 587 treatment-naïve patients (median age, 15.6 years) with stages IIB plus bulk, IIIB, IVA, IVB HL from 151 institutions were included in the study between March 2015 to August 2019. Patients were randomized to receive 5 cycles of ABVE-PC or brentuximab vedotin plus AVE-PC every 21 days with granulocyte colony-stimulating factor support.

“Centrally reviewed PET-CT after 2 cycles identified slow responding lesions defined as Deauville score > 3. Involved site radiotherapy (ISRT) was given to bulky mediastinal adenopathy and SRL,” the researchers explained.

The primary end point of the study was 3-year event-free survival (EFS), with events including relapse and/or progression, second malignant neoplasm, or death. Data cutoff was established as December 31, 2021.

The 3-year EFS by intent-to-treat analyses was 82.5% (confidence interval [CI], 77.4 to 86.5) with ABVE-PC and 92.1% (95% CI, 88.4 to 94.7) with brentuximab vedotin plus AVE-PC at a median follow-up of 42.1 months (95% CI, 0.1 to 80.9; hazard ratio, 0.41 (0.25, 0.67); P = .0002).

For both treatment arms the median time to first event was 9.4 months, although their ranges differed (3.6 to 57.8 with ABVE-PC vs 1.3 to 25.8 with brentuximab vedotin plus AVE-PC). The rate of relapse was 17% with ABVE-PC and 7% with brentuximab vedotin plus AVE-PC.

One second malignant neoplasm was observed in each treatment arm—thyroid cancer at 57.8 months and acute myeloid leukemia at 20.3 months. The 3-year overall survival was 98.5% (95% CI, 96.0 to 99.4) and 99.3% (95% CI, 97.3 to 99.8) for ABVE-PC and brentuximab vedotin plus AVE-PC, respectively (P = .38), and slow responding lesion rates identified with PET-CT after 2 cycles were comparable (ABVE-PC: 19% vs brentuximab vedotin plus AVE-PC: 18%; P = .8). Rates of ISRT receipt did not differ between the treatment arms (ABVE-PC: 55.7% vs brentuximab vedotin plus AVE-PC: 52.7%; P = .69).

There were no differences reported in grade 3/4 adverse events, and only 19% of patients had grade >2 neuropathy according to the Balis pediatric neuropathy scale, with no differences observed between the treatment arms (P = .86).

“Brentuximab vedotin with AVE-PC in a dose intensive regimen has superior efficacy to ABVE-PC for pediatric patients with high-risk HL,” concluded the investigators.

“A 59% risk reduction in EFS was achieved with no increase in toxicity and with fewer patients receiving ISRT compared to prior pediatric trials for high-risk HL,” they added.

Source:

Castellino SM, Pei Q, Parsons SK, et al. Brentuximab vedotin and association with event-free survival (EFS) in children with newly diagnosed high-risk Hodgkin lymphoma (HL): A report from the Children's Oncology Group phase 3 study AHOD1331 (NCT 02166463). Presented at: the 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL. Abstract 7504.