Results of a phase 3 trial suggest that brentuximab vedotin (Bv) with doxorubicin (A), vincristine (V), etoposide (E), prednisone (P), and cyclophosphamide (C) should be the new standard frontline therapy among youth with high-risk classic Hodgkin lymphoma (cHL). These findings were presented at the 2022 ASCO Annual Meeting.

Bv is an anti-CD30 antibody-drug conjugate that has not been evaluated among the pediatric population.

Patients were eligible for AHOD1331 (ClinicalTrials.gov Identifier: NCT02166463), an open-label, randomized phase 3 trial, if they were 2 to 21 years old and had a new diagnosis of high-risk cHL (stage IIB with bulk [large mediastinal adenopathy or a nonmediastinal aggregate measuring more than 6 cm] or stage IIIB, IVA, or IVB). A total of 587 patients were randomly assigned to receive 5 cycles of Bv-AVE-PC (n=298) or standard of care AVE-PC with bleomycin (ABVE-PC; n=289) followed by radiation therapy when indicated. All patients were evaluated by interim positron emission tomography after the second cycle.


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The Bv-AVE-PC and ABVE-PC cohorts comprised 53.7% and 52.2% male patients; 82.6% and 86.9% were aged 12 to 21 years, 28.2% and 28.7% had stage IVA disease, 31.2% and 32.2% had stage IVB disease, 52.7% and 56.4% had large mediastinal adenopathy, 75.2% and 77.9% had nodular sclerosing histology, and 71.5% and 70.9% had B symptoms, respectively.

At 3 years, the event-free survival (EFS) rate was 92.1% in the Bv-AVE-PC group and 82.5% in the ABVE-PC group (hazard ratio [HR], 0.41; 95% CI, 0.25-0.67; P =.0002).

In stratified analyses, BV-AVE-PC was favored among patients who had stage IIB disease with bulk (HR, 0.09; 95% CI, 0.01-0.69) and stage IIIB disease (HR, 0.07; 95% CI, 0.01-0.56) and those with B symptoms (HR, 0.43; 95% CI, 0.25-0.74) and with bulk (HR, 0.41; 95% CI, 0.23-0.73). Br-AVE-PC was not favored over ABVE-PC among patients with stage IV disease (HR, 0.66; 95% CI, 0.38-1.16).

The cumulative incidence of relapse was lower among the Bv-AVE-PC recipients (7.5% vs 17.1%; P =.0003).

“Relapse continues, at this point, to be the predominant site of failure. What’s interesting to us, not dissimilar to prior studies including Bv, is how the [cumulative incidence of relapse] curves separate, and the relapse rate plateaus around 2 years [for the Bv-AVE-PC treatment arm but does not plateau in the ABVE-PC arm],” noted Sharon M. Castellino, MD, MSc, of the Emory University School of Medicine and Aflac Cancer and Blood Disorders Center in Atlanta, Georgia, who presented the study.

Similar proportions of patients proceeded to receive radiation therapy in the Bv-AVE-PC study arm (52.7%) and ABVE-PC study arm (55.7%; P =.69).

The overall adverse event rate by arm was 73.5% and 68.2%, respectively; these events included fever or neutropenia (30.9% vs 32.5%), sepsis (2.3% vs 4.2%), and chemotherapy-induced peripheral neuropathy(CIPN) of grade 2 and higher (18.8% vs 19.4%) among the Bv and comparator arms, respectively.

“AHOD1331 is the first randomized phase 3 trial of Bv in children and adolescents and shows a remarkable risk reduction in EFS with the addition of Bv to a dose-intensive regimen of AVE-PC. It is a well-tolerated regimen with low rates of sepsis and severe CIPN. We conclude that Bv-AVE-PC presents a new standard for frontline therapy in pediatric high-risk cHL,” said Dr Castellino.

Disclosure: This research was supported in part by Seagen. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

Reference

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 ASCO 2022; June 3-7, 2022. Abstract 7504