Brentuximab vedotin plus a chemotherapy regimen showed “consistent efficacy” across age groups of children with newly diagnosed high-risk classical Hodgkin lymphoma.
The results of the randomized Children’s Oncology Group phase III trial were presented at the 2023 American Association for Cancer Research Annual Meeting in Orlando, Florida.
Brentuximab vedotin, a CD30-directed antibody-drug conjugate, is approved in children with previously untreated high-risk classical Hodgkin lymphoma and in six adult indications, including classical Hodgkin lymphoma.
Investigators previously incorporated brentuximab vedotin into a standard chemotherapy backbone treatment regimen of doxorubicin, bleomycin, vincristine, etoposide, prednisone, and cyclophosphamide (ABVE-PC) to replace bleomycin and its “expectant toxicity,” according to the study’s authors. Replacing bleomycin with brentuximab vedotin (BV-AVEPC) in the regimen “resulted in a statistically significant improvement in efficacy compared to ABVE-PC” with “comparable” safety, they wrote.
The current study evaluated the exposure-response relationships in 593 patients aged two to 21 years who had previously untreated high-risk classical Hodgkin lymphoma. The patients were randomized to receive at least one cycle of ABVE-PC (n=297) or BV-AVEPC (n=296). Patients in BV-AVEPC arm received 1.8 mg/kg brentuximab vedotin—at a maximum dose of 180 mg—every three weeks for a maximum of five cycles.
The pharmacokinetics evaluation focused on the 26 patients who were younger than 13 years old, as lower brentuximab vedotin exposure was previously reported in patients with lower body weight. Age and body weight subgroup analyses were conducted on the primary efficacy endpoint, event-free survival (EFS). The key secondary efficacy endpoints included early response rate (ERR) and key adverse events of interest, peripheral neuropathy and neutropenia. They evaluated exposure-response relationships in the pharmacokinetics population of patients.
Compared with adults, using body weight dosing provided similar brentuximab vedotin exposure in patients aged 12 to <18 years, who had a median weight of 54 kg, according to the researchers. Numerically lower antibody-drug conjugate exposure (31%) occurred in patients aged two to <12 years due to their lower body weight (median, 21 kg).
However, treatment with BV-AVEPC showed “consistent efficacy” in pediatric patients across age groups, “despite lower exposure” in patients under 12 years old, the study’s authors wrote.
The 36-month EFS rate was 96.2% in patients aged 2 to <12 years receiving BV-AVEPC, while it was 92% in those aged 12 to <18 years. No trends were observed for ERR.
The researchers reported similar peripheral neuropathy rates (grade ≥3, 5.8% vs 6.4%) and neutrophil count decrease (grade ≥3, 53.8% vs 48.6.%) with BV-AVEPC in patients aged <12 years and 12 to <18 years.
There were “no apparent trends” in neutropenia across body weight groups but there was “slightly elevated” peripheral neuropathy in patients with a body weight of ≥70 kg, according to the study’s authors.
“Overall, there was no consistent evidence that [peripheral neuropathy] and neutropenia were exposure or age-driven in this pediatric population,” they wrote.
In children with previously untreated classical Hodgkin lymphoma, BV-AVEPC showed a “favorable risk-benefit profile” and the results “do not indicate a need” for dose adjustment by age or body weight subgroups, the study’s authors concluded.
Zhang Z, Zhang D, Guo W, et al. Exposure-response and age subgroup analyses to support body-weight (BW) dosing of brentuximab vedotin (BV) in newly diagnosed high-risk classical Hodgkin lymphoma (cHL) in children and young adults (aged 2-21 years [y]): a randomized children’s oncology group phase 3 trial (AHOD1331). Abstract 6737. Presented at the American Association for Cancer Research Annual Meeting; April 14-19, 2023; Orlando, Florida.