Brentuximab vedotin shows promise in high-risk pediatric Hodgkin lymphoma
The replacement of vincristine with brentuximab vedotin in standard front-line treatment appeared safe and effective among children and adolescents with high-risk classical Hodgkin lymphoma, according to phase 2 study results.
Results, published in Journal of Clinical Oncology, also showed the use of brentuximab vedotin enabled lower radiation exposure for this group.
“When I started to look for ways to improve the outcome for our high-risk pediatric patients with Hodgkin lymphoma, brentuximab vedotin [Adcetris, Seagen] was soon to be approved for relapsed Hodgkin lymphoma in adults,” Monika L. Metzger, MD, MS, researcher in the department of oncology at St. Jude Children’s Research Hospital, told Healio. “Studies were being designed for the adult population incorporating the treatment into front-line therapy, and we were in a unique position for the first time ever to run a front-line pediatric trial in parallel to adult studies — something that hardly ever happens, as pediatric trials tend to lag behind adult trials while awaiting outcome data. Our hope was to safely eliminate radiation therapy in this pediatric population with an adequate response to the first two cycles of brentuximab vedotin plus etoposide, prednisone and doxorubicin hydrochloride.”
The open-label, single-arm, multicenter trial included 77 patients (median age at diagnosis, 16 years; range, 6-19; 51% female; 65% white) with stage IIB, stage IIIB or stage IV classical Hodgkin lymphoma. Most patients (59%) had stage IV disease and 77% had nodular sclerosing histology.
Researchers replaced vincristine with the anti-CD30 antibody-drug conjugate brentuximab vedotin in a well-established first-line treatment regimen, referred to as OEPA/COPDac, for this patient population. Patients received two cycles of brentuximab vedotin, etoposide, prednisone and doxorubicin hydrochloride, followed by four cycles of cyclophosphamide, brentuximab vedotin, prednisone and dacarbazine. Patients with nodal sites that did not achieve complete response after two cycles of therapy received 25.5 Gy residual node radiation therapy at the conclusion of all chemotherapy.
Primary objectives included evaluation of the safety and efficacy of the brentuximab vedotin combination and 3-year rates of EFS and OS compared with a historical control group that received the Stanford V regimen, which consists of prednisone, nitrogen mustard, doxorubicin, vincristine, etoposide, bleomycin and vinblastine.
Median follow-up was 3.4 years.
Results showed that compared with 17% of historical controls, 35.1% (95% CI, 24.5-46.8) of patients assigned the brentuximab vedotin regimen achieved complete response after two therapy cycles and were spared radiation therapy.
Among the 50 patients who required radiation therapy, 74% achieved a metabolic complete response at all sites. Residual node radiation volumes were small in comparison with historical controls and healthy surrounding tissue was spared, researchers noted.
One patient who received radiation therapy demonstrated disease progression at the end of treatment, but the patient remained disease free more than 6 years after completion of salvage therapy.
Researchers reported 3-year rates of 97.4% for EFS and 98.7% for OS with the brentuximab vedotin regimen, compared with 80.8% and 96.5% among historical controls.
Grade 3 neuropathy occurred among 4% of patients who received brentuximab vedotin, and one unexpected death occurred.
“Brentuximab vedotin is safe and well-tolerated in this pediatric population, and limited radiation fields are adequate to control disease in patients with an inadequate response,” Metzger said. “It is imperative to pursue innovative research in pediatric patients in a safe setting while adult patient data are being gathered at the same time, and that we do not lag behind in lifesaving treatment that harbors less long-term toxicity. My colleague, Jamie E. Flerlage, MD, is taking these findings forward in a new trial that is adapting the response criteria to likely demonstrate that we can irradiate even fewer patients without sacrificing outcome. Radiation is not the enemy — we need to best characterize who will need it in a very targeted approach to prevent relapse.”
For more information:
Monika L. Metzger, MD, MS, can be reached at St. Jude Children’s Research Hospital, 262 Danny Thomas Place, Memphis, TN 38105; email: firstname.lastname@example.org.