In a study reported in the Journal of Clinical Oncology, Metzger et al found that the integration of brentuximab vedotin into front-line treatment of pediatric patients with high-risk classical Hodgkin lymphoma resulted in avoidance of radiotherapy in many patients, as well as high rates of event-free and overall survival.

As stated by the investigators, “Brentuximab vedotin, an effective anti-CD30 antibody-drug conjugate approved for use in adults with [classical] Hodgkin lymphoma, was introduced in this front-line trial to reduce prescribed radiation in children and adolescents with [classical] Hodgkin lymphoma.”

Study Details

The U.S.-based multicenter trial enrolled 77 patients aged 6 to 19 years with stage IIB, IIIB, or IV disease between August 2013 and July 2018. Brentuximab vedotin (A) replaced vincristine in the front-line regimen of OEPA (vincristine, etoposide, prednisone, and doxorubicin; AEPA with replacement) and COPDac (cyclophosphamide, vincristine, prednisone, and dacarbazine; CAPDac with replacement). Patients received two cycles of AEPA and four cycles of CAPDac. Residual node radiotherapy (25.5 Gy) was administered at the end of chemotherapy only to nodal sites without complete response at early response assessment after two cycles of therapy. The primary outcome measures were safety and efficacy (complete remission at early response assessment) and 3-year event-free and overall survival.

Key Findings

Among the 77 patients, 27 (35%) achieved complete remission at early response assessment and received no radiotherapy.

Patients who were irradiated received radiation to individual residual nodal tissue. Of 50 patients prescribed radiation, 37 (74%) achieved a metabolic complete response at all sites in the absence of an anatomic complete response at a minimum of one site, and 13 (36%) had no anatomic or metabolic complete response at any sites.

At a median follow-up of 3.4 years, 3-year event-free survival was 97.4% and 3-year overall survival was 98.7%.

One irradiated patient who had disease progression at the end of study therapy received salvage therapy and remained disease-free at 6 years as of last follow-up.

One unexpected death—due to ventricular tachycardia during chemotherapy—occurred in an otherwise healthy patient with stage IVB disease who had not achieved complete response at early response assessment.

Toxicity consisted mostly of low-grade nausea, vomiting, and constipation. The most common adverse events were hematologic, particularly during the first two cycles. Platelet transfusion was required in two patients (3%); red blood cell transfusion was required in 13 (17%); and 19 (25%) received filgrastim during the first cycle (n = 8), second cycle (n = 7), or both (n = 3) cycles. Grade 3 neuropathy occurred in three patients (4%).

The investigators concluded, “The integration of brentuximab vedotin in the front-line treatment of pediatric high-risk Hodgkin lymphoma is highly tolerable, facilitated significant reduction in radiation exposure, and yielded excellent outcomes.”

Monika L. Metzger, MD, MS, of St. Jude Children’s Research Hospital, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was sponsored by Seattle Genetics and supported by the National Cancer Institute. For full disclosures of the study authors, visit ascopubs.org.