Brentuximab vedotin in combination with chemotherapy for pediatric patients with ALK ⁺ ALCL: results of COG trial ANHL12P1

Abstract

Anaplastic large cell lymphoma (ALCL) is a distinct form of T-cell non-Hodgkin lymphoma which accounts for 10% to 15% of all childhood lymphomas. Lowe and colleagues report on the addition of brentuximab vedotin to standard chemotherapy in unselected stage II to IV newly diagnosed patients, finding minimal additional toxicity and favorable event-free survival without any on-therapy relapse. These data suggest an advance in the management of ALCL.

Key Points

• The addition of brentuximab vedotin was tolerable and prevented relapses, and EFS compares favorably with conventional chemotherapy.

• The study confirmed that minimal disseminated disease detection in peripheral blood was prognostic, with a significant impact on EFS.

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Abstract

Approximately 30% of pediatric patients with anaplastic large cell lymphoma (ALCL) relapse. Although brentuximab vedotin has demonstrated excellent activity in ALCL, it has not been used for newly diagnosed patients. Children’s Oncology Group (COG) trial ANHL12P1 determined the toxicity and efficacy of brentuximab vedotin with chemotherapy in children with newly diagnosed nonlocalized anaplastic large cell lymphoma kinase (ALK) ⁺/CD30 ⁺ ALCL. From 2013 to 2017, 68 children with ALK ⁺ ALCL were enrolled and received brentuximab vedotin. All patients received 5-day prophase, followed by 6 cycles of chemotherapy. Brentuximab vedotin was given on day 1 of each of the 6 cycles. Of the 67 patients eligible for toxicity evaluation, 66 completed all 6 cycles of chemotherapy, resulting in 399 evaluable cycles. There were no toxic deaths, no case of progressive multifocal leukoencephalopathy syndrome, and no case of grade 3 or 4 neuropathy. The 2-year event-free survival (EFS) was 79.1% (95% confidence interval [CI], 67.2-87.1). The 2-year overall survival (OS) was 97.0% (95% CI, 88.1-99.2). Fourteen patients relapsed. Eleven of 14 (79%) relapses occurred within 10 months of diagnosis; only 1 patient (1.5%) relapsed during therapy. Quantitative reverse transcription polymerase chain reaction for NPM-ALK at baseline (minimal disseminated disease) demonstrated prognostic value for EFS ( P = .0004). Overall, the addition of brentuximab vedotin to standard chemotherapy does not add significant toxicity or alter the desired interval between cycles. The addition of brentuximab vedotin prevented relapses during therapy, and the OS and EFS estimates compare favorably with results obtained using conventional chemotherapy. This trial was registered at www.clinicaltrials.gov as #NCT01979536.