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

Blood. 2021 Jul 1;137(26):3595-3603. doi: 10.1182/blood.2020009806.

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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Anaplastic Lymphoma Kinase* / genetics
  • Anaplastic Lymphoma Kinase* / metabolism
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Brentuximab Vedotin / administration & dosage*
  • Brentuximab Vedotin / adverse effects
  • Child
  • Child, Preschool
  • Disease-Free Survival
  • Female
  • Humans
  • Lymphoma, Large-Cell, Anaplastic* / drug therapy
  • Lymphoma, Large-Cell, Anaplastic* / enzymology
  • Lymphoma, Large-Cell, Anaplastic* / genetics
  • Lymphoma, Large-Cell, Anaplastic* / mortality
  • Male
  • Neoplasm Proteins* / genetics
  • Neoplasm Proteins* / metabolism
  • Survival Rate

Substances

  • Neoplasm Proteins
  • Brentuximab Vedotin
  • ALK protein, human
  • Anaplastic Lymphoma Kinase

Associated data

  • ClinicalTrials.gov/NCT01979536