Medical College of Wisconsin
CTSICores SearchResearch InformaticsREDCap

Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium. Cancer Discov 2021 Jun;11(6):1424-1439

Date

02/11/2021

Pubmed ID

33563661

Pubmed Central ID

PMC8178162

DOI

10.1158/2159-8290.CD-20-0564

Scopus ID

2-s2.0-85107440371   8 Citations

Abstract

Despite a remarkable increase in the genomic profiling of cancer, integration of genomic discoveries into clinical care has lagged behind. We report the feasibility of rapid identification of targetable mutations in 153 pediatric patients with relapsed/refractory or high-risk leukemias enrolled on a prospective clinical trial conducted by the LEAP Consortium. Eighteen percent of patients had a high confidence Tier 1 or 2 recommendation. We describe clinical responses in the 14% of patients with relapsed/refractory leukemia who received the matched targeted therapy. Further, in order to inform future targeted therapy for patients, we validated variants of uncertain significance, performed ex vivo drug-sensitivity testing in patient leukemia samples, and identified new combinations of targeted therapies in cell lines and patient-derived xenograft models. These data and our collaborative approach should inform the design of future precision medicine trials. SIGNIFICANCE: Patients with relapsed/refractory leukemias face limited treatment options. Systematic integration of precision medicine efforts can inform therapy. We report the feasibility of identifying targetable mutations in children with leukemia and describe correlative biology studies validating therapeutic hypotheses and novel mutations.See related commentary by Bornhauser and Bourquin, p. 1322.This article is highlighted in the In This Issue feature, p. 1307.

Author List

Pikman Y, Tasian SK, Sulis ML, Stevenson K, Blonquist TM, Apsel Winger B, Cooper TM, Pauly M, Maloney KW, Burke MJ, Brown PA, Gossai N, McNeer JL, Shukla NN, Cole PD, Kahn JM, Chen J, Barth MJ, Magee JA, Gennarini L, Adhav AA, Clinton CM, Ocasio-Martinez N, Gotti G, Li Y, Lin S, Imamovic A, Tognon CE, Patel T, Faust HL, Contreras CF, Cremer A, Cortopassi WA, Garrido Ruiz D, Jacobson MP, Dharia NV, Su A, Robichaud AL, Saur Conway A, Tarlock K, Stieglitz E, Place AE, Puissant A, Hunger SP, Kim AS, Lindeman NI, Gore L, Janeway KA, Silverman LB, Tyner JW, Harris MH, Loh ML, Stegmaier K

Author

Michael James Burke MD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Biomarkers, Tumor
Child
Cohort Studies
Disease Progression
Feasibility Studies
Female
Humans
Leukemia
Male
Molecular Targeted Therapy
Neoplasm Recurrence, Local
Prospective Studies
United States