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Cancer Discov DOI:10.1158/2159-8290.CD-20-0564

Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory or High-risk Leukemias: A Report from the LEAP Consortium.

Publication TypeJournal Article
Year of Publication2021
AuthorsPikman, Y, Tasian, SK, Sulis, MLuisa, Stevenson, K, Blonquist, TM, Winger, BApsel, 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, Ruiz, DGarrido, Jacobson, MP, Dharia, NV, Su, A, Robichaud, AL, Conway, ASaur, 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
JournalCancer Discov
Date Published2021 Feb 09

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 (VUS), 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.


Alternate JournalCancer Discov
PubMed ID33563661
Grant ListU01 CA232486 / CA / NCI NIH HHS / United States