Matched targeted therapy for pediatric patients with relapsed, refractory, or high-risk leukemias: A report from the leap consortium

Yana Pikman, Sarah K. Tasian, Maria Luisa Sulis, Kristen Stevenson, Traci M. Blonquist, Beth Apsel Winger, Todd M. Cooper, Melinda Pauly, Kelly W. Maloney, Michael J. Burke, Patrick A. Brown, Nathan Gossai, Jennifer L. McNeer, Neerav N. Shukla, Peter D. Cole, Justine M. Kahn, Jing Chen, Matthew J. Barth, Jeffrey A. Magee, Lisa GennariniAsmani A. Adhav, Catherine M. Clinton, Nicole Ocasio-Martinez, Giacomo Gotti, Yuting Li, Shan Lin, Alma Imamovic, Cristina E. Tognon, Tasleema Patel, Haley L. Faust, Cristina F. Contreras, Anjali Cremer, Wilian A. Cortopassi, Diego Garrido Ruiz, Matthew P. Jacobson, Neekesh V. Dharia, Angela Su, Amanda L. Robichaud, Amy Saur Conway, Katherine Tarlock, Elliot Stieglitz, Andrew E. Place, Alexandre Puissant, Stephen P. Hunger, Annette S. Kim, Neal I. Lindeman, Lia Gore, Katherine A. Janeway, Lewis B. Silverman, Jeffrey W. Tyner, Marian H. Harris, Mignon L. Loh, Kimberly Stegmaier

Research output: Contribution to journalArticlepeer-review


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 sig-nificance, 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. System-atic integration of precision medicine efforts can inform therapy. We report the feasibility of identify-ing targetable mutations in children with leukemia and describe correlative biology studies validating therapeutic hypotheses and novel mutations.

Original languageEnglish (US)
Pages (from-to)1424-1439
Number of pages16
JournalCancer discovery
Issue number6
StatePublished - 2021

ASJC Scopus subject areas

  • Oncology


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