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


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.

SUBMITTER: Pikman Y 

PROVIDER: S-EPMC8178162 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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

Pikman Yana Y   Tasian Sarah K SK   Sulis Maria Luisa ML   Stevenson Kristen K   Blonquist Traci M TM   Apsel Winger Beth B   Cooper Todd M TM   Pauly Melinda M   Maloney Kelly W KW   Burke Michael J MJ   Brown Patrick A PA   Gossai Nathan N   McNeer Jennifer L JL   Shukla Neerav N NN   Cole Peter D PD   Kahn Justine M JM   Chen Jing J   Barth Matthew J MJ   Magee Jeffrey A JA   Gennarini Lisa L   Adhav Asmani A AA   Clinton Catherine M CM   Ocasio-Martinez Nicole N   Gotti Giacomo G   Li Yuting Y   Lin Shan S   Imamovic Alma A   Tognon Cristina E CE   Patel Tasleema T   Faust Haley L HL   Contreras Cristina F CF   Cremer Anjali A   Cortopassi Wilian A WA   Garrido Ruiz Diego D   Jacobson Matthew P MP   Dharia Neekesh V NV   Su Angela A   Robichaud Amanda L AL   Saur Conway Amy A   Tarlock Katherine K   Stieglitz Elliot E   Place Andrew E AE   Puissant Alexandre A   Hunger Stephen P SP   Kim Annette S AS   Lindeman Neal I NI   Gore Lia L   Janeway Katherine A KA   Silverman Lewis B LB   Tyner Jeffrey W JW   Harris Marian H MH   Loh Mignon L ML   Stegmaier Kimberly K  

Cancer discovery 20210209 6


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  ...[more]

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