Data from Matched Targeted Therapy for Pediatric Patients with Relapsed, Refractory, or High-Risk Leukemias: A Report from the LEAP Consortium
Year: 2023
Type: other
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
Authors: 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 Gennarini, Asmani 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
Institutions: Boston Children's Hospital, Dana-Farber Cancer Institute, Children's Hospital of Philadelphia, Abramson Cancer Center, University of Pennsylvania, Memorial Sloan Kettering Cancer Center, Columbia University Irving Medical Center, Columbia University, University of California, San Francisco, UCSF Helen Diller Family Comprehensive Cancer Center, Seattle Children's Hospital, Emory University, Children's Healthcare of Atlanta, Children's Hospital Colorado, University of Colorado Cancer Center, Children's Hospital of Wisconsin, Medical College of Wisconsin, Sidney Kimmel Comprehensive Cancer Center, Children's Minnesota, University of Chicago, Comer Children's Hospital, Children's Hospital at Montefiore, Rutgers Cancer Institute, Hackensack University Medical Center, Roswell Park Comprehensive Cancer Center, St. Louis Children's Hospital, Washington University in St. Louis, Broad Institute, Harvard University, Oregon Health & Science University, OHSU Knight Cancer Institute, University Hospital Frankfurt, Inserm, Hôpital Saint-Louis, Brigham and Women's Hospital
Language: English
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4362560220