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

Autor:	Pikman Y; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Kimberly_stegmaier@dfci.harvard.edu Yana_pikman@dfci.harvard.edu.; Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts., Tasian SK; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.; Department of Pediatrics and Abramson Cancer Center at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania., Sulis ML; Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Irving Medical Center, New York, New York.; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York., Stevenson K; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Blonquist TM; Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts., Apsel Winger B; Department of Pediatrics, Division of Hematology/Oncology, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California., Cooper TM; Seattle Children's Hospital, Cancer and Blood Disorders Center, Seattle, Washington., Pauly M; Division of Hematology/Oncology, Emory University, Aflac Cancer and Blood Disorders Center, Children's Healthcare of Atlanta, Atlanta, Georgia., Maloney KW; Children's Hospital Colorado, University of Colorado Cancer Center, Aurora, Colorado., Burke MJ; Medical College of Wisconsin, Children's Hospital of Wisconsin, Milwaukee, Wisconsin., Brown PA; Johns Hopkins Kimmel Cancer Center, Baltimore, Maryland., Gossai N; Center for Cancer and Blood Disorders, Children's Minnesota, Minneapolis, Minnesota., McNeer JL; University of Chicago, Comer Children's Hospital, Chicago, Illinois., Shukla NN; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York., Cole PD; Children's Hospital at Montefiore, Bronx, New York.; Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey., Kahn JM; Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Irving Medical Center, New York, New York., Chen J; Division of Pediatric Hematology/Oncology/Stem Cell Transplantation, Columbia University Irving Medical Center, New York, New York.; Children's Cancer Institute, Joseph M. Sanzari Children's Hospital, Hackensack University Medical Center, Hackensack, New Jersey., Barth MJ; Roswell Park Comprehensive Cancer Center, Buffalo, New York., Magee JA; Division of Pediatric Hematology/Oncology, Washington University/St. Louis Children's Hospital, St. Louis, Missouri., Gennarini L; Children's Hospital at Montefiore, Bronx, New York., Adhav AA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Clinton CM; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Ocasio-Martinez N; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Gotti G; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Li Y; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Lin S; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Imamovic A; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts., Tognon CE; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon., Patel T; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Faust HL; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Contreras CF; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania., Cremer A; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; University Hospital Frankfurt, Department of Hematology/Oncology, Frankfurt/Main, Germany., Cortopassi WA; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California., Garrido Ruiz D; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California., Jacobson MP; Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California., Dharia NV; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts., Su A; INSERM UMR 944, IRSL, St Louis Hospital, Paris, France., Robichaud AL; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Saur Conway A; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts., Tarlock K; Seattle Children's Hospital, Cancer and Blood Disorders Center, Seattle, Washington., Stieglitz E; Department of Pediatrics, Division of Hematology/Oncology, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California., Place AE; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts., Puissant A; INSERM UMR 944, IRSL, St Louis Hospital, Paris, France., Hunger SP; Division of Oncology and Center for Childhood Cancer Research, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania.; Department of Pediatrics and Abramson Cancer Center at the Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania., Kim AS; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Lindeman NI; Department of Pathology, Brigham and Women's Hospital, Boston, Massachusetts., Gore L; Children's Hospital Colorado, University of Colorado Cancer Center, Aurora, Colorado., Janeway KA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts., Silverman LB; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.; Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts., Tyner JW; Division of Hematology and Medical Oncology, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon., Harris MH; Department of Pathology, Boston Children's Hospital, Boston, Massachusetts., Loh ML; Department of Pediatrics, Division of Hematology/Oncology, Benioff Children's Hospital and the Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, San Francisco, California., Stegmaier K; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts. Kimberly_stegmaier@dfci.harvard.edu Yana_pikman@dfci.harvard.edu.; Division of Hematology/Oncology, Boston Children's Hospital, Boston, Massachusetts.; Broad Institute of Massachusetts Institute of Technology and Harvard University, Cambridge, Massachusetts.
Jazyk:	angličtina
Zdroj:	Cancer discovery [Cancer Discov] 2021 Jun; Vol. 11 (6), pp. 1424-1439. Date of Electronic Publication: 2021 Feb 09.
DOI:	10.1158/2159-8290.CD-20-0564
Abstrakt:	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 . (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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