American Association for Cancer Research
Browse
- No file added yet -

Supplementary Table S5 from Efficacy of the Allosteric MEK Inhibitor Trametinib in Relapsed and Refractory Juvenile Myelomonocytic Leukemia: a Report from the Children’s Oncology Group

Download (18.9 kB)
journal contribution
posted on 2024-09-04, 07:41 authored by Elliot Stieglitz, Alex G. Lee, Steven P. Angus, Christopher Davis, Donald A. Barkauskas, David Hall, Scott C. Kogan, Julia Meyer, Steven D. Rhodes, Sarah K. Tasian, Xiaoling Xuei, Kevin Shannon, Mignon L. Loh, Elizabeth Fox, Brenda J. Weigel

Genetic and methylation analysis across timepoints.

Funding

National Cancer Institute (NCI)

United States Department of Health and Human Services

Find out more...

St. Baldrick’s Foundation (SBF)

Alex’s Lemonade Stand Foundation for Childhood Cancer (ALSF)

History

ARTICLE ABSTRACT

Juvenile myelomonocytic leukemia (JMML) is a hematologic malignancy of young children caused by mutations that increase Ras signaling output. Hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment, but patients with relapsed or refractory (advanced) disease have dismal outcomes. This phase II trial evaluated the safety and efficacy of trametinib, an oral MEK1/2 inhibitor, in patients with advanced JMML. Ten infants and children were enrolled, and the objective response rate was 50%. Four patients with refractory disease proceeded to HSCT after receiving trametinib. Three additional patients completed all 12 cycles permitted on study and continue to receive off-protocol trametinib without HSCT. The remaining three patients had progressive disease with two demonstrating molecular evolution by the end of cycle 2. Transcriptomic and proteomic analyses provided novel insights into the mechanisms of response and resistance to trametinib in JMML. ClinicalTrials.gov Identifier: NCT03190915.Significance: Trametinib was safe and effective in young children with relapsed or refractory JMML, a lethal disease with poor survival rates. Seven of 10 patients completed the maximum 12 cycles of therapy or used trametinib as a bridge to HSCT and are alive with a median follow-up of 24 months.See related commentary by Ben-Crentsil and Padron, p. 1574