DNA Damage Response Pharmacogenomic (DDR_PGx) Score Predicts Response to Chemotherapy Consisting of Gemtuzumab Ozogamicin in Pediatric AML: A Report from the Children’s Oncology Group

Shastri VM, Chauhan L, Gbadamosi M, Alonzo TA, Wang YC, Aplenc R, Hirsch BA, Kolb EA, Gamis AS, Meshinchi S, Lamba JK. DNA Damage Response Pharmacogenomic (DDR_PGx) Score Predicts Response to Chemotherapy Consisting of Gemtuzumab Ozogamicin in Pediatric AML: A Report from the Children’s Oncology Group. Clin Cancer Res. 2025 Mar 3;31(5):890-898. doi: 10.1158/1078-0432.CCR-23-2073. PMID: 38197878; PMCID: PMC11233425.

Comprehensive pharmacogenomics (PGx) evaluation of calicheamicin-pathway to identify predictive PGx markers of response to gemtuzumab ozogamicin (GO) treatment in acute myeloid leukemia (AML). Single nucleotide polymorphisms (SNPs) in DNA-damage response (DDR) pathway genes were tested for association with event-free survival (EFS), overall-survival (OS), risk of relapse after induction 1 (RR1) in patients treated with standard chemotherapy consisting of Ara-C, Daunorubicin and Etoposide (ADE) with or without addition of GO on COG-AAML03P1 and COG-AAAML0531 trials (ADE+GO, n=755; ADE n=470). SNPs with significant association with any endpoint within ADE+GO arm but not in the ADE arm were tested using multi-SNP modeling to develop DDR_PGx7 Score.