Personalized Medicine in Infant Population with Cancer: Pharmacogenetic Pilot Study of Polymorphisms Related to Toxicity and Response to Chemotherapy.

Background: Pharmacogenetics is a personalized medicine tool that aims to optimize treatments by adapting them to each individual's genetics, maximizing their efficacy while minimizing their toxicity. Infants with cancer are especially vulnerable, and their co-morbidities have vital repercussions. The study of their pharmacogenetics is new in this clinical field.

Methods: A unicentric, ambispective study of a cohort of infants receiving chemotherapy (from January 2007 to August 2019). The genotypes of 64 patients under 18 months of age were correlated with severe drug toxicities and survival. A pharmacogenetics panel was configured based on PharmGKB, drug labels, and international experts' consortiums.

Results: Associations between SNPs and hematological toxicity were found. Most meaningful were: rs1801131 GT increasing the anemia risk (OR 1.73); rs1517114 GC, rs2228001 GT, increasing neutropenia risk (OR 1.50 and 4.63); rs1045642 AG, rs2073618 GG, rs4802101 TC and rs4880 GG increasing thrombocytopenia risk (OR 1.70, 1.77, 1.70, 1.73, respectively). Regarding survival, rs1801133 GG, rs2073618 GG, rs2228001 GT, rs2740574 CT, rs3215400 del.del, and rs4149015 GA were associated with lower overall survival probabilities (HR 3.12, 1.84, 1.68, 2.92, 1.90, and 3.96, respectively). Lastly, for event-free survival, rs1051266 TT and rs3215400 del.del increased the relapse probability (HR 1.61 and 2.19, respectively).

Conclusions: This pharmacogenetic study is a pioneer in dealing with infants under 18 months of age. Further studies are needed to confirm the utility of the findings in this work to be used as predictive genetic biomarkers of toxicity and therapeutic efficacy in the infant population. If confirmed, their use in therapeutic decisions could improve the quality of life and prognosis of these patients.