OBJECTIVES: To detect the possible safety signal of anti-neoplastic agents associated with Myelodysplastic Syndrome Transformation through disproportionality analysis in the FDA Adverse Event Reporting System (FAERS) Database.

METHODS: The case/non-case retrospective disproportionality analysis was performed in a publicly available FAERS database using OpenVigil 2.1(2014Q1-2022Q3). The preferred term defined by MedDRA v24 used for the study was ‘Myelodysplastic Syndrome Transformation’ and all anti-neoplastic drugs were screened for possible association with Myelodysplastic Syndrome Transformation. Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR) were used as the measure of disproportionality. The threshold for a positive signal was considered as ROR- 1.96SE>1 and PRR>2 with an associated chi-square value of 4 or more.

RESULTS: The FAERS database identified 366 cases of Myelodysplastic Syndrome Transformation, out of which 279(76.2%) were associated with anti-neoplastic agents. The maximum number of cases were associated with lenalidomide (n=127). Among the various anti-neoplastic drug classes, Pyrimidine antagonists accounted for 149 (33.71%), Immunomodulatory agents for 132 (29.86%), Purine antagonists for 42 (9.50%), Folate antagonists for 41 (9.27%), Anthracycline antibiotics for 37 (8.37%), Miscellaneous agents for 29 (6.56%), and Alkylating agents for 12 (2.71%) cases of Myelodysplastic Syndrome Transformation. The highest signal strength was found to be with arsenic trioxide (ROR 602.185) followed by azacytidine (ROR 382.349). On gender stratification, we found that the signal strength (ROR 57.11 and 37.239 respectively) was greater for females than males.

CONCLUSIONS: Our analysis of spontaneous reporting data identified signals for myelodysplastic syndrome transformation with antineoplastic drugs and more research with superior epidemiological studies is required to validate these findings.