Session: 906. Outcomes Research—Malignant Conditions (Myeloid Disease): Poster I
Hematology Disease Topics & Pathways:
AML, Diseases, MDS, Adverse Events, Myeloid Malignancies
Methods: The FDA Adverse Events Reporting System (FAERS) database was queried for AEs associated with any of the 4 approved PARPi’s, from the date of the initial FDA approval for each agent (irrespective of the indication) through March 31, 2020. The FAERS database contains de-identified reports of product-related AEs, coded using the Medical Dictionary for Regulatory Activities (MedDRA) and classified as serious or non-serious. Cases reported outside the United States were excluded. The proportion of AML/MDS reports was analyzed overall and by PARPi. To account for the variation in length of time on the market due to the different approval dates, reports of AML/MDS for each PARPi were analyzed in the first 17 months after approval (the post-marketing period for the most recently approved agent). The indication for which the PARPi was used, the sex and age of the patient experiencing the AE, and the seriousness and outcome of the AE were assessed. Comparisons of the proportion of AML/MDS cases by agent were made using the Chi-square test; statistical significance was determined at a two-sided α=0.05.
Results: A total of 12823 post-marketing AE reports were associated with PARPi’s, with 88 (0.7%) reporting cases of AML/MDS (Table). The largest proportion of AML/MDS cases were associated with olaparib (54 of a total of 2121 AE reports; 2.5%, p<0.00001 vs. all other PARPi), followed by niraparib (23 of a total of 5879 AE reports; 0.4%) and rucaparib (11 of a total of 4707 AE reports; 0.2%). No AML/MDS cases were associated with talazoparib (0 of a total 116 AE reports). During the first 17 months following each agent’s approval, 14 cases of AML/MDS were reported in association with olaparib, 10 with rucaparib, 9 with niraparib, and 0 with talazoparib. The majority of cases of AML/MDS occurred in women (73%), and the most common indication for treatment was ovarian cancer (52%). The median age of the patients in the AML/MDS reports was 66 years. Nearly all cases were classified as serious (98%), and the outcome of the AE was death for 28% of cases, hospitalization for 17% of cases.
Conclusions: Our retrospective analysis found that AML/MDS associated with PARPi’s was reported rarely in the post-marketing setting, and that 60% involved olaparib. This study is limited by its retrospective design, and the possibility of under-reporting of cases to the FAERS database. Additionally, the time elapsed since approval differed by agent, and lower observed incidence of AML/MDS for some agents may reflect the limited duration of surveillance. No data is available in the case reports regarding length of exposure to chemotherapy. This real-world analysis complements existing clinical trial data and provides insight into AML/MDS associated with 4 different PARPi’s in clinical practice.
Disclosures: Gajra: Cardinal Health: Current Employment. Zettler: Cardinal Health: Current Employment. Klink: Cardinal Health: Current Employment. Feinberg: Cardinal Health: Current Employment.
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