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Abstract: SA-PO215

Frequency and Characteristics of Chemotherapy-Associated Thrombotic Microangiopathy: Analysis from a Large Pharmacovigilance Database

Session Information

Category: Onconephrology

  • 1700 Onconephrology

Authors

  • Klomjit, Nattawat, Division of Nephrology and Hypertension, university of Minnesota, Minneapolis, Minnesota, United States
  • Evans, Rich, University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota, United States
  • Gupta, Shruti, Dana Farber Cancer Institute, Boston, Massachusetts, United States
Background

Thrombotic microangiopathy (TMA) is a rare but detrimental complication of chemotherapy. We examined the frequency and characteristics of chemotherapy-associated TMA using a large pharmacovigilance database.

Methods

We utilized Vigibase, a global drug monitoring database containing over 30 million adverse reports, to examine the frequency of TMA after each of these drug classes: immune checkpoint inhibitors (ICPi), proteasome inhibitors (PI), platinums, tyrosine kinase inhibitors (TKI)/vascular endothelial growth factors inhibitors (VEGFi), conventional chemotherapy (gemcitabine and mitomycin) and other conventional chemotherapy (bleomycin, docetaxel, pentostatin and doxorubicin). The strength of association was determined using information component (IC), a measure of disproportionality between the observed and expected number of reports for a drug-event combination. A positive IC indicates that the number of observed reports exceeds the number of expected reports. We also analyzed characteristics of individual cases who had TMA.

Results

Between 2010 and 2023, there were 4703 reports of chemotherapy-associated TMA in 1099 individuals. The drugs with the highest IC were carfilzomib (5.92), gemcitabine (5.52), mitomycin (4.22), bevacizumab (3.87) and bortezomib (3.69) (Figure 1). Among cases where only a single agent was used, TMA was most common with conventional chemotherapy (n=379, 41.2%) followed by PI (n=228, 24.8%), TKI/VEGFi (n=185, 20.1%), and platinums. Time to TMA onset was shortest in patients receiving other chemotherapy (31 days, IQR 30-34) and PI (35 days, IQR 8-178) and longest for conventional chemotherapy (156 days, IQR 91-245). Though uncommon, ICPI-associated TMA was associated with the highest mortality rate (41%).

Conclusion

The drugs most commonly associated with TMA were PI, TKI/VEGFi and conventional chemotherapy. Time to onset was shortest for patients receiving other conventional chemotherapy, while ICPi-TMA was associated with the highest mortality.