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Abstract: SA-PO117

Elevated Creatinine With Selpercatinib Therapy in RET-Dependent Malignancies

Session Information

Category: Onconephrology

  • 1600 Onconephrology

Authors

  • Gutgarts, Victoria, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Chen, Monica F., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Kaplanis, Lauren A., Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Harada, Guilherme, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Drilon, Alexander, Memorial Sloan Kettering Cancer Center, New York, New York, United States
Background

Selpercatinib (LOXO-292) is a novel selective RET inhibitor for RET-dependent malignancies. The adverse effect profile estimates ~9% elevated creatinine (Cr) after therapy initiation (Drilon et al, NEJM, 2020). Creatinine however may not be the best estimator of kidney function given selpercatinib is a MATE-1 inhibitor that may potentially lower tubular secretion of Cr. To date, there is no literature that describes Cr in these patients or the role of cystatin C (which is not secreted like Cr), as an alternative estimator of kidney function.

Methods

We retrospectively reviewed 94 patients at MSKCC initiated on selpercatinib. Baseline Cr was defined as Cr level prior to start of therapy. Creatinine levels that met criteria for acute kidney injury (AKI) (KDIGO stage 1: ≥1.5x but <2x baseline, stage 2: ≥2x but <3x baseline, stage 3 ≥3x baseline) at any point after start of therapy were recorded. Cystatin C data was recorded when available.

Results

11% (10/94) met criteria for AKI after selpercatinib initiation. The Figure below shows five patients had stage 1 (50%), 3 patients stage 2 (30%), and 2 patients stage 3 (20%) AKI. At 12 months Cr remained ≥0.5 in 2 patients (20%). Only 50% of patients had cystatin C levels checked and the Figure below shows that in the majority of cases, cystatin C is lower than Cr when checked at the same encounter. Two patients had kidney biopsies. Kidney biopsy for patient 6 showed acute tubular injury in the setting of diarrhea. Patient 9 had a kidney biopsy at an outside hospital that showed interstitial nephritis but details not known since he was lost to follow up.

Conclusion

As the use of selpercatinib grows in patients with RET-fusion malignancies, it is essential to better characterize the significance of elevated Cr findings. At this point, it is unclear if this is true AKI or elevated serum Cr due to inhibition of tubular Cr secretion. Prospective studies that involve Cr and simultaneous cystatin C should be performed to better estimate true kidney function in patients on selpercatinib.