Abstract: SA-PO117
Elevated Creatinine With Selpercatinib Therapy in RET-Dependent Malignancies
Session Information
- Onconephrology: Clinical and Research Advances - II
November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
Abstract Time: 10:00 AM - 12:00 PM
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.