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Abstract: PO2213

Cystatin C Measurement Improves Renal Function Estimation with Selpercatinib Use

Session Information

  • Onco-Nephrology - 2
    October 22, 2020 | Location: On-Demand
    Abstract Time: 10:00 AM - 12:00 PM

Category: Onco-Nephrology

  • 1500 Onco-Nephrology

Authors

  • Gutgarts, Victoria, Memorial Sloan Kettering Cancer Center, New York, New York, United States
  • Liu, Dazhi, 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
  • Drilon, Alexander, Memorial Sloan Kettering Cancer Center, New York, New York, United States
Introduction

Selpercatinib (LOXO-292) is a selective RET inhibitor that is approved for the treatment of RET-dependent lung and thyroid cancers. In the LIBRETTO-001 trial of selpercatinib, a treatment-emergent increase in serum creatinine was noted in ~18% of patients. Creatinine is mainly excreted by glomerular filtration and is partly secreted via transporters such as MATE-1. Inhibitors of MATE-1, such as selpercatinib, can reduce creatinine clearance leading to an incorrect diagnosis of drug related kidney injury. Cystatin C is an alternative marker that is freely filtered, completely reabsorbed and not secreted like creatinine. It is therefore not affected by transporter inhibitors and may be a better marker of kidney injury in patients receiving Selpercatinib. We present a patient on Selpercatinib with significant difference in kidney function by creatinine and cystatin C.

Case Description

58-year-old male with metastatic RET fusion-positive lung cancer who progressed on cabozantinib started selpercatinib. His pre-treatment creatinine was 0.8mg/dl and increased to 1.8mg/dl after 1 year of therapy. Urine sediment was bland with no significant proteinuria. Renal sonogram showed right sided hydronephrosis which prompted placement of ureteral stent. Creatinine did not improve with persistent hydronephrosis prompting conversion to a nephroureterostomy tube one year later. Creatinine remained elevated at 1.9mg/dl despite resolving hydronephrosis. Cystatin C levels were measured and showed significant discrepancy with serum creatinine as shown in Table below. This finding highlighted that although the patient did have chronic kidney disease, the extent was less than estimated by solely creatinine.

Discussion

This case highlights the benefit of checking both creatinine and cystatin C in patients on selpercatinib. Despite urological intervention, the persistence in elevated creatinine is likely attributed to the drug inhibitory effect on creatinine secretion. Cystatin C may be a better measure of renal function in patients receiving MATE-1 inhibitors such as selpercatinib.

Discrepancy in Serum Creatinine and Cystatin C Trends
Clinic EncountersCreatinine (mg/dL)GFR (mL/min/1.73m2)Cystatin C (mg/dL)GFR by Cystatin C (mL/min/1.73m2)
11.9381.262
22361.449
31.9381.261
41.455177