Upper tract urothelial carcinoma (UTUC) affects 7,000 patients/year in the United States. Traditionally, the standard of care has been radical nephroureterectomy (RNU). A novel therapy using a mitomycin-containing thermagel, Jelmyto® (Urogen), has recently been approved for low-grade disease as adjuvant treatment provided as instillations into the kidney, for nephron preservation after endoscopic laser ablation. FDA approval was based on the OLYMPUS trial (71 patients, 24 centers, Lancet Oncology 2020) where the complete response (CR) rate for low-grade UTUC was 59%. However, a major concern when considering this therapy is the reported high adverse event (AE) rate of ureteral stenosis requiring stenting in 49% of patients, of which 15% had permanent stents. Our objective was to assess outcomes of Jelmyto therapy at a single center, with the goal to inform patients on what to expect regarding CR and AE rates.
We performed a retrospective review (IRB approved) of all patients with low-grade UTUC undergoing Jelmyto at Michigan Medicine between January 2021-July 2023. Following ureteroscopy and laser ablation in the operating room, instillations were performed in clinic under local anesthesia with either retrograde catheter or antegrade via nephrostomy by five providers. Patients underwent induction of six-weekly instillations and potential monthly maintenance instillations.
The mean age of patients was 69.3 years (range 52-84). Figure 1 demonstrates the patient flowchart. 20 patients received at least one dose of Jelmyto, of which 16 (80%) completed all six instillations. 12 patients (60%) had a CR after induction. Seven patients (35%) received at least one dose of monthly maintenance therapy, of which five demonstrated durability of response.
Six patients (30%) had an AE related to the urinary system. Ureteral stents were placed in five patients for ureteral stenosis (25%); of which four were transient, with no subsequent obstruction. Only one patient (5%) required permanent stenting.
In this early series from a single center, CR rates after induction with Jelmyto were similar to the OLYMPUS trial. However, ureteral stenosis requiring stenting was lower than previously reported. Future research is needed to determine what local factors are contributing to these results at our center.
Kleinmann, N., Matin, S. F., Pierorazio, P. M., Gore, J. L., Shabsigh, A., Hu, B., Chamie, K., Godoy, G., Hubosky, S., Rivera, M., O'Donnell, M., Quek, M., Raman, J. D., Knoedler, J. J., Scherr, D., Stern, J., Weight, C., Weizer, A., Woods, M., Kaimakliotis, H., … Lerner, S. P. (2020). Primary chemoablation of low-grade upper tract urothelial carcinoma using UGN-101, a mitomycin-containing reverse thermal gel (OLYMPUS): an open-label, single-arm, phase 3 trial. The Lancet. Oncology, 21(6), 776–785. https://doi-org.proxy.lib.umich.edu/10.1016/S1470-2045(20)30147-9
Figure 1: Patient flowchart demonstrating the outcomes of 20 patients receiving therapy with Jelmyto for upper tract urothelial carcinoma.